» Articles » PMID: 33440898

Chimeric Hemagglutinin-Based Live-Attenuated Vaccines Confer Durable Protective Immunity Against Influenza A Viruses in a Preclinical Ferret Model

Abstract

Epidemic or pandemic influenza can annually cause significant morbidity and mortality in humans. We developed novel chimeric hemagglutinin (cHA)-based universal influenza virus vaccines, which contain a conserved HA stalk domain from a 2009 pandemic H1N1 (pH1N1) strain combined with globular head domains from avian influenza A viruses. Our previous reports demonstrated that prime-boost sequential immunizations induced robust antibody responses directed toward the conserved HA stalk domain in ferrets. Herein, we further followed vaccinated animals for one year to compare the efficacy and durability of these vaccines in the preclinical ferret model of influenza. Although all cHA-based immunization regimens induced durable HA stalk-specific and heterosubtypic antibody responses in ferrets, sequential immunization with live-attenuated influenza virus vaccines (LAIV-LAIV) conferred the best protection against upper respiratory tract infection by a pH1N1 influenza A virus. The findings from this study suggest that our sequential immunization strategy for a cHA-based universal influenza virus vaccine provides durable protective humoral and cellular immunity against influenza virus infection.

Citing Articles

Sequential immunization with chimeric hemagglutinin ΔNS1 attenuated influenza vaccines induces broad humoral and cellular immunity.

Rathnasinghe R, Chang L, Pearl R, Jangra S, Aspelund A, Hoag A NPJ Vaccines. 2024; 9(1):169.

PMID: 39300090 PMC: 11413010. DOI: 10.1038/s41541-024-00952-7.


Disulfide-stabilized trimeric hemagglutinin ectodomains provide enhanced heterologous influenza protection.

Liu D, Zhong X, Ru Y, Zhao S, Liu C, Tang Y Emerg Microbes Infect. 2024; 13(1):2389095.

PMID: 39101691 PMC: 11334750. DOI: 10.1080/22221751.2024.2389095.


Protective efficacy of a universal influenza mRNA vaccine against the challenge of H1 and H5 influenza A viruses in mice.

Li Y, Wang X, Zeng X, Ren W, Liao P, Zhu B mLife. 2024; 2(3):308-316.

PMID: 38817814 PMC: 10989953. DOI: 10.1002/mlf2.12085.


Immunogenicity of chimeric hemagglutinins delivered by an orf virus vector platform against swine influenza virus.

do Nascimento G, de Oliveira P, Butt S, Diel D Front Immunol. 2024; 15:1322879.

PMID: 38482020 PMC: 10933025. DOI: 10.3389/fimmu.2024.1322879.


Chimeric hemagglutinin split vaccines elicit broadly cross-reactive antibodies and protection against group 2 influenza viruses in mice.

Puente-Massaguer E, Vasilev K, Beyer A, Loganathan M, Francis B, Scherm M Sci Adv. 2023; 9(37):eadi4753.

PMID: 37703367 PMC: 10499326. DOI: 10.1126/sciadv.adi4753.


References
1.
Nachbagauer R, Feser J, Naficy A, Bernstein D, Guptill J, Walter E . A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial. Nat Med. 2020; 27(1):106-114. DOI: 10.1038/s41591-020-1118-7. View

2.
Isakova-Sivak I, Matyushenko V, Kotomina T, Kiseleva I, Krutikova E, Donina S . Sequential Immunization with Universal Live Attenuated Influenza Vaccine Candidates Protects Ferrets against a High-Dose Heterologous Virus Challenge. Vaccines (Basel). 2019; 7(3). PMC: 6789596. DOI: 10.3390/vaccines7030061. View

3.
Iuliano A, Roguski K, Chang H, Muscatello D, Palekar R, Tempia S . Estimates of global seasonal influenza-associated respiratory mortality: a modelling study. Lancet. 2017; 391(10127):1285-1300. PMC: 5935243. DOI: 10.1016/S0140-6736(17)33293-2. View

4.
Krammer F, Pica N, Hai R, Margine I, Palese P . Chimeric hemagglutinin influenza virus vaccine constructs elicit broadly protective stalk-specific antibodies. J Virol. 2013; 87(12):6542-50. PMC: 3676110. DOI: 10.1128/JVI.00641-13. View

5.
Nachbagauer R, Kinzler D, Choi A, Hirsh A, Beaulieu E, Lecrenier N . A chimeric haemagglutinin-based influenza split virion vaccine adjuvanted with AS03 induces protective stalk-reactive antibodies in mice. NPJ Vaccines. 2017; 1. PMC: 5707880. DOI: 10.1038/npjvaccines.2016.15. View