Yang Otto O, Ibarrondo F Javier, Price Charles, Hultin Lance E, Elliott Julie, Hultin Patricia M, Shih Roger, Hausner Mary Ann, Ng Hwee L, Hoffman Jennifer, Jamieson Beth D, Anton Peter A
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.
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.
PLoS One. 2014 Feb 18;9(2):e88621. doi: 10.1371/journal.pone.0088621. eCollection 2014.
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.
ClinicalTrials.gov NCT00076817.
黏膜免疫是HIV-1感染性传播及整体发病机制的核心，但疫苗在黏膜组织区室诱导免疫反应的能力尚不明确。由于猕猴疫苗研究表明腹股沟（相对于肢体）接种可能更好地针对性暴露黏膜，我们在未感染HIV-1的志愿者中进行了一项随机、双盲、安慰剂对照的I期试验，使用通过不同途径递送的重组金丝雀痘病毒（CP）疫苗vCP205。12人接种疫苗，6人接受安慰剂，在三角肌肌内注射（三角肌-IM）或腹股沟皮下注射（腹股沟-SC）途径之间平均分配。最显著的安全事件是一名腹股沟疫苗接种者出现注射部位反应（3级）。到第24天时，在所有12名疫苗接种者的血液中均检测到CP特异性抗体，而在分别评估的9名疫苗接种者中，有1/9和4/9的血液及肠道黏膜中观察到HIV-1特异性抗体，腹股沟疫苗接种者的肠道抗体出现得更早（24 - 180天与180 - 365天）。在12名疫苗接种者中有7人观察到HIV-1特异性CD8(+) T淋巴细胞（CTL），血液和肠道靶向不同。在血液中，三角肌和腹股沟反应者在17 - 24天时均有可检测到的CTL反应；腹股沟反应者在肠道黏膜中有早期反应（10天内），而三角肌反应者在肠道黏膜中的反应较晚（24 - 180天）。我们的结果证明了腹股沟接种的相对安全性以及血液和肠道黏膜之间免疫反应的定性或定量区室化，并强调了不仅要评估对HIV-1疫苗的早期血液反应，还要评估随时间的黏膜反应的重要性。
ClinicalTrials.gov NCT00076817。
