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Vaccination against heterologous R5 clade C SHIV: prevention of infection and correlates of protection.

Lakhashe SK, Wang W, Siddappa NB, Hemashettar G, Polacino P, Hu SL, Villinger F, Else JG, Novembre FJ, Yoon JK, Lee SJ, Montefiori DC, Ruprecht RM, Rasmussen RA - PLoS ONE (2011)

Bottom Line: A safe, efficacious vaccine is required to stop the AIDS pandemic.Peak viremia was inversely correlated with both cellular immunity (p<0.001) and cross-nAb titers (p<0.001).These data simultaneously linked cellular as well as humoral immune responses with the degree of protection for the first time.

View Article: PubMed Central - PubMed

Affiliation: Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.

ABSTRACT
A safe, efficacious vaccine is required to stop the AIDS pandemic. Disappointing results from the STEP trial implied a need to include humoral anti-HIV-1 responses, a notion supported by RV144 trial data even though correlates of protection are unknown. We vaccinated rhesus macaques with recombinant simian immunodeficiency virus (SIV) Gag-Pol particles, HIV-1 Tat and trimeric clade C (HIV-C) gp160, which induced cross-neutralizing antibodies (nAbs) and robust cellular immune responses. After five low-dose mucosal challenges with a simian-human immunodeficiency virus (SHIV) that encoded a heterologous R5 HIV-C envelope (22.1% divergence from the gp160 immunogen), 94% of controls became viremic, whereas one third of vaccinees remained virus-free. Upon high-dose SHIV rechallenge, all controls became infected, whereas some vaccinees remained aviremic. Peak viremia was inversely correlated with both cellular immunity (p<0.001) and cross-nAb titers (p<0.001). These data simultaneously linked cellular as well as humoral immune responses with the degree of protection for the first time.

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Related in: MedlinePlus

Cellular immunity at the time of initial low-dose SHIV-1157ipEL-p challenge.(A) The frequency of antigen-specific cells measured by IFN-γ ELISPOT assay. No responses were seen in control Group 3. (B) The frequency of SIV Gag and HIV-1 Tat-specific peripheral blood CD4+ and CD8+ T cells producing intracellular IFN-γ, IL-2 and TNF-α was measured using multiparameter flow cytometry. (C) Proliferation of peripheral blood CD4+ and CD8+ T cells in response to SIV Gag or HIV-1 Tat proteins. *, Mamu A*001-positive RM.
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pone-0022010-g003: Cellular immunity at the time of initial low-dose SHIV-1157ipEL-p challenge.(A) The frequency of antigen-specific cells measured by IFN-γ ELISPOT assay. No responses were seen in control Group 3. (B) The frequency of SIV Gag and HIV-1 Tat-specific peripheral blood CD4+ and CD8+ T cells producing intracellular IFN-γ, IL-2 and TNF-α was measured using multiparameter flow cytometry. (C) Proliferation of peripheral blood CD4+ and CD8+ T cells in response to SIV Gag or HIV-1 Tat proteins. *, Mamu A*001-positive RM.

Mentions: Virus-specific immune responses measured on the day of challenge (two weeks after last vaccination) are shown in Figures 2 and 3. All vaccinees (Groups 1+2) developed high-titer binding antibodies to SIVmac251 Gag, HIV-1 Tat and HIV-C gp120 (Figure 2A). Results of neutralization assays against various R5 SHIV strains, including heterologous SHIV-1157ipEL-p [12], SHIV-1157ipd3N4 [10], SHIV-2873Nip [11] and SHIVSF162P4, a clade B strain [22], are shown in Figure 2B. All 12 vaccinees had nAb responses against the challenge virus, SHIV-1157ipEL-p, by peripheral blood mononuclear cell (PBMC)-based assay.


Vaccination against heterologous R5 clade C SHIV: prevention of infection and correlates of protection.

Lakhashe SK, Wang W, Siddappa NB, Hemashettar G, Polacino P, Hu SL, Villinger F, Else JG, Novembre FJ, Yoon JK, Lee SJ, Montefiori DC, Ruprecht RM, Rasmussen RA - PLoS ONE (2011)

Cellular immunity at the time of initial low-dose SHIV-1157ipEL-p challenge.(A) The frequency of antigen-specific cells measured by IFN-γ ELISPOT assay. No responses were seen in control Group 3. (B) The frequency of SIV Gag and HIV-1 Tat-specific peripheral blood CD4+ and CD8+ T cells producing intracellular IFN-γ, IL-2 and TNF-α was measured using multiparameter flow cytometry. (C) Proliferation of peripheral blood CD4+ and CD8+ T cells in response to SIV Gag or HIV-1 Tat proteins. *, Mamu A*001-positive RM.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3140488&req=5

pone-0022010-g003: Cellular immunity at the time of initial low-dose SHIV-1157ipEL-p challenge.(A) The frequency of antigen-specific cells measured by IFN-γ ELISPOT assay. No responses were seen in control Group 3. (B) The frequency of SIV Gag and HIV-1 Tat-specific peripheral blood CD4+ and CD8+ T cells producing intracellular IFN-γ, IL-2 and TNF-α was measured using multiparameter flow cytometry. (C) Proliferation of peripheral blood CD4+ and CD8+ T cells in response to SIV Gag or HIV-1 Tat proteins. *, Mamu A*001-positive RM.
Mentions: Virus-specific immune responses measured on the day of challenge (two weeks after last vaccination) are shown in Figures 2 and 3. All vaccinees (Groups 1+2) developed high-titer binding antibodies to SIVmac251 Gag, HIV-1 Tat and HIV-C gp120 (Figure 2A). Results of neutralization assays against various R5 SHIV strains, including heterologous SHIV-1157ipEL-p [12], SHIV-1157ipd3N4 [10], SHIV-2873Nip [11] and SHIVSF162P4, a clade B strain [22], are shown in Figure 2B. All 12 vaccinees had nAb responses against the challenge virus, SHIV-1157ipEL-p, by peripheral blood mononuclear cell (PBMC)-based assay.

Bottom Line: A safe, efficacious vaccine is required to stop the AIDS pandemic.Peak viremia was inversely correlated with both cellular immunity (p<0.001) and cross-nAb titers (p<0.001).These data simultaneously linked cellular as well as humoral immune responses with the degree of protection for the first time.

View Article: PubMed Central - PubMed

Affiliation: Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.

ABSTRACT
A safe, efficacious vaccine is required to stop the AIDS pandemic. Disappointing results from the STEP trial implied a need to include humoral anti-HIV-1 responses, a notion supported by RV144 trial data even though correlates of protection are unknown. We vaccinated rhesus macaques with recombinant simian immunodeficiency virus (SIV) Gag-Pol particles, HIV-1 Tat and trimeric clade C (HIV-C) gp160, which induced cross-neutralizing antibodies (nAbs) and robust cellular immune responses. After five low-dose mucosal challenges with a simian-human immunodeficiency virus (SHIV) that encoded a heterologous R5 HIV-C envelope (22.1% divergence from the gp160 immunogen), 94% of controls became viremic, whereas one third of vaccinees remained virus-free. Upon high-dose SHIV rechallenge, all controls became infected, whereas some vaccinees remained aviremic. Peak viremia was inversely correlated with both cellular immunity (p<0.001) and cross-nAb titers (p<0.001). These data simultaneously linked cellular as well as humoral immune responses with the degree of protection for the first time.

Show MeSH
Related in: MedlinePlus