Abstract
Neuraminidase is an important target for influenza vaccination. In this study, we generated avian influenza VLPs, expressing hemagglutinin (HA), neuraminidase (NA), HA and NA co-expressed (HANA), to evaluate the protective role of NA against a high (10LD50) and low (2LD50) dose of avian influenza virus challenge infections. A single immunization with HANA VLPs elicited the highest level of virus-specific IgG, IgG1, and IgG2a responses from the sera post-vaccination and the lungs post-challenge-infection. Potent antibody-secreting cell responses were observed from the spleens and lungs of HANA-VLP-immunized mice post-challenge-infection. HANA VLPs induced the highest CD4+ T cell, CD8+ T cell, and germinal center B cells, while strongly limiting inflammatory cytokine production in the lungs compared to other VLP immunization groups. In correlation with these findings, the lowest bodyweight losses and lung virus titers were observed from HANA VLP immunization, and all of the immunized mice survived irrespective of the challenge dose. Contrastingly, VLPs expressing either HA or NA alone failed to elicit complete protection. These results indicated that NA in VLPs played a critical role in inducing protection against a high dose of the challenge infection.
Highlights
Pathogenic avian influenza viruses such as the H5N1 subtype are a major threat to humans and other animals
Hemagglutinin (HA), neuraminidase (NA), and matrix 1 protein (M1) genes were cloned into the pFastBac vector and cleaved with restriction enzymes
HA antigens were only detected from HA and HA and NA co-expressed (HANA) virus-like particles (VLPs), whereas NA antigen expression was only observed from NA and HANA VLPs
Summary
Pathogenic avian influenza viruses such as the H5N1 subtype are a major threat to humans and other animals. Only a few VLP-based vaccine studies involving avian NA antigens have been conducted [12,13,14] While these aforementioned studies delineated that VLPs co-expressing both HA and NA are efficacious, many of the NA-VLP-induced immune correlates associated with protection were not investigated. Infection dose is another factor that must be taken into consideration in vaccine studies, as evidenced by the presence of a strong correlation between infection dose and disease severity for influenza viruses. Findings presented here provide vital information for the avian influenza vaccine design strategy that can be utilized to control avian influenza outbreaks
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