Efficacy of Heterologous Prime-Boost Vaccination with H3N2 Influenza Viruses in Pre-Immune Individuals: Studies in the Pig Model

Abstract

In a previous study in influenza-naïve pigs, heterologous prime-boost vaccination with monovalent, adjuvanted whole inactivated vaccines (WIV) based on the European swine influenza A virus (SwIAV) strain, A/swine/Gent/172/2008 (G08), followed by the US SwIAV strain, A/swine/Pennsylvania/A01076777/2010 (PA10), was shown to induce broadly cross-reactive hemagglutination inhibition (HI) antibodies against 12 out of 15 antigenically distinct H3N2 influenza strains. Here, we used the pig model to examine the efficacy of that particular heterologous prime-boost vaccination regimen, in individuals with pre-existing infection-immunity. Pigs were first inoculated intranasally with the human H3N2 strain, A/Nanchang/933/1995. Seven weeks later, they were vaccinated intramuscularly with G08 followed by PA10 or vice versa. We examined serum antibody responses against the hemagglutinin and neuraminidase, and antibody-secreting cell (ASC) responses in peripheral blood, draining lymph nodes, and nasal mucosa (NMC), in ELISPOT assays. Vaccination induced up to 10-fold higher HI antibody titers than in naïve pigs, with broader cross-reactivity, and protection against challenge with an antigenically distant H3N2 strain. It also boosted ASC responses in lymph nodes and NMC. Our results show that intramuscular administration of WIV can lead to enhanced antibody responses and cross-reactivity in pre-immune subjects, and recall of ASC responses in lymph nodes and NMC.

Alternating 3 different influenza vaccines for swine in Europe for a broader antibody response and protection

“…In the case of group 3xMOV, pigs were challenged with a heterologous swIAV of the same HA subtype as the vaccine strain, a situation that is believed to predispose for “vaccine-associated enhanced respiratory disease” (VAERD) [ 66 ]. However, in line with other European swine vaccination studies [ 18 , 21 – 24 , 52 , 53 ], there were no significant differences in macroscopic lesion scores and histopathological findings among groups. As to group 3xMOV, the VAERD phenomenon might have been abrogated by the NI antibodies against G18 [ 67 ].…”

“…As an example, our data support the use of a multivalent vaccine (TIV or BIV), instead of the monovalent MOV vaccine, for the third vaccination, as this may boost antibody titers against H3 and human-like H1 swIAVs. Combinations of European and North American swIAV vaccines would results in an increased genetic and antigenic distance between vaccine strains and might also broaden the antibody responses [ 52 , 53 ] (Chepkwony et al, unpublished observations). Finally, prime-boost regimens with a LAIV followed by a WIV booster were shown to result in higher T cell responses than 2 WIV administrations [ 31 ].…”

Respiratory and Intramuscular Immunization With ChAdOx2-NPM1-NA Induces Distinct Immune Responses in H1N1pdm09 Pre-Exposed Pigs

“…Few studies have evaluated the immunological impact of prior influenza exposure on vaccine efficacy in large animal models. Chepkwony et al demonstrated that prior H3N2 exposure followed by intramuscular immunization with whole inactivated heterologous H3N2 vaccine induced stronger and broader antibody responses (43). Ferrets with pre-existing immune responses influenced recombinant H2 antibodies following vaccination (44).…”

Respiratory and intramuscular immunization with ChAdOx2 NPM1-NA induces distinct immune responses in H1N1pdm09 pre-exposed pigs

“…Few studies have evaluated the immunological impact of prior influenza exposure on vaccine efficacy in large animal models. Chepkwony et al demonstrated that prior H3N2 exposure followed by intramuscular immunization with whole inactivated heterologous H3N2 vaccine induced stronger and broader antibody responses 37 . Ferrets with pre-existing immune responses influenced recombinant H2 antibodies following vaccination 38 .…”