Stockpiled pre-pandemic H5N1 influenza virus vaccines with AS03 adjuvant provide cross-protection from H5N2 clade 2.3.4.4 virus challenge in ferrets

Abstract

Avian influenza viruses, notably H5 subtype viruses, pose a continuous threat to public health due to their pandemic potential. In recent years, influenza virus H5 subtype split vaccines with novel oil-in-water emulsion based adjuvants (e.g. AS03, MF59) have been shown to be safe, immunogenic, and able to induce broad immune responses in clinical trials, providing strong scientific support for vaccine stockpiling. However, whether such vaccines can provide protection from infection with emerging, antigenically distinct clades of H5 viruses has not been adequately addressed. Here, we selected two AS03-adjuvanted H5N1 vaccines from the US national prepandemic influenza vaccine stockpile and assessed whether the 2004–05 vaccines could provide protection against a 2014 highly pathogenic avian influenza (HPAI) H5N2 virus (A/northern pintail/Washington/40964/2014), a clade 2.3.4.4 virus responsible for mass culling of poultry in North America. Ferrets received two doses of adjuvanted vaccine containing 7.5 μg of hemagglutinin (HA) from A/Vietnam/1203/2004 (clade 1) or A/Anhui/1/2005 (clade 2.3.4) virus either in a homologous or heterologous prime-boost vaccination regime. We found that both vaccination regimens elicited robust antibody responses against the 2004–05 vaccine viruses and could reduce virus-induced morbidity and viral replication in the lower respiratory tract upon heterologous challenge despite the low level of cross-reactive antibody titers to the challenge H5N2 virus. This study supports the value of existing stockpiled 2004–05 influenza H5N1 vaccines, combined with AS03-adjuvant for early use in the event of an emerging pandemic with H5N2-like clade 2.3.4.4 viruses.

Avian Influenza A Virus Pandemic Preparedness and Vaccine Development

“…Recent studies were performed to assess whether existing pre-pandemic stockpiled A/H5 vaccines could be used in heterologous prime-boost vaccination regimes to provide protection against the newly emerged divergent clade 2.3.4.4 viruses. Priming with AS03-adjuvanted split inactivated A/Vietnam/1203/2004 (clade 1) and boosting with A/Anhui/1/05 (clade 2.3.4) slightly improved the cross-reactivity with clade 2.3.4.4 viruses in ferrets compared to a homologous prime-boost regime, albeit without any statistical significance [ 40 ]. Similar heterologous prime-boost vaccination schemes were performed in humans (A/Vietnam/1203/2004 (clade 1) followed by A/Anhui/1/05 (clade 2.3.4)) which led to a modest level of HI antibodies cross-reactive with clade 2.3.4.4 viruses, while homologous prime-boost (A/Vietnam/1203/2004 (clade 1)) did not [ 41 ].…”

Usability of daily SF36 questionnaires to capture the QALD variation experienced after vaccination with AS03A-adjuvanted monovalent influenza A (H5N1) vaccine in a safety and tolerability study

“…The large amounts of antigen needed for these vaccine formulations therefore limits the global supply [3]. Adjuvantation of vaccines could overcome these issues, as adjuvanted vaccines may perform better since they have been shown to elicit a higher immune response compared with non-adjuvanted vaccines [3–5], and may in turn lead to better prevention against emerging, antigenically distinct clades of H5N1 [6], and specific infections [7]. Higher immunogenicity vaccines, however, have been shown to be associated with increased reactogenicity at the injection site (most commonly with pain and swelling) and systemic symptoms (usually with fatigue, muscle soreness and headaches) [8–10].…”

Pandemic Influenza Vaccines: What did We Learn from the 2009 Pandemic and are We Better Prepared Now?

“…Human trials and animal studies indicate that immunisation with A(H5N1) vaccines containing oil-in-water adjuvants increased the antibody response and was broader in cross-reactivity than immunisation with a vaccine without adjuvant ( [55], reviewed in [52]). As multiple doses of vaccine may be required to mount a protective immune response against some avian influenza viruses, immunising with a stockpiled H5/H7 vaccine, with (or without) adjuvant, may be useful to prime the immune response of individuals until a matched vaccine is available ( [56,57], reviewed in [52]).…”