Giuseppe
Emeritus
Gastrointestinal delivery of baculovirus displaying influenza hemagglutinin protects mice against heterologous H5N1 infection. (J Virol., abstract)
J Virol. 2010 Jan 13. [Epub ahead of print]
Gastrointestinal delivery of baculovirus displaying influenza hemagglutinin protects mice against heterologous H5N1 infection.
Prabakaran M, Madhan S, Prabhu N, Qiang J, Kwang J. - Animal Health Biotechnology, Temasek Life Sciences Laboratory, National University of Singapore, Singapore, 117604; Department of Microbiology, Faculty of Medicine, National University of Singapore, Singapore.
The recent outbreaks of influenza A H5N1 in birds and humans have necessitated the development of potent H5N1 vaccines. In this study, we evaluated the protective potential of immediate early promoter-based baculovirus displaying HA (BacHA) against HPAI H5N1 infection in a mouse model. Gastrointestinal delivery of BacHA significantly enhanced systemic immune response in terms of HA specific serum IgG and hemagglutination inhibition titers. In addition, BacHA vaccine was able to significantly enhance mucosal IgA level. The inclusion of recombinant cholera toxin B subunit as a mucosal adjuvant along with BacHA vaccine did not influence both the systemic and mucosal immunity. Interestingly, inactivated form of BacHA was able to induce only negligible level of immune responses, when compared to its live counterpart. Microneutralization assay also indicated that live BacHA vaccine was able to induce strong cross-clade neutralization against heterologous H5N1 strains (clade 1.0, clade 2.1 and clade 8.0) compared to the inactivated BacHA. Viral challenge studies showed that live BacHA was able to provide 100% protection against 5MLD50 of homologous (Clade 2.1) and heterologous (Clade 1) H5N1 infection. Moreover, histopathological examinations revealed that mice vaccinated with live BacHA had only minimal bronchitis in lungs and regained their body weight more rapidly post challenge. Furthermore, immunohistochemistry results demonstrated that the live BacHA was able to transduce and express HA in the intestinal epithelial cells in vitro and in vivo. We have demonstrated that recombinant baculovirus with a WSSV ie1 promoter have acted as a vector as well as a protein vaccine and will enable the rapid production of pre-pandemic and pandemic vaccines without any biosafety concerns.
PMID: 20071572 [PubMed - as supplied by publisher]
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J Virol. 2010 Jan 13. [Epub ahead of print]
Gastrointestinal delivery of baculovirus displaying influenza hemagglutinin protects mice against heterologous H5N1 infection.
Prabakaran M, Madhan S, Prabhu N, Qiang J, Kwang J. - Animal Health Biotechnology, Temasek Life Sciences Laboratory, National University of Singapore, Singapore, 117604; Department of Microbiology, Faculty of Medicine, National University of Singapore, Singapore.
The recent outbreaks of influenza A H5N1 in birds and humans have necessitated the development of potent H5N1 vaccines. In this study, we evaluated the protective potential of immediate early promoter-based baculovirus displaying HA (BacHA) against HPAI H5N1 infection in a mouse model. Gastrointestinal delivery of BacHA significantly enhanced systemic immune response in terms of HA specific serum IgG and hemagglutination inhibition titers. In addition, BacHA vaccine was able to significantly enhance mucosal IgA level. The inclusion of recombinant cholera toxin B subunit as a mucosal adjuvant along with BacHA vaccine did not influence both the systemic and mucosal immunity. Interestingly, inactivated form of BacHA was able to induce only negligible level of immune responses, when compared to its live counterpart. Microneutralization assay also indicated that live BacHA vaccine was able to induce strong cross-clade neutralization against heterologous H5N1 strains (clade 1.0, clade 2.1 and clade 8.0) compared to the inactivated BacHA. Viral challenge studies showed that live BacHA was able to provide 100% protection against 5MLD50 of homologous (Clade 2.1) and heterologous (Clade 1) H5N1 infection. Moreover, histopathological examinations revealed that mice vaccinated with live BacHA had only minimal bronchitis in lungs and regained their body weight more rapidly post challenge. Furthermore, immunohistochemistry results demonstrated that the live BacHA was able to transduce and express HA in the intestinal epithelial cells in vitro and in vivo. We have demonstrated that recombinant baculovirus with a WSSV ie1 promoter have acted as a vector as well as a protein vaccine and will enable the rapid production of pre-pandemic and pandemic vaccines without any biosafety concerns.
PMID: 20071572 [PubMed - as supplied by publisher]
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