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Differential blood and mucosal immune responses against an HIV-1 vaccine administered via inguinal or deltoid injection.

Yang OO, Ibarrondo FJ, Price C, Hultin LE, Elliott J, Hultin PM, Shih R, Hausner MA, Ng HL, Hoffman J, Jamieson BD, Anton PA - PLoS ONE (2014)

Bottom Line: HIV-1-specific CD8(+) T lymphocytes (CTLs) were observed in 7/12 vaccinees, and blood and gut targeting were distinct.Within blood, both deltoid and inguinal responders had detectable CTL responses by 17-24 days; inguinal responders had early responses (within 10 days) while deltoid responders had later responses (24-180 days) in gut mucosa.Our results demonstrate relative safety of inguinal vaccination and qualitative or quantitative compartmentalization of immune responses between blood and gut mucosa, and highlight the importance of not only evaluating early blood responses to HIV-1 vaccines but also mucosal responses over time.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine and University of California Los Angeles AIDS Institute, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America ; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America ; AIDS Healthcare Foundation, Los Angeles, California, United States of America.

ABSTRACT

Unlabelled: Mucosal immunity is central to sexual transmission and overall pathogenesis of HIV-1 infection, but the ability of vaccines to induce immune responses in mucosal tissue compartments is poorly defined. Because macaque vaccine studies suggest that inguinal (versus limb) vaccination may better target sexually-exposed mucosa, we performed a randomized, double-blinded, placebo-controlled Phase I trial in HIV-1-uninfected volunteers, using the recombinant Canarypox (CP) vaccine vCP205 delivered by different routes. 12 persons received vaccine and 6 received placebo, divided evenly between deltoid-intramuscular (deltoid-IM) or inguinal-subcutaneous (inguinal-SC) injection routes. The most significant safety events were injection site reactions (Grade 3) in one inguinal vaccinee. CP-specific antibodies were detected in the blood of all 12 vaccinees by Day 24, while HIV-1-specific antibodies were observed in the blood and gut mucosa of 1/9 and 4/9 evaluated vaccinees respectively, with gut antibodies appearing earlier in inguinal vaccinees (24-180 versus 180-365 days). HIV-1-specific CD8(+) T lymphocytes (CTLs) were observed in 7/12 vaccinees, and blood and gut targeting were distinct. Within blood, both deltoid and inguinal responders had detectable CTL responses by 17-24 days; inguinal responders had early responses (within 10 days) while deltoid responders had later responses (24-180 days) in gut mucosa. Our results demonstrate relative safety of inguinal vaccination and qualitative or quantitative compartmentalization of immune responses between blood and gut mucosa, and highlight the importance of not only evaluating early blood responses to HIV-1 vaccines but also mucosal responses over time.

Trial registration: ClinicalTrials.gov NCT00076817.

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Related in: MedlinePlus

Total observed CTL responses against HIV-1 in blood and gut mucosal compartments.The background-subtracted CTL responses of all participants against HIV-1 vaccine peptide pools were summed for persons who received placebo (circles) and vCP205 vaccinations (squares) and plotted for blood (left) and gut mucosa (right). p-values indicate significant differences between groups by Students t-test.
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pone-0088621-g003: Total observed CTL responses against HIV-1 in blood and gut mucosal compartments.The background-subtracted CTL responses of all participants against HIV-1 vaccine peptide pools were summed for persons who received placebo (circles) and vCP205 vaccinations (squares) and plotted for blood (left) and gut mucosa (right). p-values indicate significant differences between groups by Students t-test.

Mentions: The two vaccination groups were compared for CTL responses in both blood and gut mucosa. On Days 0, 10, 17, 24, 180, and 365 after the first vaccination, HIV-1-specific CTL responses were assessed in both compartments by IFN-γ ELISpot assay for reactivity against the HIV-1 protein sequences expressed by vCP205. Baseline responses before treatment were established for each subject in both compartments. The mean of the baseline background-subtracted responses was −5.51 (95% CI −7.42 to −3.62) spot-forming cells per million CD8+ T lymphocytes, with a false positive rate of 1.5%. In blood (Figure 3a), there was a significant increase in HIV-1-reactivity (p = 0.004) by Day 24. For gut (Figure 3b), the response was borderline significant on Day 180 (p = 0.052) and significant on Day 365 (p<0.001).


Differential blood and mucosal immune responses against an HIV-1 vaccine administered via inguinal or deltoid injection.

Yang OO, Ibarrondo FJ, Price C, Hultin LE, Elliott J, Hultin PM, Shih R, Hausner MA, Ng HL, Hoffman J, Jamieson BD, Anton PA - PLoS ONE (2014)

Total observed CTL responses against HIV-1 in blood and gut mucosal compartments.The background-subtracted CTL responses of all participants against HIV-1 vaccine peptide pools were summed for persons who received placebo (circles) and vCP205 vaccinations (squares) and plotted for blood (left) and gut mucosa (right). p-values indicate significant differences between groups by Students t-test.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3928250&req=5

pone-0088621-g003: Total observed CTL responses against HIV-1 in blood and gut mucosal compartments.The background-subtracted CTL responses of all participants against HIV-1 vaccine peptide pools were summed for persons who received placebo (circles) and vCP205 vaccinations (squares) and plotted for blood (left) and gut mucosa (right). p-values indicate significant differences between groups by Students t-test.
Mentions: The two vaccination groups were compared for CTL responses in both blood and gut mucosa. On Days 0, 10, 17, 24, 180, and 365 after the first vaccination, HIV-1-specific CTL responses were assessed in both compartments by IFN-γ ELISpot assay for reactivity against the HIV-1 protein sequences expressed by vCP205. Baseline responses before treatment were established for each subject in both compartments. The mean of the baseline background-subtracted responses was −5.51 (95% CI −7.42 to −3.62) spot-forming cells per million CD8+ T lymphocytes, with a false positive rate of 1.5%. In blood (Figure 3a), there was a significant increase in HIV-1-reactivity (p = 0.004) by Day 24. For gut (Figure 3b), the response was borderline significant on Day 180 (p = 0.052) and significant on Day 365 (p<0.001).

Bottom Line: HIV-1-specific CD8(+) T lymphocytes (CTLs) were observed in 7/12 vaccinees, and blood and gut targeting were distinct.Within blood, both deltoid and inguinal responders had detectable CTL responses by 17-24 days; inguinal responders had early responses (within 10 days) while deltoid responders had later responses (24-180 days) in gut mucosa.Our results demonstrate relative safety of inguinal vaccination and qualitative or quantitative compartmentalization of immune responses between blood and gut mucosa, and highlight the importance of not only evaluating early blood responses to HIV-1 vaccines but also mucosal responses over time.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine and University of California Los Angeles AIDS Institute, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America ; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America ; AIDS Healthcare Foundation, Los Angeles, California, United States of America.

ABSTRACT

Unlabelled: Mucosal immunity is central to sexual transmission and overall pathogenesis of HIV-1 infection, but the ability of vaccines to induce immune responses in mucosal tissue compartments is poorly defined. Because macaque vaccine studies suggest that inguinal (versus limb) vaccination may better target sexually-exposed mucosa, we performed a randomized, double-blinded, placebo-controlled Phase I trial in HIV-1-uninfected volunteers, using the recombinant Canarypox (CP) vaccine vCP205 delivered by different routes. 12 persons received vaccine and 6 received placebo, divided evenly between deltoid-intramuscular (deltoid-IM) or inguinal-subcutaneous (inguinal-SC) injection routes. The most significant safety events were injection site reactions (Grade 3) in one inguinal vaccinee. CP-specific antibodies were detected in the blood of all 12 vaccinees by Day 24, while HIV-1-specific antibodies were observed in the blood and gut mucosa of 1/9 and 4/9 evaluated vaccinees respectively, with gut antibodies appearing earlier in inguinal vaccinees (24-180 versus 180-365 days). HIV-1-specific CD8(+) T lymphocytes (CTLs) were observed in 7/12 vaccinees, and blood and gut targeting were distinct. Within blood, both deltoid and inguinal responders had detectable CTL responses by 17-24 days; inguinal responders had early responses (within 10 days) while deltoid responders had later responses (24-180 days) in gut mucosa. Our results demonstrate relative safety of inguinal vaccination and qualitative or quantitative compartmentalization of immune responses between blood and gut mucosa, and highlight the importance of not only evaluating early blood responses to HIV-1 vaccines but also mucosal responses over time.

Trial registration: ClinicalTrials.gov NCT00076817.

Show MeSH
Related in: MedlinePlus