Live Vector-Based Prophylactic Strategy Against Avian Influenza Virus in Chickens

Lahiri, Aritraa (2021) Live Vector-Based Prophylactic Strategy Against Avian Influenza Virus in Chickens. PhD thesis, Indian Institute of Science Education and Research Kolkata.

Text (PhD thesis of Aritraa Lahiri (13IP005)) 13IP005.pdf - Submitted Version Restricted to Repository staff only Download (5MB)

Abstract

The avian influenza virus (AIV) has drawn significant attention as an emerging zoonotic pathogen due to its potential to cause outbreaks in avian species as well as humans incurring a high mortality rate. However, the strategies currently available to control AIV infection in chickens, such as vaccines based on the major surface glycoprotein Haemagglutinin (HA) of the virus, are limited both in number and efficacy due to frequent antigenic drift and occasional shift of the segmented genome of these Type A influenza viruses. In contrast, Neuraminidase (NA), the second most abundant surface glycoprotein present in viral capsid, is less mutable and in some instances successful in eliciting inter-species cross-reactive antibody responses. However, NA based vaccines cannot singularly address the risk of virus escape from host defence. To this end, the highly conserved ectodomain of influenza Matrix Protein-2 (M2e) has emerged as an attractive vaccine target. In the present study, we are thus interested in investigating the plausible benefit of a vaccine composition that includes the M2e and NA as the antigenic components. Additionally, there remains a long pursuit of a more straightforward, safe and efficacious vaccine delivery vehicle against influenza infection. Considering the mucosal surfaces as primary portal of entry and transmission for AIV, very few attempts have been made to extrapolate the benefit of immunization through mucosal route. Contextually, Lactic acid producing bacteria (LAB) competent at expressing heterologous antigens have emerged as a promising platform for non-invasive, adjuvant free mucosal vaccine delivery. Thus, with the purpose of developing suitable mucosal vaccine candidates against avian influenza virus infection in chickens, this study describes the potential of a food-grade LAB (Lactococcus lactis subsp. cremoris, strain NZ9000) expressing functional AIV antigens, the NA or M2e, in conferring effective mucosal and systemic immune responses in the intestine as well as upper respiratory tracts of chickens. In addition, protein-specific sIgA obtained from the lavages collected from the trachea and intestine of the birds administered with rL. lactis were found to protect Madin-Darby Canine Kidney (MDCK) cells against influenza type A/PR/8/34 virus infection in vitro. It was also demonstrated that the rL. lactis orally delivered in chickens retained their ability to survive in a harsh gut environment without establishing persistent colonization. Moreover, some minor differences in the transcriptional profile of major pro-inflammatory cytokine genes was observed in the birds administered with either empty or rL. lactis. This could be attributed to the activation of innate response by L. lactis, advocating for its natural adjuvant capacity. Together, these results suggest oral administration of rL. lactis expressing influenza proteins may prove to be a promising vaccine approach against Type A influenza infections in chickens.

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