Vaccine Efficacy Induced by 2009 Pandemic H1N1 Virus-Like Particles Differs from that Induced by Split Influenza Virus

ABSTRACT

Influenza virus-like particles (VLPs) vaccines are highly immunogenic, showing strong protective efficacy against homologous virus infection compared to split vaccine. However, a comparative efficacy study against heterosubtypic virus infection between VLPs and split vaccine has yet to been reported. In this study, we generated VLPs vaccine containing hemagglutinin (HA) and matrix protein (M1) of the 2009 pandemic H1N1, and investigated the protective efficacies induced by VLPs vaccine and commercial monovalent H1N1 pandemic split vaccine from Sanofi-Pasteur. Mice were intramuscularly immunized with either VLPs vaccine or split vaccine and subsequently challenge-infected with homologous virus (A/California/04/2009, H1N1) or heterosubtypic virus (A/Philippines/82, H3N2) after 4.5 months. VLPs vaccination demonstrated a higher level of protective efficacy against homologous viruses compared to split vaccine, as lessened lung viral loads and minuscule levels of proinflammatory lung cytokines IFN-gamma and IL-6 were observed. Protective efficacies were close to non-existent in VLP-immunized mice challenged with heterosubtypic viruses (H3N2). In contrast, split vaccine showed lower vaccine efficacy against homologous virus than VLP vaccine, but conferred better protection against heterosubtypic viruses through lung viral loads reduction and heightened survival rate. These results indicate that influenza VLPs provide better protective efficacy against homologous virus challenge infection, whereas split vaccine shows better protective efficacy against heterosubtypic virus challenge. Findings from the current study contribute to the rational design of vaccines conferring a broad range of protection.

KEYWORDS:

• Influenza vaccine
• virus-like particles
• split vaccine
• protection

Acknowledgments

This work was supported by grants from the National Research Foundation of Korea (NRF) (2018R1A2B6003535, 2018R1A6A1A03025124) and the Cooperative Research Program for Agriculture Science & Technology Development, Rural Development Administration, Republic of Korea (PJ01320501). We thank the animal research facility of Emory University for the approved IACUC.

Author contributions

Conceptualization, F.-S. Q.; methodology, G.-J. L., K.-B. C., formal analysis, G.-J. L., K.-B. C., K.-S. I., E.-K. M., F.-S. Q.; writing—original draft preparation, G.-J. L., K.-B. C., K.-S. I., E.-K. M., F.-S. Q., supervision, F.-S.Q.; review and editing, K.-B.C. and F.-S.Q.

Disclosure statement

The authors have no conflict of interest to declare.

Additional information

Funding

This work was supported by the the National Research Foundation of Korea [2018R1A6A1A03025124,NRF/2018R1A2B6003535]; the Cooperative Research Program for Agriculture Science & Technology Development, Rural Development Administration, Republic of Korea [PJ01320501].