Abstract
We documented earlier that Mw (heat-killed suspension of Mycobacterium indicus pranii) adjuvant when used with conserved antigens, nucleoprotein (NP), and ectodomain of matrix (M2) protein (M2e) provided complete protection against homologous (clade 2.2) virus challenge in mice. The present study extends these observations to inter-clade challenge (clade 2.3.2.1) H5N1 virus and attempts to understand preliminary immunologic basis for the observed protection. Female BALB/c mice immunized with a single or two doses of vaccine formulations (clade 2.2 antigens) were challenged with 100LD50 homologous or heterologous (clade 2.3.2.1) virus. To understand the preliminary immunologic mechanism, we studied proportions of selected immune cell types, immune response gene expression, and Th1/Th2 cytokines induced by antigen-stimulated splenocytes from immunized mice, at different time points. Complete protection was conferred by Mw-HA, Mw-HA + NP, and Mw-HA + NP + M2e against homologous challenge. The protection correlated with IgG2a antibody titers indicating important role of Th1 response. Despite high inter-cladal antigenic differences, complete protection against the heterologous strain was achieved with Mw-HA + NP + M2e. Of note, a single dose with higher antigen concentrations (50 µg HA + 50 μg NP + 50 μg M2e) led to 80% protection against clade 2.3.2.1 strain. The protection conferred by Mw-HNM correlated with induction of IFN-γ, CD8+ T cytotoxic cells, and CD4+ T helper cells. Mw-adjuvanted HA + NP + M2e combination represents a promising vaccine candidate deserving further evaluation.
Highlights
Pathogenic and rapidly evolving avian influenza virus, H5N1, remains a pandemic threat
Since the aim of this study was to assess the efficacy of different vaccine formulations against the challenge of H5N1 virus, euthanasia was not used till experimental endpoint [post infection day 14 (PID-14)] to find out if reversal of sickness occurs resulting into survival
Due to ever-changing influenza virus genome and a potential threat of a pandemic with H5N1 virus causing high mortality, there is a definite need for a broad-spectrum vaccine that can be produced rapidly in large quantities and economically viable
Summary
Pathogenic and rapidly evolving avian influenza virus, H5N1, remains a pandemic threat. Use of antiviral drugs for the treatment of influenza has limitations because of the emergence of drug-resistant strains. Efficacy of Mw-Adjuvanted H5N1 Vaccine of H5N1 virus [3, 4]. Evolution of H5N1 virus genetically and antigenically in 10 diversified clades (clade 0–9) [5] underscores the need for a broadly cross-reactive vaccine. Available influenza vaccines mainly rely on HA antigens that do not offer protection against antigenically drifted strains [6]. The use of the conserved proteins of the virus such as nucleoprotein (NP) and M protein was considered for the generation of broadly reactive immune response and most desired “universal vaccine” [7, 8]. Lower immunogenicity of these proteins demands the use of potent adjuvants
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