Immunogenicity and Protective Efficacy of a Recombinant Pichinde Viral-Vectored Vaccine Expressing Influenza Virus Hemagglutinin Antigen in Pigs

Abstract

Influenza A virus of swine (IAV-S) is an economically important swine pathogen. The IAV-S hemagglutinin (HA) surface protein is the main target for vaccine development. In this study, we evaluated the feasibility of using the recombinant tri-segmented Pichinde virus (rPICV) as a viral vector to deliver HA antigen to protect pigs against IAV-S challenge. Four groups of weaned pigs (T01–T04) were included in the study. T01 was injected with PBS to serve as a non-vaccinated control. T02 was inoculated with rPICV expressing green fluorescence protein (rPICV-GFP). T03 was vaccinated with rPICV expressing the HA antigen of the IAV-S H3N2 strain (rPICV-H3). T04 was vaccinated with the recombinant HA protein antigen of the same H3N2 strain. Pigs were vaccinated twice at day 0 and day 21 and challenged at day 43 by intra-tracheal inoculation with the homologous H3N2 IAV-S strain. After vaccination, all pigs in T03 and T04 groups were seroconverted and exhibited high titers of plasma neutralizing antibodies. After challenge, high levels of IAV-S RNA were detected in the nasal swabs and bronchioalveolar lavage fluid of pigs in T01 and T02 but not in the T03 and T04 groups. Similarly, lung lesions were observed in T01 and T02, but not in the T03 and T04 groups. No significant difference in terms of protection was observed between the T03 and T04 group. Collectively, our results demonstrate that the rPICV-H3 vectored vaccine elicited protective immunity against IAV-S challenge. This study shows that rPICV is a promising viral vector for the development of vaccines against IAV-S.

Assessment of Immune Responses to a Trivalent Pichinde Virus-Vectored Vaccine Expressing Hemagglutinin Genes from Three Co-Circulating Influenza A Virus Subtypes in Pigs

“…The vaccination and challenge experiment were conducted in a weaned pig’s model, as described previously [ 43 ]. Twenty-one 4-week-old pigs, seronegative for IAV-S and PRRSV, were obtained from Midwest Swine Research.…”

“…IAV-S RNA extraction and quantification from nasal swabs and BALF samples were performed as previously described [ 43 ]. Viral loads were reported as log 10 copies of IAV RNA per 100 μL of sample used to extract RNA.…”

“…In a previous study, we demonstrated that a monovalent PICV-vectored vaccine expressing the HA gene of the H3N2 virus induced high titers of virus-neutralizing and hemagglutination inhibition antibodies and protected pigs against a subsequent challenge from the homologous H3N2 virus [ 43 ]. In the present study, we demonstrated that pigs vaccinated with a trivalent PICV expressing representative HA genes from three co-circulating IAV-S strains mounted robust immune responses against all three antigens, and were protected against challenge infection with the homologous H1N1 strain.…”

Swine influenza A virus: challenges and novel vaccine strategies

“…Pichinde virus (PICV) is a bisegmented and enveloped RNA virus within the family Arenaviridae . PICV was first isolated from rice rats in Colombia ( Mclay et al., 2014 ) but can infect a wide range of cell types from humans, mice, monkeys, birds, and pigs ( Dhanwani et al., 2015 , 2017 ; Kumar et al., 2021 ; Kumari et al., 2022 ). Initial studies in mice demonstrated that PICV encoding the HA and NP proteins of A/Puerto Rico/8/34 protected mice against lethal IAV infection after two immunizations.…”

“…After homologous challenge, rPICV-H3 immunized pigs showed significantly reduced viral shedding from nasal secretions, no infectious virus recovered from the lungs, and minimal macroscopic or microscopic lung lesions compared to sham vaccinated animals. Further, pigs vaccinated with recombinant PICV encoding GFP (rPICV-GFP) did not horizontally transmit infectious rPICV to naive pigs ( Kumari et al., 2022 ). This indicates that PICV may be a safe platform for immunization against swine pathogens with limited risk of vector circulation.…”