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Chimeric LAMP-1/p55Gag DNA vaccination in neonatal period induces anti-HIV cellular and humoral immune response in mice
Presented by PAULA ORDONHEZ RIGATO, Brazil.
Rigato P.O.1, Maciel M.2, Goldoni A.L.1, Fusaro A.E.1, Brito C.A.1, Marques E.T.A.2, August T.2, Duarte A.J.S.1, Sato M.N.1
1Laboratory of Medical Investigation in Dermatology and Immunodeficiencies – 56, School of Medicine, University of São Paulo, São Paulo, Brazil, 2Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, United States
Objective: Early prevention of HIV infection in newborns is necessary due to the high mortality of children infected with the virus. Immunization of adult mice with the chimeric DNA vaccine encoding the lysosome-associated membrane protein 1 (LAMP-1) with the p55 HIV gag gene has been described to enhance specific cellular and humoral responses to HIV Gag and induces long-lasting memory response. Here, we investigate the cellular and humoral effects of the LAMP-1/gag vaccine in newborn mice.
Methods: BALB/c mice adult and newborn mice (7-days old) were intradermally immunized with the chimeric LAMP-1/gag, native gag or only LAMP-1 and boosted 18-20 later. IFN-g spot-forming cells (SFC)were assessed by ELISPOT assay using Gag peptides. Proinflammatory cytokines were determined by flow cytometry and antibodies by ELISA.
Results: The magnitude of IFN-g SFC to immunodominant and other Gag peptides from neonate immunized with LAMP/gag was similar to adult immunized mice. LAMP/gag neonate immunization induced high levels of TNF-a by splenocytes upon immunodominant Gag peptide stimulation (AMQMLKETI65-73) than gag immunization. Furthermore, neonatal immunization with both LAMP/gag or gag (1mg or 5mg) stimulated TNF-a, IFN-g, MCP-1 and IL-6 production at similar level than adult mice. Only LAMP/gag immunization in neonate was able to induce IgG anti-Gag, at lower levels compared to adult immunization. Among IgG subclasses, was mainly IgG1 for LAMP/gag vaccination (1mg) while 5mg dose induced a profile composed by IgG1, IgG2a and IgG2b as detected in adult mice.
Conclusion: The DNA construction using LAMP-1 associated to HIV-1 gag gene is immunogenic in early life vaccination and is able to induce a strong and broad response of IFN-g-producing cells to Gag peptides. The chimeric DNA vaccine LAMP-1/gag could be especially useful in neonatal period, when the immune system is still immature.
Supported by: FAPESP, CNPq, LIM-HC/FMUSP.
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