Journal Article

Cross-protective efficacy of bivalent recombinant baculoviral vaccine against heterologous influenza H5N1 challenge

Kwang, Jimmy, Prabakaran, Mookkan, Kolpe, Annasaheb B., He, Fang

2013

Overview

► Construction of baculovirus displayed HAs of A/Indonesia/669/06 and A/Anhui/01/05. ► Bivalent-BacHA induced humoral, cellular and mucosal immunity. ► Cross-protective efficacy of bivalent-BacHA against H5N1 clades. ► Oral delivery of bivalent-BacHA for pre pandemic vaccine. The present study demonstrates the cross-protective efficacy of baculovirus displayed HAs of A/Indonesia/669/06 and A/Anhui/01/05 against heterologous H5N1 challenges in a mouse model. Mice orally or subcutaneously immunized with live bivalent-BacHA vaccine significantly induced higher HA-specific humoral and cellular immune responses when compared with inactivated bivalent-BacHA. In addition, oral administration of live bivalent-BacHA vaccine was able to induce significant level of antigen-specific mucosal IgA levels. Microneutralization assay indicated that live bivalent-BacHA vaccine was able to induce strong cross-clade neutralization titer against distinct H5N1 clades (1, 2.1.3, 2.2.1.1, 2.3.2, 2.3.4, 4, 7 and 9). The production of both interferon-gamma (IFN-γ) and interleukin-4 (IL-4) by splenocytes from vaccinated mice indicated that mice vaccinated orally or subcutaneously with live bivalent-BacHA stimulated both IFN-γ secreting Th1 cells and IL-4 secreting Th2 cells, whereas mice immunized subcutaneously with inactive adjuvanted bivalent-BacHA stimulated only IL-4 secreting Th2 cells. Cross-protective immunity study also showed that mice immunized either orally or subcutaneously with live bivalent-BacHA were completely protected against 5MLD50 of clade 1 and clade 2.2.1.1 H5N1 viral infections. The protective immune response elicited by bivalent-BacHA vaccine against H5N1 variants demonstrates the possibility of protection against a broad range of H5N1 strains.

• Publisher: Elsevier Ltd,Elsevier,Elsevier Limited
• Subject: Administration, Oral / Allergy and Immunology / animal models / Animals / Antibodies, Neutralizing - blood / Antibodies, Viral - blood / Applied microbiology / Avian flu / BacHA / Baculoviridae / Baculoviridae - genetics / Baculovirus / Biological and medical sciences / cell-mediated immunity / Cellular immunity / Cross Protection / Cross-protective / Disease Models, Animal / Drug Carriers / Female / Fundamental and applied biological sciences. Psychology / Genetic Vectors / H5N1 / Hemagglutinin Glycoproteins, Influenza Virus - genetics / Hemagglutinin Glycoproteins, Influenza Virus - immunology / immune response / Immune system / immunoglobulin A / Infections / influenza / Influenza A Virus, H5N1 Subtype - genetics / Influenza A Virus, H5N1 Subtype - immunology / Influenza Vaccines - administration & dosage / Influenza Vaccines - genetics / Influenza Vaccines - immunology / Injections, Subcutaneous / interferon-gamma / Interferon-gamma - secretion / interleukin-4 / Laboratories / Medical research / Mice / Mice, Inbred BALB C / Microbiology / Miscellaneous / neutralization / oral administration / oral vaccination / Oral vaccine / Orthomyxoviridae Infections - immunology / Orthomyxoviridae Infections - prevention & control / Orthomyxoviridae Infections - virology / Pre-pandemic / Rodents / splenocytes / T-Lymphocytes - immunology / Vaccines / Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects) / Vaccines, Synthetic - administration & dosage / Vaccines, Synthetic - genetics / Vaccines, Synthetic - immunology / Virology / Viruses