Universal Influenza Vaccine Technology Landscape

The Landscape is a database of novel vaccine candidates designed to provide broader and more durable protection against circulating and pandemic influenza viruses, compared with current strain-specific seasonal influenza vaccines. CIDRAP is developing the landscape with support from the Global Funders Consortium for Universal Influenza Vaccine Development.

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Database last updated on Apr 24, 2024

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Vaccine Candidates 202 Vaccine Candidates
Vaccine in clinical trials 39 Vaccines in Clinical Trials
COVID+Flu Vaccine Candidates 4 COVID+Flu Vaccine Candidates
Developers 155 Developers
Platforms 6 Platforms
Preclinical 163
Phase 1 16
Phase 2 15
Phase 3 8
Approved 0

Database

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Preclinical
Phase 1
Phase 2
Phase 3
Approved
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Influenza virus-based

14
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Preclinical
2
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Nucleic acid-based

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Preclinical
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Non-VLP nanoparticles

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Preclinical
4
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Phase 1
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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

National Institute of Allergy and Infectious Diseases (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

Bifluagen

KJ Biosciences (US), Texas A&M University (US) Non-VLP nanoparticles Preclinical

Novel dual-domain nanoparticle fusion protein presenting two conserved antigens, M2e and HA2, on a nanoparticle protein; aimed at inducing cross protective immune responses.

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

National Institute of Allergy and Infectious Diseases (NIAID) (US) Influenza virus-based Phase 1

BPL-137 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

BWV-101

Blue Water Biotech (US), University of Oxford (UK), Instituto Butantan (Brazil) Virus-vectored Preclinical

Chimeric HA constructs displaying a highly immunogenic epitope of limited variability in the H1 HA head domain.

Cap-M2e VLPs

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

Uses Cap (capsid protein of PCV2) VLPs to display M2e antigens; aimed at providing cross-protection against diverse subtypes of influenza A virus strains.

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

ChAdOx1 NP+M1 prime, MVA-NP+M1 boost

Icahn School of Medicine at Mount Sinai (US), Jenner Institute, University of Oxford (UK) Virus-vectored Preclinical

Influenza proteins cHA, NP, and M1 delivered by ChAdOx1 and MVA viral-vectored vaccines aimed at inducing potent T and B cell responses to confer broad protection.

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

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, NCT03275389, NCT03300050, NCT02415842, 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 HA protein

University of Rochester Medical Center (US) Recombinant proteins Preclinical

Novel chimeric HA protein (cH7/3) comprised of the stem domain from seasonal H3 HA and the head domain from avian H7.

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

CLP-HAstem

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

HAstem trimer displayed on the surface of rigid capsid-like particles (CLP), using the Tag/Catcher AP205 platform.

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 designed to cross react with several IAV strains.

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; 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.

Conserved T cell epitope DNA vaccine

Saint Louis University (US) Nucleic acid-based Preclinical

T-cell targeted DNA vaccine containing multiple pan-DR- and HLA-A2 restricted, highly conserved influenza epitopes.

Status: Active

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.

dbDNA-encoded NA

Imperial College London (England) 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

National Institute of Allergy and Infectious Diseases (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); 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).

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

National Institute of Allergy and Infectious Diseases (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 (Altimmune) (UK) 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.

Glycolipid peptide

Monash University (Australia), Victoria University of Wellington (New Zealand) Recombinant proteins Preclinical

Synthetic long peptides (SLP) from immunogenic MHC class I-binding CD8+ T cell epitopes covalently attached to an α-galactosylceramide adjuvant, a natural killer T cell agonist; aimed at stimulating influenza-specific memory cytotoxic T lymphocytes and cross-protective immune responses against conserved IAV epitopes.

H1 and H3 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)

H1 mosaic HA

University of Nebraska−Lincoln (US), St Jude Children’s Research Hospital (US) Virus-vectored Preclinical

Replication-defective Adenovirus type 5-vectored mosaic HA based on full-length H1 HA or multivalent HA consensus genes; aimed at inducing cellular and humoral immune responses against divergent influenza strains.

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.

HA mini-stems

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

H5-based HA mini-stem protein folding as a trimer in a pre-fusion confirmation of the HA stem; uses a quarter of full length HA to focus the immune response to the conserved epitope of known broadly neutralizing antibodies in the stem domain of HA.

HA stem protein

National Institute of Allergy and Infectious Diseases (NIAID) (US), Indian Institute of Science (India) Recombinant proteins Preclinical

Novel approaches for constructing HA stem-fragment immunogens; aimed at overcoming HA head immunodominance and stimulating anti-stem germinal center B cell and antibody responses.

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-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-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

HA/M1 VLP

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

Sequential administration with heterosubtypic HA VLPs harboring H1, H8, and H13 from the HA phylogenetic group 1, or H3, H4, and H10 from the HA phylogenetic group 2, or in various combinations; aimed at eliciting broad protection against divergent viruses in the same HA phylogenetic group or both groups.

HA2 HA-ferritin nanoparticle

National Institute of Allergy and Infectious Diseases (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.

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.

HBc-4M2eh (Uniflu)

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

Vaccine containing 4 copies of M2e fused within the immunodominant loop of the hepatitis B virus core antigen (HBc); aimed at inducing M2e-antibody responses.

(Formerly: M2e VLP)

Goal
Universal or broadly protective influenza vaccine

Helix-A stem nanoparticle

National Institute of Allergy and Infectious Diseases (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 

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

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.

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 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 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-based VLPs (ACAM-FluA)

Ghent University (Belgium), Sanofi Pasteur (US) Virus-like particles (VLP) Phase 1

M2e-based VLP constructs; aimed at inducing cross-reactive CD8+ T cell responses.

Goal
Universal or broadly protective influenza vaccine

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

M2e5x VLP (multiple approaches)

Georgia State University (US), Kyung Hee University (S Korea) Virus-like particles (VLP) Preclinical

Conserved tandem repeat M2e5x VLPs alone or in combination with other technologies, including: HA VLPs, flagellin VLPs, IIV by microneedle patch, and intranasal administration; aimed at inducing heterosubtypic cross protective immunity.

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

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

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

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 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 Pasteur (US) 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-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

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.

(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.

Status: Active

mRNA/LNP vaccine

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

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

Multi-antigen DNA vaccine

University of Washington (US) Nucleic acid-based Preclinical

Adjuvanted multi-antigen DNA vaccine consisting of HA, M2, and NP antigens, administered in 3 sequential doses; aimed at inducing mucosal responses and cross-reactive T cell responses.

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

CureVac (Germany), GSK (US) 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)

Vaccitech (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 VLP

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

VLP containing NA from 2009 pH1N1; aimed at inducing cross-reactive NA inhibition activity as a component of a broadly protective vaccine.

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.

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

nM2Pr

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

Linear peptide constructs based on the N-terminal sequence of M2e (nM2e) and a helper T-cell epitope.

NMHC

Chinese Academy of Sciences (China) Recombinant proteins Preclinical

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

NP mRNA

Ghent University (Belgium) Nucleic acid-based Preclinical

mRNA construct encoding NP; administered intranodally; aimed at inducing systemic T cell responses and protecting against heterologous infection.

NvC-M2ex3

Universiti Putra Malaysia (Malaysia) Virus-like particles (VLP) Preclinical

M2e antigen displayed on a chimeric protein (NvC-M2ex3) VLPs.

Optimized M2e DNA vaccines

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

Uses N-terminal extracellular region of the influenza virus M2 protein (M2e) as the target antigen; constructed two optimized M2e DNA vaccines (p-tPA-p3M2e and p-p3M2e) with increased antigenic epitope density and enhanced antigen secretion.

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), NCT04192500, NCT03594890, NCT05284799, NCT05060887 / EudraCT 2021-002535-39, NCT05569239, NCT05184387, NCT05734040, 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 (England) 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

PAPB1M1 and NPPB2M2 composite immunogens in a DNA prime/viral vector boost strategy

Shanghai Public Health Clinical Center (China) Nucleic acid-based Preclinical

Two novel composite immunogens containing highly conserved T-cell epitopes of 6 influenza A virus internal antigens (based on consensus amino acid sequences of M1, M2, NP, PA, PB1, and PB2 from approximately 40,000 influenza A virus strains) cloned into 3 sequential constructs; DNA prime vaccine followed by consecutive boosting with intranasal AdC68 viral vector and intramuscular Tiantan vaccinia (TTV) virus vector.

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).

pH-responsive NP vaccine

Vanderbilt University (US) Non-VLP nanoparticles Preclinical

pH-responsive polymeric nanoparticle vaccine for generating antigen-specific CD8+ TRM cells in the lungs; administered intranasally; aimed at eliciting rapid generation of protective CD8+ TRM cells in the lungs.

PIV5-NA

University of Georgia (US) Virus-vectored Preclinical

Parainfluenza virus 5 recombinant vaccine candidate expressing NA (PIV5-NA) from a pandemic influenza (pdmH1N1) virus or highly pathogenic avian influenza (H5N1) virus; aimed at eliciting robust, cross-reactive protection.

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.

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

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-SHA2

National Institutes for Food and Drug Control (China), Health Canada (Canada) Virus-vectored Preclinical

Recombinant adenovirus (rAd) construct encoding secreted fusion protein (codon-optimized HA2 subunit of influenza A virus fused to a trimerized form of murine CD40L).

rAd/B-NP

Ewha Womans University (Korea) Virus-vectored Preclinical

Recombinant adenovirus encoding NP of influenza B virus (rAd/B-NP); aimed at inducing B-NP-specific humoral and cellular immune responses.

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

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.

rNA antigens

Ghent University (Belgium), Sanofi Pasteur (US) 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.).

RVJ-4M2eNP

China CDC (China) Virus-vectored Preclinical

Recombinant vaccinia viruses (Tiantan strain) expressing a fusion antigen of NP and 1 or 4 copies of M2e.

rVSV-EΔM-tM2e and rVSV-EΔM-HM2e

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

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 (US) 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 (US) Nucleic acid-based Phase 1

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

Goal
Next-generation influenza vaccine

SAM-GM-CSF + SAM-NP

GSK (US) Nucleic acid-based Preclinical

Self-amplifying mRNA (SAM) vaccines expressing NP; co-administration of SAM-granulocyte-macrophage colony-stimulating factor (GM-CSF); aimed at inducing NP-specific CD8+ T cells.

saRNA

Pfizer (US) Nucleic acid-based Phase 2

Self-amplifying ribonucleic acid (saRNA) vaccine delivered intramuscularly

Goal 
Next-generation influenza vaccine

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

National Institute of Allergy and Infectious Diseases (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.

Tandiflu1 VLP

iQur (UK) Virus-like particles (VLP) Preclinical

VLP construct based on multiple conserved antigens presented on HepB tandem core platform; HepB core protein + HA stem (H1 and H3) + 3xM2e (from 3 strains) expressed in yeast; 4 conserved IAV antigens contained within a single VLP; aimed at stimulation of cross-reactive and protective polyclonal antibodies.

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.

VLP cocktail

National Institute of Allergy and Infectious Diseases (NIAID) (US) Virus-like particles (VLP) Preclinical

Mixture of VLPs individually displaying H1, H3, H5, and H7 HAs representing group 1 and group 2 viruses; aimed at protecting against circulating and novel influenza A viruses.

VLP-based vaccine

TechnoVax (US) Virus-like particles (VLP) Preclinical

VLP structures displaying alternative conformations of remodeled HAs displaying conserved subdominant antigenic sites; aimed at promoting an antibody response to neutralize a broad spectrum of influenza viruses.

VLPs

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.

VRC H1ssF_3928 mRNA-LNP

National Institute of Allergy and Infectious Diseases (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.

α-DEC-205: M2e conjugate

Universidad Autónoma del Estado de Morelos (Mexico) Recombinant proteins Preclinical

M2e peptide chemically cross-linked to a mAb specific for DEC-205, a C-type lectin present on dendritic cells, to induce heterosubtypic protection.

ΔNS1 virus

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

Live attenuated Influenza A virus lacking the NS1 gene administered intranasally aimed at inducing an innate antiviral response

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