Efficacy of inactivated and RNA particle vaccines against a North American clade 2.3.4.4b H5 highly pathogenic avian influenza virus

Authors: Spackman, Erica; Suarez, David; Lee, Chang; Pantin Jackwood, Mary; Lee, Scott; YOUK, SUNGSU - Chungbuk National University College Of Medicine; IBRAHIM, SHERIF - Orise Fellow

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/27/2023
Publication Date: 11/4/2023
Citation: Spackman, E., Suarez, D.L., Lee, C.W., Pantin Jackwood, M.J., Lee, S.A., Youk, S., Ibrahim, S. 2023. Efficacy of inactivated and RNA particle vaccines against a North American clade 2.3.4.4b H5 highly pathogenic avian influenza virus. Vaccine. 41(49):7369-7376. https://doi.org/10.1016/j.vaccine.2023.10.070.
DOI: https://doi.org/10.1016/j.vaccine.2023.10.070

Interpretive Summary: Bird flu is a deadly disease for chickens and turkeys; it can wipe out a flock within a few days. Vaccines can prevent disease and can even reduce spread among poultry flocks. Several vaccines for bird flu have been licensed in the United States including a "killed" virus product called rgH5N1, and a second vaccine, called RP, that uses an innocuous carrier virus to deliver the protein that induces immunity to bird flu. Because the bird flu virus can mutate over time to escape the immune system, vaccines need to be tested periodically to ensure that they will work against the current viruses in the field. Therefore, we tested the RP vaccine, the rgH5N1 vaccine, and two in-house produced vaccines that use a killed virus similar to the rgH5N1 vaccine. The four vaccines were tested in chickens and all completely protected the birds from disease and death. All four vaccines also reduced the quantity of virus excreted by the chickens to varying degrees. Finally, an antibody based test was evaluated to determine whether birds that were vaccinated then exposed to virus, could be identified. This is a critical component of a surveillance program to ensure that vaccines don't "mask" infection in poultry. It was found that the antibody test could detect infection as early as seven days after exposure in all of the RP vaccinated chickens and in 70% of the chickens vaccinated with an in-house vaccine.

Technical Abstract: Highly pathogenic avian influenza virus (HPAIV) has caused a widespread outbreak in poultry in the Americas. Because of the duration and extent of this outbreak, vaccine use may be an additional tool to limit virus spread. Four vaccines were evaluated for efficacy in chickens against a current North American clade 2.3.4.4b HPAIV isolate, A/turkey/Indiana/3703-003/2022 H5N1 (TK/IN/22), using an established challenge model. The vaccines included: 1) a commercial inactivated reverse genetics (rg) generated H5N1 product with a clade 2.3.4.4c H5 hemagglutinin (HA) (rgH5N1); 2) a commercial alphavirus RNA particle (RP) vaccine with the TK/IN/22 HA; 3) an in-house inactivated rg vaccine with the TK/IN/22 HA (SEP-22-N1); and 4) an in-house inactivated rg produced vaccine with the TK/IN/22 HA and a North American wild bird N9 neuraminidase (NA) (SEP-22-N9). All three inactivated vaccines were produced with HA genes that were modified to be low pathogenic and were produced with the remaining genes from the PR8 influenza A strain. All four vaccines provided 100% protection against mortality and morbidity. However, differences were observed among the vaccines in quantities of virus shed by the oropharyngeal (OP) and cloacal (CL) routes at 2 and 4 days post challenge (DPC). At 2DPC all four vaccines reduced OP and CL shed significantly compared to sham vaccinates. In general, SEP-22-N1 and SEP-22-N9 reduced virus shed the most by both routes and the RP vaccine reduced shed the least, which was only significantly different from the SEP vaccines at 2DPC by the OP route and 4DPC by the OP and CL routes. The rgH5N1 vaccine group shed intermediate quantities of virus which was only significantly higher than SEP-22-N1 and SEP-22-N9 by the oral route at 4DPC. Serum was collected from the RP and SEP-22-N9 vaccine groups at 7, 10, and 14 DPC to detect antibody to the NA and nucleoprotein (NP) of the challenge virus by enzyme linked lectin assay (ELLA) and ELISA. As early as 7DPC ELLA detected antibody in sera from 100% of the chickens in the RP vaccinated group and 70% of the chickens in the SEP-22-N9 vaccinated group, which reflects the difference in virus replication between the two vaccine groups. Antibody to the NP was detected by commercial ELISA in more than 50% of the birds in the RP vaccinated group at each time point.