tetano
Editor, Senior Moderator
J Virol. 2014 Jun 11. pii: JVI.00823-14. [Epub ahead of print]
Intranasal adenovirus vectored vaccine for induction of long-lasting humoral immunity-mediated broad protection against influenza in mice.
Kim EH1, Park HJ1, Han GY1, Song MK1, Pereboev A2, Hong JS3, Chang J4, Byun YH5, Seong BL5, Nguyen HH6.
Author information
Abstract
Influenza vaccines aimed at inducing antibody (Ab) responses against viral surface hemagglutinin (HA) and neuraminidase (NA) provide sterile immunity to infection with the same subtypes. Vaccines targeting viral conserved determinants shared by the influenza A viruses (IAV) offer heterosubtypic immunity (HSI), a broad protection against different subtypes. We proposed that vaccines targeting both HA and the conserved ectodomain of matrix protein 2 (M2e) would provide protection against infection with the same subtype and also HSI against other subtypes. Here we report that single intranasal (i.n.) immunization with a recombinant adenovirus (rAd) vector encoding both HA of H5 virus and M2e (rAdH5/M2e) induced significant HA and M2e specific Ab responses along with protection against heterosubtypic challenge in mice. The protection is superior as compared to that induced by rAd vector encoding either HA (rAdH5), or M2e (rAdM2e). While protection against homotypic H5 virus is primarily mediated by virus neutralizing (VN) antibodies (Abs), the cross-protection is associated with Abs directed to conserved stalk HA and M2e that seem to have additive effect. Consistently, adoptive transfer of antisera induced by rAdH5/M2e provided the best protection against heterosubtypic challenge as compared to that provided by antisera derived from mice immunized with rAdH5 or rAdM2e. These results support the development of rAd vectored vaccines encoding both H5 and M2e as universal vaccines against different IAV subtypes.
IMPORTANCE:
Current licensed influenza vaccines provide protection limited to the infection with same virus strains, therefore, the composition of influenza vaccines has to be revised every year. We have developed a new universal influenza vaccine that is highly efficient in induction of long-lasting cross-protection against different influenza virus strains. The cross-protection is associated with high level of vaccine-induced antibodies against conserved stalk domain of influenza virus hemagglutinin and ectodomain of matrix protein. The vaccine could be used to stimulate cross-protective antibodies for prevention and treatment of influenza with immediate effect for individuals who fail to respond to or receive the vaccine in due time. The vaccine offers a new tool to control influenza outbreaks including pandemics.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
24920793
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24920793
Intranasal adenovirus vectored vaccine for induction of long-lasting humoral immunity-mediated broad protection against influenza in mice.
Kim EH1, Park HJ1, Han GY1, Song MK1, Pereboev A2, Hong JS3, Chang J4, Byun YH5, Seong BL5, Nguyen HH6.
Author information
Abstract
Influenza vaccines aimed at inducing antibody (Ab) responses against viral surface hemagglutinin (HA) and neuraminidase (NA) provide sterile immunity to infection with the same subtypes. Vaccines targeting viral conserved determinants shared by the influenza A viruses (IAV) offer heterosubtypic immunity (HSI), a broad protection against different subtypes. We proposed that vaccines targeting both HA and the conserved ectodomain of matrix protein 2 (M2e) would provide protection against infection with the same subtype and also HSI against other subtypes. Here we report that single intranasal (i.n.) immunization with a recombinant adenovirus (rAd) vector encoding both HA of H5 virus and M2e (rAdH5/M2e) induced significant HA and M2e specific Ab responses along with protection against heterosubtypic challenge in mice. The protection is superior as compared to that induced by rAd vector encoding either HA (rAdH5), or M2e (rAdM2e). While protection against homotypic H5 virus is primarily mediated by virus neutralizing (VN) antibodies (Abs), the cross-protection is associated with Abs directed to conserved stalk HA and M2e that seem to have additive effect. Consistently, adoptive transfer of antisera induced by rAdH5/M2e provided the best protection against heterosubtypic challenge as compared to that provided by antisera derived from mice immunized with rAdH5 or rAdM2e. These results support the development of rAd vectored vaccines encoding both H5 and M2e as universal vaccines against different IAV subtypes.
IMPORTANCE:
Current licensed influenza vaccines provide protection limited to the infection with same virus strains, therefore, the composition of influenza vaccines has to be revised every year. We have developed a new universal influenza vaccine that is highly efficient in induction of long-lasting cross-protection against different influenza virus strains. The cross-protection is associated with high level of vaccine-induced antibodies against conserved stalk domain of influenza virus hemagglutinin and ectodomain of matrix protein. The vaccine could be used to stimulate cross-protective antibodies for prevention and treatment of influenza with immediate effect for individuals who fail to respond to or receive the vaccine in due time. The vaccine offers a new tool to control influenza outbreaks including pandemics.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
24920793
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24920793