Induction of mucosal and systemic antibody and T-cell responses following prime-boost immunization with novel adjuvanted human immunodeficiency virus-1-vaccine formulations
Open Access
- 15 December 2010
- journal article
- Published by Microbiology Society in Journal of General Virology
- Vol. 92 (1), 128-140
- https://doi.org/10.1099/vir.0.023242-0
Abstract
As sexual transmission of human immunodeficiency virus-1 (HIV-1) occurs via the mucosa, an ideal HIV-1 vaccine should induce both mucosal and systemic immunity. We therefore sought to evaluate the induction of mucosal responses using a DNA env prime–gp120 protein boost approach in which sequential nasal and parenteral protein administration was performed with two novel carbohydrate-based adjuvants. These adjuvants, Advax-M and Advax-P, were specifically designed for mucosal and systemic immune enhancement, respectively. Murine intranasal immunization with gp120/Advax-M adjuvant elicited gp120-specific IgA in serum and mucosal secretions that was markedly enhanced by DNA priming. Boosting of DNA-primed mice with gp120/Advax-M and gp120/Advax-P by sequential intranasal and intramuscular immunization, or vice versa, elicited persistent mucosal gp120-specific IgA, systemic IgG and memory T- and B-cell responses. Induction of homologous, but not heterologous, neutralizing activity was noted in the sera of all immunized groups. While confirmation of efficacy is required in challenge studies using non-human primates, these results suggest that the combination of DNA priming with sequential nasal and parenteral protein boosting, with appropriate mucosal and systemic adjuvants, could generate strong mucosal and systemic immunity and may block HIV-1 mucosal transmission and infection.Keywords
This publication has 88 references indexed in Scilit:
- Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in ThailandNew England Journal of Medicine, 2009
- Discordant memory B cell and circulating anti-Env antibody responses in HIV-1 infectionProceedings of the National Academy of Sciences, 2009
- Effector memory T cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challengeNature Medicine, 2009
- Toll-Like Receptor Signaling in Small Intestinal Epithelium Promotes B-Cell Recruitment and IgA Production in Lamina PropriaGastroenterology, 2008
- The safety and tolerability of an HIV-1 DNA prime–protein boost vaccine (DP6-001) in healthy adult volunteersVaccine, 2008
- Delivery of DNA HIV-1 vaccine to the liver induces high and long-lasting humoral immune responsesVaccine, 2008
- DNA-MVA Vaccine Protection after X4 SHIV Challenge in Macaques Correlates with Day-of-Challenge Antiviral CD4+Cell-Mediated Immunity Levels and Postchallenge Preservation of CD4+T Cell MemoryAIDS Research and Human Retroviruses, 2008
- GM-CSF DNA: An adjuvant for higher avidity IgG, rectal IgA, and increased protection against the acute phase of a SHIV-89.6P challenge by a DNA/MVA immunodeficiency virus vaccineVirology, 2007
- Glycolipid α-C-galactosylceramide is a distinct inducer of dendritic cell function during innate and adaptive immune responses of miceProceedings of the National Academy of Sciences, 2006
- An efficient method to make human monoclonal antibodies from memory B cells: potent neutralization of SARS coronavirusNature Medicine, 2004