Universal Influenza Vaccine Technology Landscape

The Landscape is a database that compiles and summarizes publicly available information on the global R&D pipeline of universal, broadly protective, and next-generation influenza vaccine candidates, as defined in the Influenza Vaccines R&D Roadmap (IVR). Vaccine candidates profiled in the Landscape are designed to provide broader and more durable protection against seasonal and pandemic influenza, compared with current strain-specific influenza vaccines. 

CIDRAP initiated development of the Landscape with support from the Global Funders Consortium for Universal Influenza Vaccine Development (2019-2024) and currently receives support from the Collaborative Influenza Vaccine Innovation Centers (CIVICs), US National Institute of Allergy and Infectious Diseases (NIAID).

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Database last updated on Dec 21, 2024

Tracker

Vaccine Candidates 204 Vaccine Candidates
Vaccine in clinical trials 40 Vaccines in Clinical Trials
COVID+Flu Vaccine Candidates 5 COVID+Flu Vaccine Candidates
Developers 170 Developers
Platforms 6 Platforms
Preclinical 164
Phase 1 16
Phase 2 16
Phase 3 8
Approved 0

Database

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Influenza virus-based

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Nucleic acid-based

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Non-VLP nanoparticles

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Recombinant proteins

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Virus-like particles (VLP)

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Virus-vectored

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Vaccine Name Sort descending Developer / Location Platform Phase Approach & Sources

3M2e-3HA2-NP chimeric protein

Korea Research Institute of Bioscience and Biotechnology (Korea) Recombinant proteins Preclinical

Chimeric protein targeting M2e, HA and NP viral proteins; aimed at inducing influenza virus-specific antibody responses, cytotoxic T lymphocyte activity, and antibody-dependent cellular cytotoxicity.

3M2e-HA2-NP chimeric subunit

Pasteur Institute of Iran (Iran) Recombinant proteins Preclinical

Recombinant chimeric protein 3M2e-HA2-NP containing conserved regions of M2e, HA, and NP derived from influenza A virus.

3M2e-R4R5

University of Quebec at Montreal (Canada) Non-VLP nanoparticles Preclinical

An immunostimulating nanoparticle based on a fragment (R4R5) of the Curli-specific gene A (CsgA) protein that confers protection against influenza A virus when conjugated to three repeats of the highly conserved M2e epitope and administrated intranasally.

3M2e-rHF nanoparticle

Chinese Academy of Sciences (China) Non-VLP nanoparticles Preclinical

Tandem copies of M2e (3M2e) displayed on ferritin nanoparticles (recombinant human heavy chain ferritin, rHF); intranasal administration; aimed at stimulating cross-protective immunity through M2e-specific IgG antibodies, T-cell immune responses, and mucosal secretory-IgA antibodies.

3M2e-T4 nanoparticle

Huazhong Agricultural University (China) Non-VLP nanoparticles Preclinical

Insertion of Flu viral M2e into phage T4 genome through fusion to Soc (Small Outer Capsid protein) generated a recombinant phage, and the Soc-M2e proteins self-assembled onto phage capsids to form 3M2e-T4 nanoparticles during propagation of T4 in E. coli.

3MCD-f nanovaccine

Jilin University (China) Non-VLP nanoparticles Preclinical

Biepitope adjuvant-free, self-assembled influenza nanovaccine consisting of two conserved epitopes (M2e and CDhelix)

A/NP+M2-rAd

Food and Drug Administration (US) Virus-vectored Preclinical

Replication-deficient recombinant adenovirus-5 (rAd) vectors expressing conserved antigens NP and M2.

AAV‐vectored HA or cHA

Robert Koch Institute (Germany) Virus-vectored Preclinical

Adeno-associated virus (AAV) vectors expressing influenza virus HA or chimeric HA; aimed at inducing broadly protective antibodies.

Ace-DEX microparticle

University of North Carolina (US) Non-VLP nanoparticles Preclinical

M2e- and cyclic GMP-AMP (cGAMP)-encapsulated acetylated dextran (Ace-DEX) microparticles (MP); antigen-adjuvant combination is aimed at activation of humoral and cellular responses.

Ad-5-H1

Icahn School of Medicine at Mount Sinai (US), University of Maryland (US) Virus-vectored Preclinical

Non-replicating adenoviral (Ad) vector, encoding a secreted form of H1 HA, aimed at eliciting cross-reactive stalk-mediated cellular and humoral immunity and protection.

Ad4-H5-VTN

NIAID (US) Virus-vectored Phase 1

Replication-competent adenovirus type 4 encoding influenza virus H5 HA (Ad4-H5-Vtn) administered as an oral capsule or via tonsillar swab or nasal spray, as a potential platform for inducing durable and systemic mucosal immunity against influenza glycoproteins.

Goal
Next-generation influenza vaccine

AdC68-cHAs

Tianjin Medical University (China), Fudan University (China) Virus-vectored Preclinical

Novel cHAs comprising two or three fuzed head domains from different subtypes grafted onto one stalk domain, designated as cH1-H3, cH1-H7, cH1-H3-H7, and cH1-H7-H3

AdC68-CR9114

Fudan University (China) Virus-vectored Preclinical

Chimpanzee adenoviral vector, AdC68, expressing CR9114, a broadly neutralizing monoclonal antibody isolated form the peripheral blood mononuclear cells of healthy donors; CR9114 targets different types of influenza viruses.

Adjuvanted nanoparticle fusion constructs

Indian Institute of Science (India) Non-VLP nanoparticles Preclinical

Trimeric influenza stem domain immunogen, pH1HA10, displayed on the ferritin like protein MsDps2, Ferritin, and Encapsulin

AH3–GFP

Vaxsia Biomedical (Taiwan), University of Maryland Baltimore County (US) Non-VLP nanoparticles Preclinical

Self-assembled protein nanoparticle composed of a gain-of-function mutant of the AH3 peptide that enables temperature- and salt-dependent protein nanoparticle thermostability, intended to to stimulate a long-lasting humoral immune response, mediated by the presence of thermal stable protein nanoparticle that remains intact in the injection site

AP-M2e/tri-stalk VLP

Latvian Biomedical Research and Study Centre (Latvia) Virus-like particles (VLP) Preclinical

Panel of constructs based on HA tri-stalk and triple M2e (3M2e) antigens integrated into a bacteriophage AP205 VLP platform; aimed at broad protection against seasonal and novel influenza strains.

B60-Stem-8071

Xiamen University (China) Recombinant proteins Preclinical

 

An HA stem vaccine grafted with an epitope of broadly neutralizing antibodies CR8071 to stabilize the stem HA domain

BP-NP366/PA224

University of Melbourne (Australia), Griffith University (Australia) Non-VLP nanoparticles Preclinical

Endotoxin-free production strain of E. coli bioengineered to assemble biopolymer particles (BPs) coated with conserved influenza antigens (BP-NP366/PA224).

BP26-M2e nanobarrels

Korea Advanced Institute of Science and Technology (Korea) Non-VLP nanoparticles Preclinical

Engineered monomeric BP26 monomers bearing an antigen aimed at promoting antigen-specific antibody production.

BPL-1357

NIAID (US) Influenza virus-based Phase 1

BPL-1357 contains 4 whole inactivated avian influenza virus strains: H7N3, H5N1, H3N8, and H1N9; administered either intranasally or intramuscularly; intended to induce mucosal immunity similar to the immune response following influenza infection including cellular and B cell responses.

Goal
Universal or broadly protective influenza vaccine

Cap-Cat VLPs

Henan Academy of Agricultural Sciences (China), Zhengzhou University (China) Virus-like particles (VLP) Preclinical

A generalized nanoantigen display platform, Cap-Cat virus-like particles (VLPs) displaying antigens such as M2e; aimed at providing cross-protection against diverse subtypes of influenza A virus strains.

Formerly: Cap-M2e VLP

CapM2e+Advax-SM

Vaxine (Australia) Recombinant proteins Preclinical

M2e antigen based vaccine formulated with Advax-SM adjuvant administered to mothers aimed at inducing passive maternal protection to newborns

CDh-f nanoparticle

Jilin University (China) Non-VLP nanoparticles Preclinical

The A helix (Ah) and CD helix (CDh) from the HA stem were fused with ferritin, individually, or in tandem, yielding Ah-f, CDh-f and (A + CD)h-f nanoparticles (NPs), produced through a prokaryotic expression system.

cGAMP-adjuvanted multivalent mRNA vaccines

Georgia State University (US) Nucleic acid-based Preclinical

A multivalent influenza mRNA lipid nanoparticle (LNP) vaccine with mRNAs of hemagglutinins from influenza H1N1 and H3N2 viruses, matrix protein 1, and nucleoprotein, adjuvanted with cGAMP

ChAdOx1 NP+M1 and MVA NP+M1 in heterologous prime-boost regimens

Jenner Institute, University of Oxford (UK) Virus-vectored Phase 1

Two-dose heterologous viral vectored constructs: modified vaccinia virus Ankara (MVA) and the chimpanzee adenovirus ChAdOx2 expressing conserved influenza virus antigens, nucleoprotein (NP) and matrix protein-1 (M1); aimed at stimulating T-cell responses to influenza virus.

Goal
Universal or broadly protective influenza vaccine

ChAdOx2-NPM1-NA2 and MVA-NPM1NA2

Pirbright Institute (UK) Virus-vectored Preclinical

Aerosol immunization with viral vectored vaccines (ChAdOx2 and MVA) expressing matrix (M1) and nucleoprotein (NP)

cHAmg

Academia Sinica (Taiwan), Scripps Research Institute (US), National Yang-Ming University (Taiwan) Recombinant proteins Preclinical

Monoglycosylated chimeric HA (cHAmg) with consensus H5 head and consensus H1 stem antigens or C34-adjuvanted monoglycosylated HA stem (HA stemmg); aimed at eliciting high titers of cross-reactive antibodies against a range of influenza strains and subtypes through CD4+ and CD8+ T cell responses.

Chimeric cytokine HA-VLP vaccine

Nerome Institute of Biological Resources (Japan) Virus-like particles (VLP) Preclinical

VLPs containing a chimeric cytokine (CC) comprising the M2 protein, influenza A neuraminidase stalk

Chimeric HA constructs

Icahn School of Medicine at Mount Sinai (US) Influenza virus-based Phase 2

Sequential combinations of different platforms, including LAIVs and inactivated split vaccines, with adjuvants, or of chimeric (cHA) or mosaic (mHA) constructs (cHA-LAIV-LAIV and cHA-LAIV-IIV, M2e), consisting of “exotic” HA head domains (from avian influenza viruses) and a conserved stalk domain; sequential administration with cHAs with different head domains and the same stalk domain; aimed at focusing humoral immunity on the highly conserved HA stalk domain.

(Formerly: cHA-based LAIV combinations)

Goal
Universal or broadly protective influenza vaccine

Dong and Wang 2024 (PMID: 38788629), Bliss 2024 (PMID: 38805853), Edgar 2023 (PMID: 37871218), Puente-Massaguer 2023 (PMID: 37703367), Puente-Massaguer 2023 (PMID: 37342504), Meade 2022 (PMID: 36533948), Aydillo 2022 (PMID: 36496417), Zhu 2022 (PMID: 35594401), Isakova-Sivak 2022 (PMID: 35461523), Folschweiller 2022 (PMID: 35461522), Guthmiller 2021, Nachbagauer 2021 (PMID: 33288923), Liu 2021 (PMID: 33440898), Bernstein 2020 (PMID: 31630990), Destexhe 2020 (PMID: 32119974), Broecker 2019 (PMID: 31341648), Sun 2019 (PMID: 31540436), Krammer 2019 (PMID: 30715353), Nachbagauer 2019 (PMID: 31839997), Liu 2019 (PMID: 31105689), Choi 2019 (PMID: 31032479), Sunwoo 2018 (PMID: 30223475), Nachbagauer 2018 (PMID: 30044403), Nachbagauer 2017 (PMID: 29263881), Nachbagauer 2016 (PMID: 26719251), EudraCT: 2017-001584-20 (P1/2), NCT03275389 (P1), NCT03300050 (P1), NCT02415842 (Observational), Press Release 6-30-2022, Press Release 7-16-2020, Press Release 12-7-2020, Press Release 5-1-2019, News Story 12-7-2020, NIH Funding

Chimeric M2e nanoassemblies

University of Quebec at Montreal (Canada) Non-VLP nanoparticles Preclinical

Nanofibril-based construct using a chimeric M2e peptide.

CIC Vaccine

Novavax (US) Non-VLP nanoparticles Phase 3

Combination SARS-CoV-2 (COVID-19) and influenza vaccine that uses full-length, stabilized recombinant spike (rS) protein of the SARS-CoV-2 virus, and 4 wild-type recombinant Hemagglutinin (rHA) proteins from the influenza virus, as antigens.

Goal 
Next-generation combination COVID + influenza vaccine

Clec9A-M2e

National University of Singapore (Singapore), Monash University (Australia) Recombinant proteins Preclinical

Targeting strategy that shuttles M2e to a specific dendritic cell subset (cDC1) by engineering a recombinant anti-Clec9A monoclonal antibody fused at each of its heavy chains with three copies of M2e

COBRA H1 HA

University of North Carolina (US), University of Georgia (US) Recombinant proteins Preclinical

COBRA HA vaccine coadministered intranasally with a novel adjuvant. Adjuvants include PEI-Ox-DEX hydrogel, M7-CpG, and cGAMP MPs

COBRA HA and NA proteins

University of Georgia (US) Recombinant proteins Preclinical

Multivalent COBRA (computationally optimized broadly reactive antigens) HA and NA immunogens (N1 and N2) designed to cross react with several IAV strains, adjuvanted with Advax-SMTM, a novel adjuvant comprising inulin polysaccharide and CpG55.2, a TLR9 agonist, or with c-di-AMP adjuvant.

COBRA HA-encoding mRNA

University of Georgia (US) Nucleic acid-based Preclinical

mRNA encoding H1 and H3 COBRA hemagglutinins (HA) or wild-type (WT) influenza HAs encapsulated in lipid nanoparticles (LNPs)

COBRA-VLP

University of Georgia (US), Cleveland Clinic (US) Virus-like particles (VLP) Preclinical

VLP constructs expressing COBRA (computationally optimized broadly reactive antigens) for HA or NA (specifically N2 NA); aimed at eliciting high-titer broadly cross-reactive neutralizing antibodies to multiple HA epitopes on antigenically distinct influenza viruses.

CodaVax

Codagenix (US) Influenza virus-based Phase 1

LAIV generated through synthetic attenuated virus-engineering (SAVE); uses an algorithm to “de-optimize” the influenza HA and NA gene segments for reduced translation in human cells, resulting in virus attenuation while preserving the immunogenicity of wild-type virus; aimed at stimulating an immune response against influenza viruses from multiple seasons and multiple decades (e.g. influenza viruses from 1970s and 1930s).

Goal
Universal or broadly protective influenza vaccine

Combinatorial polymeric nanoshell

National Taiwan University (Taiwan) Non-VLP nanoparticles Preclinical

Nanoshell vaccine with co-encapsulation of peptides aimed at inducing a T cell response.

Conjugate vaccine and P8 carrier peptide

TRIA Bioscience (US) Non-VLP nanoparticles Preclinical

Nanoparticle-based peptide containing the highly conserved alpha-helical domain within the influenza HA stem (peptides modified with the Helix A epitope); GLA-SE adjuvanted and aimed at inducing functional antibodies to small molecules and protein-based epitopes.

Conjugated HA stem

University of Melbourne (Australia) Recombinant proteins Preclinical

Chemically coupled peptide derived from head domain of PR8 HA with HA stem protein.

CTA1-3M2e-DD (FPM2e)

University of Gothenburg (Sweden), Ghent University (Belgium) Non-VLP nanoparticles Preclinical

Combined M2e-based fusion protein with a cholera toxin-derived adjuvant (CTA1-DD) and lipid nanoparticles; aimed at enhancing anti-M2e antibodies and CD4+ T cell responses.

ctLAIV

Yonsei University (South Korea) Influenza virus-based Preclinical

Caspase-triggered live attenuated influenza vaccine (ctLAIV), which is self-attenuated by the host caspase-dependent cleavage of internal viral proteins.

cVLPs

Jiaxing University (China) Virus-like particles (VLP) Preclinical

The conserved stalk domain and 4M2e co-anchored to the surface particles to generate chimeric influenza VLPs aimed at inducing humoral and mucosal immune responses.

cVLPs

University of Copenhagen (Denmark), Scripps Research Institute (US) Virus-like particles (VLP) Preclinical

Recombinant vaccine antigens (HAstem or rNA) displayed on the surface of rigid capsid-based virus-like particles (cVLP).

(formerly: CLP-HAstem)

CyCMV/Flu

Oregon Health & Science University (US) Virus-vectored Preclinical

Cytomegalovirus (CMV)-vectored vaccine (CyCMV)  expressing conserved internal influenza antigens (M1, NP, and PB1), aimed at inducing lung-resident influenza-specific CD4+ T cells to provide long-lived heterosubtypic protection.

dbDNA-encoded NA

Imperial College London (UK) Nucleic acid-based Preclinical

Influenza virus vaccines made using a closed linear DNA platform, Doggybone™ DNA (dbDNA), produced by a rapid and scalable cell-free method and encoding NA

DCVC H1 HA mRNA-LNP

NIAID (US) Nucleic acid-based Phase 1

An mRNA encoding the full-length HA of influenza A/California/07/2009 (H1N1).

Goal 
Next-generation influenza vaccine

Deglycosylated modified HA

Xiamen University (China) Recombinant proteins Preclinical

 

Deglycosylated modified HA proteins from H3N2 with various lengths of glycans administered intramuscularly

deltaFLU

Vivaldi Biosciences (US) Influenza virus-based Phase 2

Self-adjuvanted, nonstructural protein 1 (NS1)-deficient, replication-deficient LAIV; administered as a nasal spray; aimed at stimulating interferon, mucosal cross-neutralizing IgA antibodies, systemic cytotoxic T-cell response (Th1) and B-cell response with cross-neutralizing antibodies and memory T-cell response.

Goal
Universal or broadly protective influenza vaccine

DNA constructs with plasmids encoding conserved antigens

State Research Center of Virology and Biotechnology (Russia) Nucleic acid-based Preclinical

DNA encoding artificial antigens based on the HA stalk and M2 protein to induce cross-protective humoral and cell-mediated responses.

DNA prime-subunit protein boost

Shanghai Institute of Biological Products (China) Nucleic acid-based Preclinical

DNA plasmid encoding conserved M1 (prime) and soluble recombinant M1 subunit protein (boost); aimed at inducing cellular and humoral immune responses for cross protection against heterosubtypic virus infection.

Double-layered protein nanoparticles

Georgia State University (US) Non-VLP nanoparticles Preclinical

Layered protein nanoparticles expressing multivalent conserved antigens (M2e, NP, HA stem domains); conjugated with truncated flagellin (tFliC); aimed at inducing broadly cross-protective immune responses.

Status: Active

EBS-UFV-001 (UFluA)

Emergent BioSolutions (US) Non-VLP nanoparticles Phase 1

Nanoparticle based vaccine that self-assembles during production and that displays a cross-reactive HA antigen for influenza virus A groups 1 and 2. The self-assembling HA stabilized stem nanoparticle technology was developed by and licensed from NIAID. UFluA is comprised of DP-UFluA (1:1 A1-ssnp and A2-ssnp antigens) and contains aluminum hydroxide and CpG adjuvants.

Goal
Universal or broadly protective influenza vaccine

EFn-3xM2e-HA2+PA

Texas Tech University (US) Recombinant proteins Preclinical

Antigen consisting of 3 tandem M2e repeats plus HA2, in combination with a detoxified anthrax edema toxin (EFn plus PA); aimed at eliciting antigen-specific IgG responses; administered intranasally.

Epigraph HA

University of Nebraska−Lincoln (US) Virus-vectored Preclinical

Vaccine designed using the Epigraph vaccine antigen designer, which uses a graph-based algorithm to create vaccine antigens with maximized potential epitope coverage of a highly diverse sequence population. For example, a universal swH3 vaccine by computationally designing a cocktail of three swH3 hemagglutinins (HA), or immunogens designed against the HA protein of IBV (IBV-Epi).

fH1/DSP-0546LP

Sumitomo Pharma (Japan), National Institutes of Biomedical Innovation, Health and Nutrition (Japan) Recombinant proteins Phase 1

Post-fusion HA antigens adjuvanted with a newly developed liposomal SA-2 containing a synthetic toll-like receptor (TLR) 7 agonist (DSP-0546) compound.

Goal
Universal or broadly protective influenza vaccine

FLU-v

ConserV Bioscience (UK), Imutex (UK) Recombinant proteins Phase 2

Peptide-based construct derived from conserved regions of internal proteins (M1, IAV-NP, IBV-NP, and M2) aiming to provide a broadly protective immune response against influenza A and B through viral clearance by cytotoxic T cell responses.

Goal
Universal or broadly protective influenza vaccine

FluMos self-assembling nanoparticle

NIAID (US) Non-VLP nanoparticles Phase 1

Uses computationally designed nanoparticle immunogens that controllably display diverse HA trimers in an ordered array on self-assembling protein nanoparticles; aimed at eliciting both HAI activity and protective stem-directed neutralizing antibodies against heterosubtypic influenza viruses.

(Formerly: FluMos-v1)

Goal
Universal or broadly protective influenza vaccine

FP-01.1

Immune Targeting Systems (now Altimmune) (US) Recombinant proteins Phase 2

Novel construct consisting of 6 synthetic peptides linked to an inert fluorocarbon chain, encapsulating multiple conserved epitopes (NP, M, and PB1/PB2); aimed at generating T cell responses to divergent influenza strains.

Goal
Universal or broadly protective influenza vaccine

G1 mHA

Janssen Vaccines and Prevention, J&J (Netherlands) Recombinant proteins Phase 2

Group 1 HA stem-based antigen, based on an approach that removes the immunodominant HA head region while stabilizing the structure of the stem region; aimed at inducing broadly neutralizing antibodies.

(Formerly: Mini-HA)

Goal
Universal or broadly protective influenza vaccine

GammaFlu

Gamma Vaccines (Australia) Influenza virus-based Preclinical

Whole influenza virus inactivated with gamma irradiation to prevent viral replication, leaving the external and internal protein antigens intact; aimed at stimulating antibodies and cytotoxic T-cells to provide cross-protective immunity; intranasal administration.

H1, H3 COBRA IIV

University of Georgia (US), Cleveland Clinic (US) Influenza virus-based Preclinical

Reassortant influenza viruses expressing H1 and H3 computationally optimized broadly reactive antigens (COBRA) HA antigens.

H1-based cHAs

University of Ghana (Ghana) Recombinant proteins Preclinical

Chimeric HAs (cHAs) generated with consensus sequence building aimed at inducing cross-reactive antibodies.

H1c-mRNA-LNP

National Engineering Technology Research Center for Combined Vaccines (China) Nucleic acid-based Preclinical

A lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA vaccine (mRNA-LNPs) that encodes a consensus full-length HA sequence (H1c)

H2-CON

University of Nebraska−Lincoln (US) Virus-vectored Preclinical

Adenoviral-vectored centralized consensus HA construct against H2 influenza A virus, designed to induce broadly protective antibody titers when delivered in a prime-boost strategy first by Ad6 and followed with Ad5.

H3N1M2e5x VLP

Kyung Hee University (S Korea) Virus-like particles (VLP) Preclinical

Influenza VLPs expressing hemagglutinin (HA) subtypes (H1, H3, H5) with or without a combination of the following: NA, avian NA subtypes (N1, N6, N8), or M2e5x.

(Formerly: VLPs)

H3N8 live attenuated virus vaccine

Iowa State University (US) Influenza virus-based Preclinical

Live attenuated equine influenza virus (LAIV) equine H3N8 vaccine to induce broad protection without the need for non-influenza viral vectors, multiple HAs, or foreign protein scaffolds common to other universal influenza vaccine candidates.

HA trimers

California Institute of Technology (US) Non-VLP nanoparticles Preclinical

Uses the SpyCatcher-SpyTag “plug and display” strategy to covalently couple trimeric HAs to symmetric particles with different numbers of attachments sites, resulting in mosaic particles displaying HA antigens derived from up to 8 strains of group 1 and group 2 influenza A viruses.

HA, NP, and 3M2e mRNA

Chinese PLA General Hospital (China) Nucleic acid-based Preclinical

mRNA vaccine encoding influenza hemagglutinin (HA), nucleoprotein (NP), and three tandem repeats of matrix protein 2 (3M2e).

HA-clamp proteins

University of Queensland (Australia) Recombinant proteins Preclinical

Molecular clamp which utilizes the highly stable trimerization domain to allow for efficient production and purification of conformationally stabilized perfusion hemagglutinin HA

HA-encoding mRNA

University of Georgia (US) Nucleic acid-based Preclinical

Novel quadravalent mRNA influenza vaccine encoding hemagglutinin (HA) proteins.

HA-F DNA vaccine

Jilin University (China) Nucleic acid-based Preclinical

A DNA vaccine designed by fusing influenza virus HA with self-assembled ferritin nanoparticles aimed at providing robust immunogenicity, high protective efficacy and being an effective vaccine with rapid production

HA-liposomes

Monash University (Australia) Non-VLP nanoparticles Preclinical

Production of lipid nanoparticle subunit vaccines with HA immunogens functionalized on the surface of the liposomes; uses advanced microfluidic mixing technology (NanoAssemblr) to enable rapid preparation of liposomal vaccines with increased concentrations of HA antigens on the liposome surface; aimed eliciting HA-specific B cell and follicular helper T cell immune responses.

HA-SAV

Yonsei University (South Korea) Non-VLP nanoparticles Preclinical

A self-assembled vaccine (SAV) platform comprising antigen-polymer conjugates to elicit enhanced immune responses against pathogen

HA-T-AGM Protein

Translational Health Science & Technology Institute (India) Recombinant proteins Preclinical

A recombinant full-length soluble trimeric HA protein expressed in mammalian Expi293F expression system administered intradermally and with Addavax adjuvant

HA-VLP-Cyt

Georgia State University (US) Virus-like particles (VLP) Preclinical

Cytokine-adjuvanted influenza hemagglutinin virus-like particles (HA-VLP) vaccine aimed at inducing cellular and humoral immunity

HA/GP nanoparticles

Georgia State University (US) Non-VLP nanoparticles Preclinical

Polyethyleneimine-functionalized graphene oxide nanoparticles (GP nanoparticles); administered intranasally; aimed at enhancing HA immunogenicity

HA2 HA-ferritin nanoparticle

NIAID (US) Non-VLP nanoparticles Phase 1

Ferritin nanoparticle vaccine composed of the ectodomain of the HA from the H2N2 pandemic strain A/Singapore/1/57 genetically fused to the ferritin subunit derived from Helicobacter pylori that displays eight antigenically intact influenza H2 HA trimers in an orderly array on the nanoparticle surface

Goal
Universal or broadly protective influenza vaccine

HAd-C5-NP(H7N9)

Purdue University (US) Virus-vectored Preclinical

A mucosal Ad vector-based vaccine expressing NP, from an H7N9 influenza virus, with AIP-C5, an autophagy-inducing peptide (AIP) aimed at enhancing T cell immune responses.

HAm

Sun Yat-sen University (China) Recombinant proteins Preclinical

Stabilized trimeric recombinant mosaic HA proteins named HAm, expressed using a protein-based vaccine platform

HAsd protein

Southwest Jiaotong University College of Medicine (China) Recombinant proteins Preclinical

Recombinant protein based construct targeting the HA stalk domain (HAsd) displayed on the surface of L. lactis; aimed at providing cross-immunity against divergent influenza A viruses.

HBc VLPs

Chinese Academy of Sciences (China) Virus-like particles (VLP) Preclinical

Biomimetic dual-antigen hybrid nanovaccine VLP construct with interior NP and exterior M2e antigens, using a hepatitis B virus core (HBc) VLP; aimed at inducing a cross-protective immune response.

Helix-A stem nanoparticle

NIAID (US) Non-VLP nanoparticles Preclinical

Nanoparticle-based vaccine that displays multiple copies of the conserved influenza helix-A region per nanoparticle subunit

Hexaplex liposomes

State University of New York at Buffalo (US) Non-VLP nanoparticles Preclinical

Recombinant HA and NA multimeric proteins derived from three influenza serotypes, H1N1, H3N2, and type B, are surface displayed on nanoliposomes co-loaded with immunostimulatory adjuvants, generating "hexaplex" particles 

hlHA IIV

Duke University (US) Influenza virus-based Preclinical

Authentic influenza A virus (IAV) particles that harbor “headless” HA (hlHA) along with the normal complement of other viral proteins to serve as an inactivated influenza vaccine (IIV)

Hybrid fusion protein combination vaccine

Emory University (US), Georgia State University (US) Virus-like particles (VLP) Preclinical

Combination influenza and SARS-CoV-2 (COVID-19) VLP vaccine that uses influenza virus-like particles (VLP) incorporated by protein transfer with glycosylphosphatidylinositol (GPI)-anchored SARS-CoV-2 RBD fused to GM-CSF as an adjuvant

IA-SNBs

NIAID (US) Non-VLP nanoparticles Preclinical

HA complexes arranged as lipid discs with multiple trimeric HAs displayed along the perimeter, termed spike nanobicelles (SNB), used to synthesize in vitro assembled spiked nanobicelles (IA-SNB) from a classical 1934 H1N1 influenza virus.

IAV NP mRNA/DDO268

Washington University (US) Nucleic acid-based Preclinical

Viral-derived oligonucleotides (DDO) adjuvanted mRNA vaccine encoding the IAV NP

IAV-nanovax

University of Iowa (US), Iowa State University (US) Non-VLP nanoparticles Preclinical

Combination nanovaccine platform based on pentablock copolymer micelles and polyanhydride nanoparticles, incorporating the hemagglutinin (HA) and nucleoprotein (NP) antigens from H1N1; aimed at boosting cell-mediated immune responses.

Status: Active

Intranasal NLP:NP

University of Rochester Medical Center (US) Non-VLP nanoparticles Preclinical

Self-assembling nanolipoprotein particle linked to NP with an adjuvant

Inverted HA VLP

Georgia Institute of Technology (US), Icahn School of Medicine at Mount Sinai (US) Virus-like particles (VLP) Preclinical

A VLP that displays multiple copies of an antigen binding fragment (Fab) which recognizes the apex of the HA head causing the subsequent binding of HA to result in its presentation in an inverted orientation.

ISCOMs/MPLA-adjuvanted SDAD protein nanoparticles

Georgia State University (US) Non-VLP nanoparticles Preclinical

A core/shell protein nanoparticle consisting of influenza nucleoprotein (NP) as the core and NA1-M2e or NA2-M2e fusion proteins as the coating antigens by SDAD hetero-bifunctional crosslinking boosted by immune-stimulating complexes (ISCOMs)/monophosphoryl lipid A (MPLA) adjuvants

LAIV+4M2e

Institute of Experimental Medicine (Russia) Influenza virus-based Preclinical

Recombinant LAIV expressing additional 4 M2e tandem repeats (4M2e); aimed at enhancing M2e-mediated cross-protection against heterologous viruses.

LHNVD-105

Longhorn Vaccines and Diagnostics (US) Recombinant proteins Preclinical

Multi-epitope unconjugated and CRM-conjugated peptides targeting HA, NA and M2e; formulated with ALFQ (Army liposomal) adjuvant

Liposomal peptide vaccine

Griffith University (Australia) Non-VLP nanoparticles Preclinical

Liposomal vaccine adjuvanted with the TLR4 agonist, 3D-PHAD, and express the conserved influenza A M2e epitope

m-cNA-M2e VLP

Georgia State University (US) Virus-like particles (VLP) Preclinical

A single entity of VLP displaying consensus multi-neuraminidase (NA) subtypes (cN1, cN2, BcNA) and M2 ectodomain (M2e) tandem repeat (mcNA-M2e VLP) administered intramuscularly.

M2 peptide micelles

University of Missouri (US) Non-VLP nanoparticles Preclinical

Immunostimulatory micellar nanoparticles generated from M22–16 peptides by lipid conjugation 

M2e based recombinant fusion proteins

Russian Ministry of Health (Russia) Recombinant proteins Preclinical

Recombinant plant-produced protein (Flg4M2eHA2-1) based on the combination of 4 tandem copies of M2e and conserved fragments of HA2, fused to bacterial flagellin containing CD8+ epitopes of NP as an adjuvant for mucosal immunization; administered intranasally.

M2e Nanoclusters

Texas Tech University (US), Georgia State University (US) Non-VLP nanoparticles Preclinical

Unadjuvanted cross linked M2e nanoclusters (NCs)

Status: Active

M2e VLP

Russian Academy of Sciences (Russia), VA Pharma (Russia) Virus-like particles (VLP) Phase 1

Recombinant VLPs displaying multiple copies of M2e aimed at inducing M2e-antibody responses.

(Formerly: HBc-4M2eh (Uniflu))

Goal
Universal or broadly protective influenza vaccine

M2e VLP MP

Mercer University (US) Virus-like particles (VLP) Preclinical

Adjuvanted M2e based VLP encapsulated into a micro particulate matrix

M2e-based self-assembled nanoparticle

Fudan University (China) Non-VLP nanoparticles Preclinical

M2e epitope-bearing self-assembling nanoparticles that aim to induce antibodies against M2e on different influenza subtypes.

M2e-CRM197 conjugates

Chinese Academy of Sciences (China) Recombinant proteins Preclinical

Dual-site specific conjugation of M2e peptide with the CRM197 carrier protein under denaturation.

M2e-H3 stalk

Georgia State University (US) Recombinant proteins Preclinical

Chimeric M2e and H3 hemagglutinin (HA) stalk protein vaccine engineered by genetically linking M2e repeat to the engineered H3 stalk domain with stabilizing HA1 N- and C-terminal region and point mutations

M2e/CpG-ODN/TMC

Agricultural Research, Education and Extension Organization (Iran) Non-VLP nanoparticles Preclinical

Nasal vaccination with the M2e/CpG-ODN antigen encapsulated in N-Trimethyl Chitosan (TMC) nanoparticles

M2SR

FluGen (US) Influenza virus-based Phase 2

Novel single-replication (SR) platform for influenza A or B virus based on an otherwise wild-type influenza virus that does not express the M2 ion channel protein (M2-deficient); administered intranasally; aimed at eliciting cross-reactive antibodies against conserved HA stem and systemic and mucosal immune responses that block virus replication in the lung and provide cross-lineage protection against influenza virus. Quad M2SR, a quadrivalent form of this vaccine candidate, is currently in preclinical development.

Goal
Universal or broadly protective influenza vaccine

Hatta 2024 (PMID: 39591131), Hill-Batorski 2024 (PMID: 39012796), Sambhara 2024 (PMID: 39004095), Eiden 2024 (PMID: 39004096), Hill-Batorski 2023 (PMID: 37112710), Eiden 2023 (PMID: 36350017), Sarwar 2022 (PMID: 36560540), Eiden 2022 (PMID: 34323977), Eiden 2021, Moser 2019 (PMID: 31280945), Hatta 2018 (PMID: 30007825), Hatta 2017 (PMID: 28668565), Sarawar 2016 (PMID: 27595896), Hatta 2011 (PMID: 21272601), Watanabe 2009 (PMID: 19321619), News story 8-15-2024, Press Release 7-12-2024, News story 10-3-2022, Press release 11-9-2022, Press release 9-7-2022, Press Release 8-1-2022, Press Release 7-27-2022, Press release 6-22-2022, Press release 8-2-2021, Press Release 7-1-2021, Press release 5-25-2021, Press Release 8-28-2019, EudraCT 2017-004971-30 (P2a), NCT04960397 (P1b), NCT05163847 (P1b), NCT04785794 (P1b), NCT03553940 (P1), NCT03999554 (P1), NCT02822105 (P1), Developer website

MAV-1 HA

University of Liège (Belgium) Virus-vectored Preclinical

Recombinant mouse adenovirus (AdV) type 1 (MAV-1) expressing the HA of PR8, administered orally

mHAs

Chinese Academy of Sciences (China) Nucleic acid-based Preclinical

mRNA vaccine (mHAs) encoding the HA stem antigen of the influenza A (H1N1) virus.

Micro-consensus DNA vaccine

Wistar Institute (US), Inovio Pharmaceuticals (US) Nucleic acid-based Phase 1

Synthetic microconsensus DNA platform based on 4 plasmid-encoding microconsensus H1 and H3 HA antigens, each containing a limited consensus sequence based on analysis of a subset of primary sequences of H1 and H3 HA antigens; aimed at inducing protective levels of HAI titers to diverse isolates of H1N1 and H3N2 influenza; delivered by intradermal/intramuscular electroporation (EP); aimed at eliciting antibody and T-cell responses.

Goal
Universal or broadly protective influenza vaccine

Mini-HA-LS Nano-vaccine

Huazhong Agricultural University (China) Non-VLP nanoparticles Preclinical

Mini-HA proteins expressed on lumazine synthase (LS) nanoparticles by SpyTag/SpyCatcher aimed at eliciting potent immune responses

MLN-mRNA

Shanghai Institute of Biological Products (China) Nucleic acid-based Preclinical

A novel mRNA-based multiantigen influenza vaccine based on a single mRNA molecule with a tandem of three conserved antigens of influenza A virus, including the ectodomain of the M2 ion channel (M2e), the long alpha helix of haemagglutinin stalk region (LAH), and nucleoprotein (NP)

Modified mRNA vaccine

Pfizer (US) Nucleic acid-based Phase 3

Next generation mRNA seasonal influenza vaccine encoding WHO recommended strain

Goal 
Next-generation influenza vaccine

modRNA-based combination

Pfizer (US), BioNTech (Germany) Nucleic acid-based Phase 3

Combination mRNA SARS-CoV-2 (COVID-19) and influenza vaccine containing mRNA strains encoding the wild-type spike protein of SARS-CoV-2 and the spike protein of the Omicron BA.4/BA.5 subvariants as well as mRNA strands encoding the hemagglutinin of four different influenza strains

Goal 
Next-generation combination COVID + influenza vaccine

Monovalent rNA

Sanofi (France) Recombinant proteins Preclinical

A rNA monovalent protein vaccine candidate vaccine that uses tetramer conformation to enable stability for at least 24-months at refrigerated (5°C) storage.

Mosaic and Chimeric HA

Icahn School of Medicine at Mount Sinai (US) Recombinant proteins Preclinical

Novel constructs of recombinant mosaic and chimeric HA, expressed as soluble trimeric proteins; aimed at inducing broadly protective immune responses to influenza A and B strains.

Mosaic HA-based whole inactivated virus

Icahn School of Medicine at Mount Sinai (US) Influenza virus-based Preclinical

Activated influenza B viruses displaying mosaic HA (mHA) proteins to redirect the immune response towards the immuno-subdominant conserved epitopes of the HA.

Mosaic NA1 (mNA1)

Sun Yat-sen University (China) Nucleic acid-based Preclinical

A series of genetic algorithm-based mosaic NA1 (mNA1) designed, then cloned into recombinant DNA and replication-defective Vesicular Stomatitis Virus (VSV) vector

Mosaic VLPs

Sun Yat-sen University (China) Virus-like particles (VLP) Preclinical

An HA and NA mosaic immunogen cocktail containing the majority of potential T-cell epitopes of human seasonal influenza viruses (H1N1 and H3N2) expressed as virus-like particles (VLPs)

mRNA constructs

Sanofi (France) Nucleic acid-based Phase 2

Monovalent and quadrivalent mRNA vaccine constructs; two candidates differing only in the LNP containing the mRNA

Formerly: mRNA NA

Goal 
Next-generation influenza vaccine

mRNA Flu/COVID-19 combination vaccine

GSK (UK), CureVac (Germany) Nucleic acid-based Phase 2

Combination mRNA Flu/COVID-19 vaccine with flu portion targeting multiple strains of the flu virus and the COVID-19 part focusing on the spike protein of the SARS-CoV-2 virus

Goal 
Next-generation combination COVID + influenza vaccine

mRNA LNP prime and intranasal PHC boost

Georgia State University (US) Nucleic acid-based Preclinical

Heterologous sequential mRNA LNP priming followed by intranasal protein nanoparticle boosting immunization to confer optimal cross-protection against antigenically drifted and shifted influenza strains.

See also Georgia State University’s, HA/GP nanoparticles and cGAMP-adjuvanted multivalent mRNA vaccines

mRNA LNP vaccine encoding a Y2 COBRA HA immunogen

University of North Carolina (US), University of Georgia (US) Nucleic acid-based Preclinical

mRNA LNP vaccine encoding a Y2 COBRA HA immunogen, which is based on a full length HA consensus sequence; adjuvanted with acetlyated dextran microparticles (Ace-DEX MPs) encapsulating a STING agonist.

mRNA-1010

Moderna (US) Nucleic acid-based Phase 3

Modified mRNA-based lipid nanoparticle vaccine candidate mRNA-1010 (in phase 3), a quadrivalent formulation with HA antigens from four seasonal influenza strains (A/H1N1, A/H3N2, and B/Yamagata- and B/Victoria-lineages)

Goal 
Next-generation influenza vaccine

Matz 2024 (PMID: 39416092), Lee 2023 (PMID: 37336877), Bahl 2022 , Dolgin 2021 (PMID: 34635829), Feldman 2019 (PMID: 31079849), Bahl 2017 (PMID: 28457665), Liang 2017 (PMID: 28958578), Lindgren 2017 (PMID: 29181005), NCT06602024 (P3), NCT05827978 (P3), NCT05566639 / EudraCT 2022-001638-12 (P3), NCT05415462 (P3), NCT05606965 (P2), NCT05868382 (P2), NCT05397223 (P1), NCT04956575 (P1), NCT03076385 (P1), NCT03345043 (P1), Developer website, Press release 8-1-2024, Press Release 5-2-2024, Press Release 3-27-2024, Press Release 1-8-2024, Press Release 9-13-2023, Press Release 8-3-2023, Press Release 5-4-2023, Press Release 4-11-2023, Press Release 2-16-2023, Press Release 9-8-2022, Press Release 6-7-2022, Press Release 3-24-2022, Press Release 12-10-2021, Press Release 7-7-2021, Moderna Presentation Sep 2024, Moderna Presentation Jan 2024, Moderna Presentation 2022

mRNA-1011 and mRNA-1012

Moderna (US) Nucleic acid-based Phase 2

Modified mRNA lipid nanoparticles mRNA-1011/1012 which are seasonal penta-/hexa-valent vaccine candidates that includes more HA antigens (e.g. H3, H1) to expand strain matching

Goal 
Next-generation influenza vaccine

mRNA-1020 and mRNA-1030

Moderna (US) Nucleic acid-based Phase 2

Modified mRNA lipid nanoparticles mRNA-1020 and mRNA-1030 which incorporate HA and NA antigens to target more conserved regions of the virus

Goal 
Next-generation influenza vaccine

mRNA-1083

Moderna (US) Nucleic acid-based Phase 3

Combination SARS-CoV-2 (COVID-19) and influenza vaccine. Single dose mRNA vaccine encoding for the COVID-19 spike protein and flu HA glycoproteins of 4 flu strains. mRNA-1083 comprises components of mRNA-1010, Moderna's next-generation vaccine candidate for seasonal influenza, and mRNA-1283, Moderna's next-generation COVID-19 vaccine candidate.

(Formerly: mRNA-1073 and mRNA-1083)

Goal 
Next-generation combination COVID + influenza vaccine

mRNA-1230

Moderna (US) Nucleic acid-based Phase 1

Multi-component mRNA SARS-CoV-2 (COVID-19), influenza and respiratory syncytial virus (RSV) vaccine administered intramuscularly.

Goal 
Next-generation combination COVID + influenza vaccine

mRNA-Flu

National Institute for Public Health and the Environment (Netherlands) Nucleic acid-based Preclinical

Nucleoside-modified mRNA-LNP encoding three conserved internal proteins of H1N1 influenza virus, NP, M1, and PB1

mRNA-LNP

University of Pennsylvania (US), Icahn School of Medicine at Mount Sinai (US) Nucleic acid-based Preclinical

Nucleoside modified mRNA vaccine constructs encoding either conserved antigens, or hemagglutinin antigens from all 20 known influenza A and B virus subtypes aimed at inducing antigen-specific cellular and humoral immune responses to protect against diverse influenza virus strains.

mRNA/LNP vaccine

Merck & Co. (US) Nucleic acid-based Preclinical

LNP-encapsulated chemically modified mRNA vaccines encoding various forms of influenza antigens

Multi-epitope mRNA-based vaccines (MH, MH-T, and MH-TF)

Key Laboratory of Jilin Province for Zoonosis Prevention and Control (China) Nucleic acid-based Preclinical

Self-assembled mRNA-based multi-epitope influenza vaccine, which combines three conserved antigens derived from the influenza A virus (M2 ion channel’s extracellular domain (M2e), the conserved epitope of located in HA2 of hemagglutinin (H1, H3, B), and HA1 of hemagglutinin)

Multimeric-001 (M-001)

BiondVax Pharmaceuticals (Israel) Recombinant proteins Phase 3

A single recombinant protein of 9 conserved M1, NP, and HA epitopes; aimed at inducing T cell responses and enhanced B-cell responses to circulating and novel strains.

Goal
Universal or broadly protective influenza vaccine

Multiple HA-DNA

University of Oslo (Norway) Nucleic acid-based Preclinical

DNA-encoded vaccine proteins targeting APCs; uses either the ectodomain of NA as an antigen, or HA genes from 16 different HAs representing nearly all of the different HA subtypes (except H1 and H7) and inserts them into a DNA vaccine format; aimed at inducing NA immunity and delivery of the HA protein antigens to MHC class II molecules on APCs.

Multivalent DNA nanovaccine

Taizhou University (China) Non-VLP nanoparticles Preclinical

pβH7N2SH9/DGL NPs developed by encapsulating the pβH7N2SH9 within the dendrigraft poly-l-lysines nanoparticles

Multivalent Modified mRNA

GSK (UK), CureVac (Germany) Nucleic acid-based Phase 2

An mRNA-based modified, multivalent construct including the 4 WHO recommended influenza strain antigens.

Goal 
Next-generation influenza vaccine

MVA-NP

German Center of Infection Research (DZIF) (Germany) Virus-vectored Preclinical

Recombinant MVA candidate vaccines that deliver the highly conserved internal nucleoprotein (NP) of IAV under the transcriptional control of five newly designed chimeric poxviral promoters to further increase the immunogenic properties of the recombinant viruses (MVA-NP)

MVA-NP+M1 (VTP-100)

Barinthus Biotherapeutics (UK) Virus-vectored Phase 2

Modified vaccinia Ankara (MVA)–vectored construct expressing nucleoprotein (NP) and M1 protein (MVA-NP+M1); targets T cell responses to the nucleoprotein and matrix 1 core proteins of the influenza virus; co-administered with licensed quadrivalent inactivated influenza virus vaccine.

Goal
Universal or broadly protective influenza vaccine

MVA-vectored vaccines

Emergent BioSolutions (US) Virus-vectored Preclinical

MVA-vectored vaccines expressing HA, NP, M1, M2, repeats of M2e or as tandem repeats (METR), and M2e with transmembrane region and cytoplasmic loop (M2eTML) as single antigens that were delivered separately or in combination.

N1-I COBRA NA antigen

University of Georgia (US) Recombinant proteins Preclinical

COBRA (computationally optimized broadly reactive antigens) generated N1-I NA vaccine designed to cross react with avian, swine and human influenza viruses of N1 NA subtype.

N2-MPP

Icahn School of Medicine at Mount Sinai (US) Recombinant proteins Preclinical

Recombinant influenza virus N1 neuraminidase vaccine candidate, N1-MPP, adjuvanted with CpG 1018, a TLR9 agonist, designed to contribute to the development of a broadly protective NA-based influenza virus vaccine candidate. Formerly N1-MPP and rNA.

N2-VLPs

University of Natural Resources and Life Sciences Vienna (BOKU) (Austria) Virus-like particles (VLP) Preclinical

VLPs generated in insect cells, that are based on self-assembly and budding of the human immunodeficiency virus 1 (HIV-1) gag protein, and display N2 NA on their surface

NA-F2A-HA mRNA-LNP

Duke University (US) Nucleic acid-based Preclinical

An mRNA vaccine platform that delivers NA and HA as a single open reading frame (ORF) to enable expression of multiple unmodified antigens from a single mRNA, using a unique glycoprotein organization with an artificial furin cleavage site and 2A ribosome-skipping sequences.

NA-Mi3 nanoparticles

Utrecht University (Netherlands), Ghent University (Belgium) Non-VLP nanoparticles Preclinical

Soluble tetrameric NA antigens of the N1 and N2 subtypes conjugated to Mi3 self-assembling protein nanoparticles using the SpyTag-SpyCatcher system.

NA-targeting circRNA vaccine

Sun Yat-sen University (China) Nucleic acid-based Preclinical

Circular RNA (circRNA) vaccines containing N1, N2, and influenza B virus NA antigens to elicit broad-spectrum NA immunity against heterologous influenza

NA-VLPs

King Mongkut's University of Technology Thonburi (Thailand) Virus-like particles (VLP) Preclinical

Recombinant NA protein synthesized and assembled into VLPs, aimed at inducing anti-NA antibodies

NA2 VLP

Auburn University (US), Emory-UGA CEIRS (US) Virus-like particles (VLP) Preclinical

Vaccine containing the NA protein from A/Perth/16/2009 (H3N2) and the matrix 1 (M1) protein from A/MI/73/2015, formulated with a water-in-oil-in-water adjuvant

NAe-HA and M2e-HA

Georgia State University (US) Influenza virus-based Preclinical

Inactivated, replication-competent recombinant influenza virus expressing chimeric HA molecules with a conserved NA epitope (NAe) or conserved matrix protein (M2e) or chimeric 4xM2e-HA fusion proteins with 4M2e epitopes inserted into the H3 HA N-terminus; aimed at inducing antibody responses to conserved epitopes for heterosubtypic immunity.

Nano-Flu (qNIV)

Novavax (US), Emergent BioSolutions (US) Non-VLP nanoparticles Phase 3

Recombinant Spodoptera frugiperda (Sf9) insect cell or baculovirus system-derived, quadrivalent haemagglutinin nanoparticle influenza vaccine (qNIV), formulated with a saponin-based adjuvant, Matrix-M™.

Goal 
Next-generation influenza vaccine

NasoVAX

Altimmune (US) Virus-vectored Phase 2

Replication-deficient adenovirus serotype 5 construct designed to express influenza HA (H1) in nasal epithelial cells; administered as a nasal spray.

Goal
Next-generation influenza vaccine

NM2e@DDAB/PLA nanovaccine

Chinese Academy of Sciences (China) Non-VLP nanoparticles Preclinical

Fusion protein expressing the extracellular domain of matrix 2 (M2e) and nucleoprotein, NM2e, adjuvanted with a cationic solid lipid nanoadjuvant fabricated using poly(lactic acid) (PLA) and dimethyl-dioctadecyl-ammonium bromide (DDAB), to generate an NM2e@DDAB/PLA nanovaccine (Nv).

NMHC

Chinese Academy of Sciences (China) Recombinant proteins Preclinical

Recombinant protein, NMHC, consisting of viral conserved epitopes and a superantigen fragment

OVX836

Osivax (France) Non-VLP nanoparticles Phase 2

Self-assembling nanoparticle with multiple copies of full-length NP antigens; aimed at stimulating antibodies, cytotoxic T cells, and T helper cells.

Goal
Universal or broadly protective influenza vaccine

Isakova-Sivak 2023 (PMID: 37517421), Leroux-Roels 2023 (PMID: 37517422), Withanage 2022 (PMID: 34653245), Leroux-Roels 2022 (PMID: 35464450), Del Campo 2021 (PMID: 34177921), Horizon 2020, Del Campo 2019 (PMID: 30701093), NCT06582277 (P2a), NCT05569239 (P2b), NCT05734040 (P2a), NCT05284799 (P2a), NCT05060887 / EudraCT 2021-002535-39 (P2a), NCT04192500 (P2a), NCT05184387 (Observational), NCT03594890 (P1), Press Release 11-14-2024, Press Release 9-10-2024, Press Release 3-26-2024, Press Release 12-5-2023, Press Release 7-28-2023, Press Release 6-15-2023, Press Release 3-28-2023, Press Release 12-21-2022, Press Release 9-1-2022, Press Release 6-23-2022, Press Release 5-25-2022, Press Release 5-17-2022, Press Release 4-21-2022, Press release 12-2-2021, Press release 9-10-2020, Press release 7-8-2020, Press release 4-9-2020, Press Release 1-21-2020, Press release 12-5-2019, Development update 12-5-2019, Developer website, European Commission Funding

P22-HAhead VLP

Indiana University (US) Virus-like particles (VLP) Preclinical

Using SpyTag/SpyCatcher covalent attachment strategy, conjugates bacteriophage P22 VLPs with multiple copies of the HA head domain in a high-density display of multivalent antigens; aimed at conferring a potent antibody response in a rapid, scalable production system (e.g., for use in outbreak situations).

pABOL-formulated saRNA vaccine

Imperial College London (UK) Nucleic acid-based Preclinical

Bioreducible cationic polymer, pABOL used for the delivery of a self-amplifying RNA (saRNA) vaccine expressing either haemagglutinin (HA) from H1N1 or H3N2 influenza virus in a prime boost regime

PapMV-sM2e nanoparticles

Laval University (Canada) Non-VLP nanoparticles Preclinical

 

Two types of PapMV (papaya mosaic virus) nanoparticles harboring the M2e and NP antigens; aimed at inducing broadly protective immune responses.

pEx 4M2e

Slovak Academy of Science (Slovak Republic) Nucleic acid-based Preclinical

DNA vaccine aimed at inducing an anti-M2e immune response by inserting the sequence for truncated NS1 protein followed by 4xM2e into the expression vector pEx (PTriEx-4).

PLGA nanoparticles

Sunway University (Malaysia) Non-VLP nanoparticles Preclinical

Self-adjuvanting PLGA nanoparticles encapsulating six conserved peptides

Polyvalent DNA vaccine

Statens Serum Institut (Denmark) Nucleic acid-based Preclinical

Needle-free intradermal application of a broadly protective polyvalent influenza A DNA vaccine encoding HA and NA proteins derived from less glycosylated pandemic H1N1 (2009) and H3N2 (1968) virus strains and nucleoprotein (NP) and matrix proteins (M1 and M2) from a different pandemic H1N1 (1918) strain.

PR8HA-VLP

University of Wisconsin (US), Georgia Institute of Technology (US) Virus-like particles (VLP) Preclinical

VLP-based vaccine presenting multiple copies of the HA from A/Puerto Rico/8/1934 (PR8HA-VLP)

Prime and HA

Yale University (US) Recombinant proteins Preclinical

Intranasal recombinant HA protein booster; used following intramuscular HA-encoding mRNA-LNP prime vaccine to elicit protective mucosal immune responses and confer sterilizing immunity against influenza virus infection.

PROTAC

Chinese Academy of Sciences (China) Influenza virus-based Preclinical

Proteolysis-targeting chimeric (PROTAC) vaccine technology that uses the host cellular ubiquitin-proteasome system to conditionally degrade influenza viral proteins that aims to elicit robust and broad humoral, mucosal and cellular immune responses against homologous and heterologous viral challenges

Quadrivalent HA mRNA

Greenlight Biosciences (US) Nucleic acid-based Preclinical

Quadrivalent mRNA vaccine encoding HA from four seasonal influenza viruses

Quadrivalent VLP (QVLP)

Medicago (Canada) Virus-like particles (VLP) Phase 3

Nicotiana benthamiana plant-derived (Proficia®) HA-bearing quadrivalent virus-like particle (QVLP); aimed at stimulating antibody and cellular immune responses.

Goal
Next-generation influenza vaccine

Quadrivalent VLPs

National Health Research Institutes (Taiwan) Virus-like particles (VLP) Preclinical

An insect cell-based baculovirus expression system used to generate rBVs bearing influenza HA, NA, and M1 genes from four seasonal influenza vaccine strains which are used to produce insect cell-based VLPs as quadrivalent seasonal influenza vaccine candidates

rAAV-COBRA

St Jude Children’s Research Hospital (US) Virus-vectored Preclinical

Recombinant adenovirus-associated virus (rAAV) vector expressing a computationally optimized broadly reactive antigen (COBRA)-derived influenza H1 hemagglutinin (HA) with modestly enriched CpG motifs to evoke a robust and long-lasting immune response

rAd-HA2

Health Canada (Canada), University of Ottawa (Canada) Virus-vectored Preclinical

Recombinant adenovirus vaccine (rAd) carrying a synthetic HA2 representing the consensus sequence of all influenza B virus HAs

rAd-NP-M2e-GFP

Jilin University (China) Virus-vectored Preclinical

Packaged recombinant adenovirus rAd-NP-M2e-GFP expressing multiple copies of influenza virus conserved antigens NP and M2e and packaged empty vector adenovirus rAd-GFP

rAd/NP + rAd/HA-M2e

Ewha Womans University (Korea) Virus-vectored Preclinical

Recombinant adenovirus-based vaccine that expresses influenza NP, HA, and M2e in a mixture of rAd/NP and rAd/HA-M2e administered intranasally or intramuscularly.

RAM-IGIP

University of Georgia (US) Influenza virus-based Preclinical

Attenuated MLV (modified live virus) vaccine, built by rearranging FLUAV genome segments and incorporating the IgA-inducing protein

Reassortant LAIV with modified NS-1 and NP

Institute of Experimental Medicine (Russia) Influenza virus-based Preclinical

Reassortant LAIV expressing modified NP and NS1 genes aimed at inducing a robust T-cell response

rM2e-ΔPly

Chongqing Medical University (China) Recombinant proteins Preclinical

A novel rM2e-ΔPly protein containing multiple M2e originated from different species of IAV expressed in Escherichia coli (E. coli)

rMVA-k1-k2

Federal Medical-Biological Agency (Russia) Virus-vectored Preclinical

Epitope-based vaccine against influenza based on modified vaccinia Ankara (MVA) vector and using an algorithm to select epitopes from conserved fragments of the NP, M1 and HA proteins of influenza A and B

rNA antigens

Ghent University (Belgium), Sanofi (France) Recombinant proteins Preclinical

Computationally engineered consensus NA sequences forming 3 recombinant NA proteins.

rNP plus BPPcysMPEG

Helmholtz Centre for Infection Research (Germany), Instituto de Medicina y Biología Experimental de Cuyo (IMBECU) (Argentina) Recombinant proteins Preclinical

Recombinant protein based vaccine containing the NP antigen adjuvanted with a TLR2/6 agonist, the BPPcysMPEG adjuvant

rNP+SLA-SE

Trudeau Institute (US) Recombinant proteins Preclinical

Adjuvanted recombinant nucleoprotein construct; aimed at generating cellular and humoral immunity to conserved influenza A proteins.

RSM2eFP spore vaccine

Beijing Institute of Microbiology and Epidemiology (China) Influenza virus-based Preclinical

Recombinant influenza vaccine using Bacillus subtilis spores expressing M2e-FP protein (RSM2eFP) administered via aerosolized intratracheal inoculation (i.t.).

rTET-NA

Sanofi (France) Recombinant proteins Preclinical

Soluble recombinant NAs produced from a number of subtypes by fusion of the globular head domain with the tetrabrachion tetramerization domain (rTET-NA), added to a quadrivalent HA-based influenza vaccine

rVSV-EΔM-tM2e

University of Manitoba (Canada) Virus-vectored Preclinical

rVSV-based vaccine candidates expressing the ectodomain of influenza matrix protein (M2e) and/or conserved hemagglutinin stalk regions (HA stalk) fused with the DC-targeting domain of EboGP (E1M) to generate E1M-tM2e or E1M-HM2e, which is UV-inactivated. 

S-FLU

University of Oxford (UK), University of Melbourne (Australia) Influenza virus-based Preclinical

Non-replicating form of pseudotyped influenza virus, inactivated by suppression of the HA signal sequence (S-FLU); aimed at inducing heterotypic protection through activation of cross-reactive T cells in the lung.

sa-mRNA (SQ012)

CSL Seqirus (Australia) Nucleic acid-based Phase 1

Self-amplifying mRNA bicistronic influenza vaccine candidate developed to co-express HA and NA

Formerly: sa-mRNA bicistronic vaccine 

Goal
Next-generation influenza vaccine

sa-RNA (ARCT-2138)

Arcturus Therapeutics (US), CSL Seqirus (Australia) Nucleic acid-based Phase 1

Self-amplifying RNA seasonal influenza vaccine (ARCT-2138) administered intramuscularly

Goal
Next-generation influenza vaccine

saRNA

Pfizer (US) Nucleic acid-based Phase 2

Self-amplifying ribonucleic acid (saRNA) vaccine delivered intramuscularly

Goal 
Next-generation influenza vaccine

Sbmut HA

Duke University (US) Recombinant proteins Preclinical

An HA antigenic mixture–based vaccine with four positions of the Sb antigenic site randomized within the back-bone of an H1 HA

Scrambled HA (scrHA)

University of Wisconsin (US) Recombinant proteins Preclinical

An H3 HA vaccine antigen with various amino acids at immunodominant epitopes of the HA head domain.

Self amplifying mRNA

University of Minnesota (US) Nucleic acid-based Preclinical

Self-amplifying mRNA vaccine encoding the influenza A virus nucleoprotein that is encapsulated in modified dendron-based nanoparticles.

Self assembling peptides displaying M2e and HA2

Russian Academy of Sciences (Russia) Non-VLP nanoparticles Preclinical

Self-assembling nanoparticles displaying M2e and HA stalk epitopes aimed at inducing humoral and T-cell responses

Self-assembled multiepitope nanoparticles (MHF)

Jilin University (China) Non-VLP nanoparticles Preclinical

Multiepitope nanovaccine, MHF, made up of conserved linear epitopes of HA2, M2e, and NP fused to either three surface loops on the P domain, or to ferritin. (Formerly: HMN-PP)

Self-assembled protein nanocages (SAPNs)

Georgia Institute of Technology (US) Non-VLP nanoparticles Preclinical

A broadly cross-reactive influenza vaccine developed by functionalizing self-assembled protein nanocages (SAPNs) with multiple copies of the hemagglutinin stalk on the outer surface and matrix protein 2 ectodomain on the inner surface

Self-assembling protein nanoparticles (SApNPs)

Scripps Research Institute (US) Non-VLP nanoparticles Preclinical

Single-component self-assembling protein nanoparticles (SApNPs) presenting the conserved extracellular domain of matrix protein 2 (M2e)

Single ADCC activating peptides

University of Hong Kong (Hong Kong SAR, China) Recombinant proteins Preclinical

Novel constructs based on ADCC-inducing peptide in the HA1 and HA2 regions.

SpyTagged noro-VLP

Tampere University (Finland) Virus-like particles (VLP) Preclinical

Uses a modular vaccine platform based on the noro-VLP, fused with highly conserved antigens, the ectodomain of M2e protein and a minimized stem-fragment of HA.

Stabilized headless HA stem nanoparticles

NIAID (US) Non-VLP nanoparticles Phase 1

Stabilized headless HA stem trimers on self-assembling nanoparticles; aimed at stimulating broadly protective immunity against novel viruses.

Goal
Universal or broadly protective influenza vaccine

Synthetic multicomponent nanovaccine

University of Quebec at Montreal (Canada) Non-VLP nanoparticles Preclinical

Multicomponent nanofilaments, composed of cross-β-sheet nanofilaments exposing the M2e epitope from the influenza virus and the TLR7 agonist IMQ, aimed at inducing a protective M2e-specific immune response.

T4-M2e VLP

Huazhong Agricultural University (China) Virus-like particles (VLP) Preclinical

T4 VLP construct displaying three tandem copies of M2e from human, swine and avian influenza; aimed at inducing both humoral and cellular immune responses.

ta-RNA, sa-RNA

BioNTech (Germany), Johannes Gutenberg University Mainz (Germany) Nucleic acid-based Preclinical

RNA vaccine approach based on a novel split-vector system using trans-amplifying RNA (taRNA) or self-amplifying (saRNA) encoding HA antigen.

TAT-NP

Shanghai Institute of Biological Products (China) Recombinant proteins Preclinical

Recombinant protein construct, based on the conserved protein NP and protein transduction domain TAT; aimed at inducing cross-protective cellular and humoral immune responses.

Trimeric HA-Fc

University of Maryland (US) Recombinant proteins Preclinical

Monomeric IgG Fc fused to influenza virus hemagglutinin (HA) Ag with a trimerization domain

TX98-129

University of South Dakota (US), University of Illinois Urbana-Champaign (US) Influenza virus-based Preclinical

Recombinant influenza virus based vaccine that expresses a chimeric HA (HA-129) derived from HAs of four genetically distinct swine influenza A viruses (H1N1) that had a history of zoonotic transmission. The chimeric HA was obtained through molecular breeding (gene shuffling) technology from the four original parental HAs. Designed to induce broadly protective immunity against genetically divergent HAs.

VRC H1ssF_3928 mRNA-LNP

NIAID (US) Nucleic acid-based Phase 1

mRNA expressing influenza H1 stabilized stem (H1ss) covalently fused to H. pylori ferritin (F)

Goal
Universal or broadly protective influenza vaccine

VT-105

Versatope Therapeutics (US) Non-VLP nanoparticles Preclinical

Combines diverse variants of influenza strains displayed on a single nano-sized rOMV (recombinant outer membrane vesicle); VT-105 is based on the M2 protein; targets the virus-infected cell to engage cell-mediated immune responses against all influenza strains.

VXA-A1.1 oral tablet

Vaxart (US) Virus-vectored Phase 2

Replication-defective adenovirus type-5 vectored construct that expresses HA; includes a novel toll-like receptor 3 (TLR3 ligand) agonist as an adjuvant; administered orally in tablets designed to release the virus in the ileum, with the potential to stimulate cellular and mucosal immunity and serum antibody.

Goal 
Next-generation influenza vaccine

Wyeth/IL-15/5flu

University of Hong Kong (Hong Kong SAR, China) Virus-vectored Preclinical

 

Live, replication competent vaccinia Wyeth Backbone carrying 5 full-length influenza proteins derived from H5N1 viruses (NP, HA NA, M1, and M2) and IL-15 as a molecular adjuvant; aimed at eliciting robust CD4+ and CD8+ T cell responses.

α-1,3-GT

University of Hong Kong (Hong Kong SAR, China) Influenza virus-based Preclinical

LAIV expressing galactose-α-1,3-galactose (α-Gal) epitopes; aimed at enhancing antigen update, resulting in phagocytosis, NK cell-mediated cell killing and ADCC responses and cross-reactive protection against group 1 and group 2 influenza viruses; administered intranasally.

ΔNS1 virus

Icahn School of Medicine at Mount Sinai (US) Influenza virus-based Preclinical

Live attenuated Influenza A virus lacking the NS1 gene (ΔNS1) expressing cHAs corresponding to the head of H8 and the stalk of H1 (cH8/1) and to the head of H11 and the stalk of H1 (cH11/1); administered intranasally aimed at inducing an innate antiviral response

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