Efficacy of a recombinant turkey herpesvirus (H9) vaccine against H9N2 avian influenza virus in chickens with maternal-derived antibodies

Xue Pan; Qinfang Liu; Shiqi Niu; Dongming Huang; Dawei Yan; Qiaoyang Teng; Xuesong Li; Nancy Beerens; Maria Forlenza; Mart C M de Jong; Zejun Li

doi:10.3389/fmicb.2022.1107975

Efficacy of a recombinant turkey herpesvirus (H9) vaccine against H9N2 avian influenza virus in chickens with maternal-derived antibodies

Front Microbiol. 2023 Jan 26:13:1107975. doi: 10.3389/fmicb.2022.1107975. eCollection 2022.

Authors

Xue Pan^{1

2}, Qinfang Liu¹, Shiqi Niu¹, Dongming Huang¹, Dawei Yan¹, Qiaoyang Teng¹, Xuesong Li¹, Nancy Beerens³, Maria Forlenza⁴, Mart C M de Jong², Zejun Li¹

Affiliations

¹ Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China.
² Quantitative Veterinary Epidemiology, Animal Sciences Group, Wageningen University and Research, Wageningen, Netherlands.
³ Wageningen Bioveterinary Research, Wageningen University and Research, Lelystad, Netherlands.
⁴ Host-Microbe Interactomics Group, Animal Sciences Group, Wageningen University and Research, Wageningen, Netherlands.

Abstract

Although vaccines have been widely used for many years, they have failed to control H9N2 avian influenza virus (AIV) in the field in China. The high level of maternal-derived antibodies (MDAs) against H9N2 virus contributes to the H9N2 influenza vaccine failure in poultry. The study aimed to generate a new vaccine to overcome MDAs interference in H9N2 vaccination in chickens. We used turkey herpesvirus (HVT) as a vaccine vector to express H9 hemagglutinin (HA) proteins. The recombinant HVT expressing H9 HA proteins (rHVT-H9) was successfully generated and characterized in primary chicken embryonic fibroblasts (CEFs). Western blot and indirect immunofluorescence assay (IFA) showed that the rHVT-H9 consistently expressed HA proteins. In addition, the rHVT-H9 had similar growth kinetics to the parent HVT. Preliminary animal experiments showed that compared to the conventional inactivated whole virus (IWV) vaccine, the rHVT-H9 stimulated robust humoral immunity in chickens with passively transferred antibodies (PTAs) that were used to mimic MDAs. Transmission experiments showed that the rHVT-H9 induced both humoral and cellular immunity in chickens with PTAs. Furthermore, we used mathematical models to quantify the vaccine's efficacy in preventing the transmission of H9N2 AIV. The results showed that the rHVT-H9 reduced the virus shedding period and decreased the reproduction ratio (R) value in chickens with PTAs after homologous challenge. However, the vaccination in this trial did not yet bring R < 1. In summary, we generated a new rHVT-H9 vaccine, which stimulated strong humoral and cellular immunity, reducing virus shedding and transmission of H9N2 AIV even in the presence of PTAs in chickens.

Keywords: immune responses; maternal-derived antibodies; passively transferred antibodies; recombinant vaccine; transmission; turkey herpesvirus (HVT).