The type of adjuvant in whole inactivated influenza A virus vaccines impacts vaccine-associated enhanced respiratory disease

Authors: SOUZA, CARINE - Federal University Of Rio Grande; RAJÃO, DANIELA - Collaborator; SANDBULTE, MATTHEW - Iowa State University; LOPES, SARA - University Of Cambridge; LEWIS, NICOLA - University Of Cambridge; Loving, Crystal; GAUGER, PHILLIP - Iowa State University; Baker, Amy

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/28/2018
Publication Date: 10/1/2018
Citation: Souza, C.K., Rajão, D.S., Sandbulte, M.R., Lopes, S., Lewis, N.S., Loving, C.L., Gauger, P.C., Vincent, A.L. 2018. The type of adjuvant in whole inactivated influenza A virus vaccines impacts vaccine-associated enhanced respiratory disease. Vaccine. 36(41):6103-6110. https://doi.org/10.1016/j.vaccine.2018.08.072.
DOI: https://doi.org/10.1016/j.vaccine.2018.08.072

Interpretive Summary: Influenza A viruses (IAV) cause an important respiratory disease in pigs and a significant economic burden for the swine industry. Vaccines are commonly used in swine to protect against IAV but are often ineffective due to the diversity in strains that circulate in U.S. pig populations. Vaccines can be formulated in various ways, but whole inactivated virus (WIV) with an additive called adjuvants are the traditional vaccine for use in swine. One type of adjuvant, an oil-in-water (OW) emulsion, is commonly used in the swine industry, but WIV-OW has been associated with vaccine enhanced respiratory disease (VAERD). VAERD leads to increased lung damage and occurs when the challenge strain is sufficiently different from vaccine strains. We studied different adjuvants combined with WIV to assess whether these vaccine additives could have a role in VAERD. The type of adjuvant in the WIV formulation played a significant role in the magnitude of immune response to homologous and antigenically similar IAV, but only OW was associated with VAERD. None of the adjuvants combined with WIV showed protection against the antigenically-distinct challenge virus. These results highlight the impact adjuvant can have on vaccine effectiveness and provide important information for improving vaccines against IAV for use in swine.

Technical Abstract: Influenza A virus (IAV) causes a disease burden in the swine industry in the US and is a challenge to prevent due to substantial genetic and antigenic diversity of IAV that circulate in pig populations. Whole inactivated virus (WIV) vaccines formulated with oil-in-water (OW) adjuvant are commonly used in swine. However, WIV-OW are associated with vaccine-associated enhanced respiratory disease (VAERD) when the hemagglutinin and neuraminidase of the vaccine strain are mismatched with the challenge virus. Here, we assessed if different types of adjuvant in WIV vaccine formulations impacted VAERD outcome. Pigs were vaccinated with WIV with a swine delta1-H1N2, formulated with different commercial adjuvants: OW1, OW2, nano-emulsion squalene-based (NE), and gel polymer (GP). Pigs were vaccinated twice by the intramuscular route, 3 weeks apart, then challenged with an H1N1pdm09 three weeks post-boost, and necropsied at 5 days post infection. All WIV vaccines elicited antibodies detected using the hemagglutination inhibition (HI) assay against the homologous vaccine virus, but not against the heterologous challenge virus; in contrast, all vaccinated groups had cross-reactive IgG antibody and IFN-gamma responses against H1N1pdm09, with a higher magnitude observed in OW groups. Both OW groups demonstrated robust homologous HI titers and cross-reactivity against heterologous H1 viruses in the same genetic lineage. However, both OW groups had severe immunopathology consistent with VAERD after challenge when compared to NE, GP, and non-vaccinated challenge controls. None of the WIV formulations protected pigs from heterologous virus replication in the lungs or nasal cavity. Thus, although the type of adjuvant in the WIV formulation played a significant role in the magnitude of immune response to homologous and antigenically similar H1, none tested here increased the breadth of protection against the antigenically-distinct challenge virus, and some impacted immunopathology after challenge.