A comparative analysis of HIV-specific mucosal/systemic T cell immunity and avidity following rDNA/rFPV and poxvirus-poxvirus prime boost immunisations.

Abstract

In this study we have firstly compared a range of recombinant DNA poxvirus prime-boost immunisation strategies and shown that combined intramuscular (i.m.) 2× DNA-HIV/intranasal (i.n.) 2× FPV-HIV prime-boost immunisation can generate high-level of HIV-specific systemic (spleen) and mucosal (genito-rectal nodes, vaginal tissues and lung tissues) T cell responses and HIV-1 p24 Gag-specific serum IgG1, IgG2a and mucosal IgG, SIgA responses in vaginal secretions in BALB/c mice. Data indicate that following rDNA priming, two rFPV booster immunisations were necessary to generate good antibody and mucosal T cell immunity. This data also revealed that mucosal uptake of recombinant fowl pox (rFPV) was far superior to plasmid DNA. To further evaluate CD8+ T cell immunity, i.m. 2× DNA-HIV/i.n. 1× FPV-HIV immunisation strategy was directly compared with single shot poxvirus/poxvirus, i.n. FPV-HIV/i.m. VV-HIV immunisation. Results indicate that the latter strategy was able to generate strong sustained HIV-specific CD8+ T cells with higher avidity, broader cytokine/chemokine profiles and better protection following influenza-K(d)Gag(197-205) challenge compared to rDNA poxvirus prime-boost strategy. Our findings further substantiate the importance of vector selection/combination, order and route of delivery when designing effective vaccines for HIV-1.

• Authors: Charani Ranasinghe, Fiona Eyers, John Stambas, David B Boyle, Ian A Ramshaw, Alistair J Ramsay
• Journal: Vaccine (Vaccine) Vol. 29 Issue 16 Pg. 3008-20 (Apr 05 2011) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 21352941 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• AIDS Vaccines
• HIV Antibodies
• HIV Core Protein p24
• Interleukin-2
• Vaccines, DNA
• p24 protein, Human Immunodeficiency Virus Type 1
• Interferon-gamma

Topics

• AIDS Vaccines (immunology)
• Administration, Intranasal
• Animals
• CD8-Positive T-Lymphocytes (immunology)
• Female
• Fowlpox virus (immunology)
• HIV Antibodies (blood)
• HIV Core Protein p24 (immunology)
• HIV Infections (prevention & control)
• Immunity, Cellular
• Immunity, Humoral
• Immunity, Mucosal
• Immunization, Secondary
• Injections, Intramuscular
• Interferon-gamma (immunology)
• Interleukin-2 (immunology)
• Mice
• Mice, Inbred BALB C
• Plasmids (immunology)
• Vaccines, DNA (immunology)