Influenza M2 virus-like particle vaccination enhances protection in combination with avian influenza HA VLPs

Abstract

Despite the ability to induce a broad range of cross protection, M2e5x virus-like particles (VLPs) alone provide limited vaccine efficacy and confer low efficacy of protection against highly pathogenic avian influenza virus (HPAIV) infection in chickens. Avian influenza hemagglutinin (HA) has been a major antigenic target that enhances humoral immunity, but the efficacy of avian HA-based vaccines against HPAIV needs to be further improved. In this study, we evaluated the vaccine efficacy induced by combination of conserved tandem repeat M2e5x VLPs and HA VLPs against an avian influenza virus. We found that combinatorial vaccine elicited higher levels of reassortant H5N1 (rgH5N1) virus-specific IgG, IgG1, IgG2a and IgA antibody responses compared to M2e5x VLPs in sera and lungs of mice. Combinatorial VLPs vaccination induced higher levels of CD8 + T cell and germinal center B cell responses in lung and spleen compared to M2e5x VLPs. Combinatorial VLPs vaccination showed significantly reduced inflammatory responses and lung viral loads upon rgH5N1 virus challenge infection, resulting in less body weight loss compared to M2e5x VLPs alone. These results indicate that immune responses to both M2e and HA might provide a strategy of vaccination inducing enhanced protection against avian influenza virus.

Broadly Protective Strategies Against Influenza Viruses: Universal Vaccines and Therapeutics

“…The development and discovery of broadly neutralizing antibodies also illustrate the important contributions these therapeutics can offer in preventing and improving disease outcomes associated with influenza virus infection. Additionally, these studies have provided an insight into novel combinatorial approaches, as seen with studies combining M2e5x VLPs and HA-VLPs to improve vaccine immunogenicity or by combining broadly neutralizing antibodies with current antivirals to improve recovery from influenza virus infection (Nakamura et al, 2013;Tharakaraman et al, 2015;Kang et al, 2019). While the ultimate goal of developing a truly universal influenza virus vaccine has yet to be achieved, the progress made in pursuit of this goal shows the exciting promise of these new approaches for improving influenza disease outcomes and as well as the public health burden associated with inefficient protection against influenza virus infection.…”

“…These M2e-based vaccines elicited M2 specific antibody responses and protected mice against influenza A virus challenge, highlighting the importance of M2e mediated protection and the importance of considering the M2e protein when formulating universal influenza vaccines (Ionescu et al, 2006;Bessa et al, 2008;Denis et al, 2008). Another approach to improve M2e antibody responses involved expressing a membrane anchored tandem repeat of M2e epitope sequences of human, swine, and avian origin on recombinant baculovirus VLPs (M2e5x VLP) (Kim et al, 2013;Kang et al, 2019). The M2e5x VLPs induced M2e-specific antibody responses against H1N1, H3N2, and H5N1 and conferred protection in mice against both H1N1 and H3N2 challenges (Kim et al, 2013).…”

“…The M2e5x VLPs induced M2e-specific antibody responses against H1N1, H3N2, and H5N1 and conferred protection in mice against both H1N1 and H3N2 challenges (Kim et al, 2013). Recently, combinatorial vaccination with both M2e5x VLPs and HA-VLPs generated higher antibody titers, reduced lung inflammation, and provided improved protection against lethal challenge with H5N1 as compared to M2e5x VLP alone (Kang et al, 2019). While this study did not address whether these responses were greater than with HA-VLP vaccination alone, this study demonstrated the utility of combinatorial vaccination approaches to induce broader protection.…”

Influenza vaccine efficacy induced by orally administered recombinant baculoviruses

“…At day 4 post-challenge, half of the mice from each group were randomly selected and sacrificed for sample collection. Trachea, lung, intestine, spleen, bone marrow, vaginal secretions, and feces were collected and processed individually for further analysis of several immunological parameters as described before [1,[19][20][21][22].…”

“…Lung viral titer was determined using the method previously described [20]. Briefly, lung tissues were individually homogenized in 1ml PBS and passed through a cell strainer to remove tissue debris.…”