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. 2022 Sep 9;40(38):5569-5578.
doi: 10.1016/j.vaccine.2022.07.042. Epub 2022 Aug 18.

Bivalent hemagglutinin and neuraminidase influenza replicon particle vaccines protect pigs against influenza a virus without causing vaccine associated enhanced respiratory disease

Meghan Wymore Brand  1 , Tavis K Anderson  1 , Pravina Kitikoon  2 , J Brian Kimble  1 , Nicholas Otis  1 , Phillip C Gauger  3 , Carine K Souza  1 , Bryan Kaplan  1 , Mark Mogler  4 , Erin Strait  2 , Amy L Vincent Baker  5
Affiliations
Free article

Bivalent hemagglutinin and neuraminidase influenza replicon particle vaccines protect pigs against influenza a virus without causing vaccine associated enhanced respiratory disease

Meghan Wymore Brand et al. Vaccine. .
Free article

Abstract

Alphavirus-derived RNA replicon particle (RP) vaccines represent the next generation of swine influenza A virus (IAV) vaccines, as they were shown to be safe, effective, and offer advantages over traditional vaccine platforms. IAV is a significant respiratory pathogen of swine and there is a critical need to improve current commercial swine IAV vaccine platforms. Adjuvanted whole inactivated virus (WIV) IAV swine vaccines provide limited heterologous protection and may lead to vaccine-associated enhanced respiratory disease (VAERD). This study investigated the ability of RP IAV hemagglutinin (HA) vaccines to avoid VAERD and evaluated experimental multivalent HA and neuraminidase (NA) RP vaccines. RP vaccines were formulated with HA or NA heterologous or homologous to the challenge virus in monovalent HA or HA and NA bivalent combinations (HA/NA bivalent). Pigs were vaccinated with an HA RP, HA/NA bivalent RP, or heterologous HA WIV, followed by IAV challenge and necropsy 5 days post infection. RP vaccines provided homologous protection from challenge and induced robust peripheral and local antibody responses. The RP vaccine did not induce VAERD after challenge with a virus containing the heterologous HA, in contrast to the traditional WIV vaccine. The HA monovalent and HA/NA bivalent RP vaccines showed superior protection compared to traditional WIV. Additionally, the RP platform allows greater flexibility to adjust HA and NA content to reflect circulating IAV in swine antigenic diversity.

Keywords: Influenza; RNA vaccine; Replicon particle; Swine; Vaccine Associated Enhanced Respiratory Disease (VAERD).

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Conflict of interest statement

Declaration of Competing Interest PK and MM are employees of Merck Animal Health, De Soto, KS, USA. ES was an employee of Merck Animal Health, De Soto, KS, USA and is now at Ceva Animal Health. Contributions AVB, TA, PK, and ES designed the study. MM prepared the RP vaccines. MWB, JBK, CKS, and AVB performed the animal studies. MWB, PG, NO, BK performed laboratory assays and data acquisition. MWB wrote the manuscript, and all authors approved the final version of the manuscript.

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