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

Abstract

There is a critical need to develop superior influenza vaccines that provide broader protection. Influenza vaccines are traditionally tested in naive animals, although humans are exposed to influenza in the first years of their lives, but the impact of prior influenza exposure on vaccine immune responses has not been well studied. Pigs are an important natural host for influenza, are a source of pandemic viruses, and are an excellent model for human influenza. Here, we investigated the immunogenicity of the ChAdOx2 viral vectored vaccine, expressing influenza nucleoprotein, matrix protein 1, and neuraminidase in H1N1pdm09 pre-exposed pigs. We evaluated the importance of the route of administration by comparing intranasal, aerosol, and intramuscular immunizations. Aerosol delivery boosted the local lung T-cell and antibody responses, while intramuscular immunization boosted peripheral blood immunity. These results will inform how best to deliver vaccines in order to harness optimal protective immunity.

Immunization with matrix-, nucleoprotein and neuraminidase protects against H3N2 influenza challenge in pH1N1 pre-exposed pigs

“…Twenty pigs were infected intranasally with 3 × 10 6 PFU of A/swine/England/1353/2009 (pH1N1). All pigs were successfully infected and shed virus as determined by plaque assays of daily nasal swabs in the first 6 days following pH1N1 inoculation 34 . Four weeks after the pH1N1 inoculation, the pigs were randomly divided into four groups of five animals and were immunized with 5 × 10 8 IU ChAdOx2-NPM1-NA2 intramuscularly (IM), intranasally (IN) or by aerosol (AE) as previously described 34 .…”

“…We have also evaluated the importance of route of administration by comparing intra-nasal, aerosol and intra-muscular immunization. In these studies, aerosol delivery boosted the local lung T cell and antibody responses, while intra-muscular immunization boosted peripheral blood immunity 34 . However, protective efficacy was not evaluated and therefore in the present study we assessed the immunogenicity and efficacy of prime boost with ChAdOx2-NPM1-NA2 and MVA-NPM1-NA2 administered by the intra-muscular, intra-nasal or aerosol routes in pH1N1 pre-exposed pigs against H3N2 challenge.…”

“…Because pigs are susceptible to the influenza A viruses that infect humans, we have developed an H1N1pdm09 (pH1N1) 1A.3.3.2 virus pre-exposure model to test the immunogenicity of a ChAdOx2 viral vectored vaccine, expressing influenza nucleoprotein, matrix protein 1 from pH1N1 and neuraminidase NA2 from A/swine/Ohio/A01354299/2017, H3N2 (ChAdOx2-NPM1-NA2) 34 . We have shown that previous influenza virus pH1N1 infection in pigs does not prevent induction of immune responses following immunization with ChAdOx2-NPM1-NA2 34 . We have also evaluated the importance of route of administration by comparing intra-nasal, aerosol and intra-muscular immunization.…”

How Do Anti-SARS-CoV-2 mRNA Vaccines Protect from Severe Disease?

“…In particular, the intramuscular injection of an anti-Respiratory Syncytial Virus vaccine elicited immunities in both the nose and lungs showing identical anti-viral efficacies [ 11 ]. In addition, the intramuscular injection of an adenoviral vector-based anti-flu vaccine induced quite balanced humoral and cellular anti-viral immune responses in the upper and lower respiratory tracts [ 12 ]. Hence, it remains unclear why, on the contrary, anti-SARS-CoV-2 vaccines would induce such unbalanced antiviral immune responses in different respiratory districts.…”

“…In fact, the vaccine-induced immune stimulus is provided peripherally by the intramuscular injection. Hence, the quality and extent of the vaccine-induced anti-Spike protein immunity responses are expected to be similar in the upper and lower respiratory tracts [ 11 , 12 ].…”