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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

Overlap of HIV-1-specific CTL responses between blood and gut mucosal compartments.For each of the indicated participants with detected HIV-1-specific CTL responses, a pie chart indicates the fraction of peptide pool responses that were detected in blood only, gut mucosa only, or both compartments. The size of the circle is proportional to the number of peptide pool responses.
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pone-0088621-g006: Overlap of HIV-1-specific CTL responses between blood and gut mucosal compartments.For each of the indicated participants with detected HIV-1-specific CTL responses, a pie chart indicates the fraction of peptide pool responses that were detected in blood only, gut mucosa only, or both compartments. The size of the circle is proportional to the number of peptide pool responses.

Mentions: CTL responses against peptide pools were compared between blood and gut in each responder (Figure 6). One deltoid vaccinee (Subject R) displayed responses to 3 pools in the gut only. The other two deltoid vaccinees (Subjects B and T) each had 3 responses only in the blood, one concordant response in blood and gut, and no responses in gut alone. Three of the inguinal vaccinees (Subjects G, Q, and M) had a predominance of responses in the gut only, and the fourth (Subject F) had responses in the blood only; none had concordant CTL responses in both compartments. Note that because these are measurements with peptide pools, concordance of CTL responses against peptide pools may overestimate concordance of recognized epitopes. Overall, however, these results suggest that deltoid vaccination preferentially induces CTL responses in blood with some concordance in gut mucosa, while inguinal vaccination tends to induce more responses only in the gut mucosal compartment at the time points evaluated.


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)

Overlap of HIV-1-specific CTL responses between blood and gut mucosal compartments.For each of the indicated participants with detected HIV-1-specific CTL responses, a pie chart indicates the fraction of peptide pool responses that were detected in blood only, gut mucosa only, or both compartments. The size of the circle is proportional to the number of peptide pool responses.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0088621-g006: Overlap of HIV-1-specific CTL responses between blood and gut mucosal compartments.For each of the indicated participants with detected HIV-1-specific CTL responses, a pie chart indicates the fraction of peptide pool responses that were detected in blood only, gut mucosa only, or both compartments. The size of the circle is proportional to the number of peptide pool responses.
Mentions: CTL responses against peptide pools were compared between blood and gut in each responder (Figure 6). One deltoid vaccinee (Subject R) displayed responses to 3 pools in the gut only. The other two deltoid vaccinees (Subjects B and T) each had 3 responses only in the blood, one concordant response in blood and gut, and no responses in gut alone. Three of the inguinal vaccinees (Subjects G, Q, and M) had a predominance of responses in the gut only, and the fourth (Subject F) had responses in the blood only; none had concordant CTL responses in both compartments. Note that because these are measurements with peptide pools, concordance of CTL responses against peptide pools may overestimate concordance of recognized epitopes. Overall, however, these results suggest that deltoid vaccination preferentially induces CTL responses in blood with some concordance in gut mucosa, while inguinal vaccination tends to induce more responses only in the gut mucosal compartment at the time points evaluated.

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