Prediction of highly pathogenic avian influenza vaccine efficacy in chickens by comparison of in vitro and in vivo data: a meta-analysis and systematic review

Authors: MO, JONGSEO - Orise Fellow; Spackman, Erica; Swayne, David

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/31/2023
Publication Date: 8/31/2023
Citation: Mo, J., Spackman, E., Swayne, D.E. 2023. Prediction of highly pathogenic avian influenza vaccine efficacy in chickens by comparison of in vitro and in vivo data: a meta-analysis and systematic review. Vaccine. 41(38):5507-5517. https://doi.org/10.1016/j.vaccine.2023.07.076.
DOI: https://doi.org/10.1016/j.vaccine.2023.07.076

Interpretive Summary: Vaccination can be an effective tool to help manage the spread of bird flu and can prevent disease in poultry. To learn how to better predict how well vaccines will work against a particular field strain, a study was conducted to compile data from all available studies in the literature. We searched for studies that evaluated bird flu in chickens using the most common vaccine types and which reported antibody quantities from the vaccine and quantities of virus excretion. Using standard statistical methods the data from all comparable studies were compiled to determine what minimum antibody levels would provide protection against death and would substantially limit virus excretion. In addition to antibody levels, the genetic relationship between the vaccine and the challenge virus were evaluated for the same results. It was found that most vaccines could provide protection from death and would decrease virus excretion even when antibody levels were very low. In contrast, vaccine types varied in how related they needed to be in order to provide protection and decrease virus excretion. Inactivated vaccines needed to be more closely related to the challenge virus than vectored vaccines (which are vaccines that use material from bird flu and a harmless carrier virus to induce immunity).

Technical Abstract: Vaccines for avian influenza (AI) can protect poultry against disease, mortality, and virus transmission. Numerous factors, including: vaccine platform, immunogenicity, and relatedness to the field strain, are known to be important to achieving optimal AI vaccine efficacy. To better understand how these factors contribute to vaccine protection, a systematic meta-analysis was conducted to evaluate efficacy data for vaccines in chickens challenged with highly pathogenic (HP) AI. Data from a total of 120 individual trials from 25 publications were selected and evaluated. Two vaccine criteria were evaluated for their effects on two metrics of protection. The vaccine criteria were: 1) the relatedness of the vaccine antigen and challenge strain in the hemagglutinin 1 domain (HA1) protein sequence; 2) vaccine-induced antibody titers to the challenge virus (VIAC). The metrics of protection were: A) survival of vaccinated chickens vs unvaccinated controls; and B) reduction in oral virus-shedding by vaccinated vs unvaccinated controls 2–4 days post challenge. Three vaccine platforms were evaluated: oil-adjuvanted inactivated whole AI virus, recombinant herpes virus of turkeys (rHVT) vectored, and a non-replicating alpha-virus vectored RNA particle (RP) vaccine. Higher VIAC correlated with greater reduction of virus-shed and vaccine efficacy by all vaccine platforms. Both higher HA1 relatedness and higher VIAC using challenge virus as antigen correlated with better survival by inactivated vaccines and rHVT-vectored vaccines. However, rHVT-vectored and RP based vaccines were more tolerant of variation in the HA1; the relatedness of the HA1 of the vaccine and challenge virus did not significantly correlate with survival with rHVT-vectored vaccines. Protection was achieved with the lowest aa similarity for which there was data, 90–93 % for rHVT vaccines and 88 % for the RP vaccine.