tetano
Editor, Senior Moderator
Vaccine. 2010 Nov 24. [Epub ahead of print]
Alphavirus replicon-based adjuvants enhance the immunogenicity and effectiveness of Fluzone(?) in rhesus macaques.
Carroll TD, Matzinger SR, Barro M, Fritts L, McChesney MB, Miller CJ, Johnston RE.
Center for Comparative Medicine, University of California-Davis, One Shields Avenue, Davis, CA 95616, USA; California National Primate Research Center, University of California-Davis, One Shields Avenue, Davis, CA 95616, USA.
Abstract
Venezuelan equine encephalitis virus replicon particles (VRP) without a transgene (null VRP) have been used to adjuvant effective humoral [1], cellular [2], and mucosal [3] immune responses in mice. To assess the adjuvant activity of null VRP in the context of a licensed inactivated influenza virus vaccine, rhesus monkeys were immunized with Fluzone(?) alone or Fluzone(?) mixed with null VRP and then challenged with a human seasonal influenza isolate, A/Memphis/7/2001 (H1N1). Compared to Fluzone(?) alone, Fluzone(?)+null VRP immunized animals had stronger influenza-specific CD4(+) T cell responses (4.4 fold) with significantly higher levels of virus-specific IFN-γ (7.6 fold) and IL-2 (5.3 fold) producing CD4+ T cells. Fluzone(?)+null VRP immunized animals also had significantly higher plasma anti-influenza IgG (p<0.0001, 1.3 log) and IgA (p<0.05, 1.2 log) levels. In fact, the mean plasma anti-influenza IgG titers after one Fluzone(?)+null VRP immunization was 1.2 log greater (p<0.04) than after two immunizations with Fluzone(?) alone. After virus challenge, only Fluzone(?)+null VRP immunized monkeys had a significantly lower level of viral replication (p<0.001) relative to the unimmunized control animals. Although little anti-influenza antibody was detected in the respiratory secretions after immunization, strong anamnestic anti-influenza IgG and IgA responses were present in secretions of the Fluzone(?)+null VRP immunized monkeys immediately after challenge. There were significant inverse correlations between influenza RNA levels in tracheal lavages and plasma anti-influenza HI and IgG anti-influenza antibody titers prior to challenge. These results demonstrate that null VRP dramatically improve both the immunogenicity and protection elicited by a licensed inactivated influenza vaccine.
Copyright ? 2010. Published by Elsevier Ltd.
PMID: 21111777 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21111777
Alphavirus replicon-based adjuvants enhance the immunogenicity and effectiveness of Fluzone(?) in rhesus macaques.
Carroll TD, Matzinger SR, Barro M, Fritts L, McChesney MB, Miller CJ, Johnston RE.
Center for Comparative Medicine, University of California-Davis, One Shields Avenue, Davis, CA 95616, USA; California National Primate Research Center, University of California-Davis, One Shields Avenue, Davis, CA 95616, USA.
Abstract
Venezuelan equine encephalitis virus replicon particles (VRP) without a transgene (null VRP) have been used to adjuvant effective humoral [1], cellular [2], and mucosal [3] immune responses in mice. To assess the adjuvant activity of null VRP in the context of a licensed inactivated influenza virus vaccine, rhesus monkeys were immunized with Fluzone(?) alone or Fluzone(?) mixed with null VRP and then challenged with a human seasonal influenza isolate, A/Memphis/7/2001 (H1N1). Compared to Fluzone(?) alone, Fluzone(?)+null VRP immunized animals had stronger influenza-specific CD4(+) T cell responses (4.4 fold) with significantly higher levels of virus-specific IFN-γ (7.6 fold) and IL-2 (5.3 fold) producing CD4+ T cells. Fluzone(?)+null VRP immunized animals also had significantly higher plasma anti-influenza IgG (p<0.0001, 1.3 log) and IgA (p<0.05, 1.2 log) levels. In fact, the mean plasma anti-influenza IgG titers after one Fluzone(?)+null VRP immunization was 1.2 log greater (p<0.04) than after two immunizations with Fluzone(?) alone. After virus challenge, only Fluzone(?)+null VRP immunized monkeys had a significantly lower level of viral replication (p<0.001) relative to the unimmunized control animals. Although little anti-influenza antibody was detected in the respiratory secretions after immunization, strong anamnestic anti-influenza IgG and IgA responses were present in secretions of the Fluzone(?)+null VRP immunized monkeys immediately after challenge. There were significant inverse correlations between influenza RNA levels in tracheal lavages and plasma anti-influenza HI and IgG anti-influenza antibody titers prior to challenge. These results demonstrate that null VRP dramatically improve both the immunogenicity and protection elicited by a licensed inactivated influenza vaccine.
Copyright ? 2010. Published by Elsevier Ltd.
PMID: 21111777 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21111777