科学家可能发现了近来终止的艾滋病疫苗试验中一些参与者在接种疫苗后更容易感染HIV-1病毒的一个解释。HIV-1疫苗的STEP临床试验第II期在2007年停止，这是由于接种这种疫苗的一些成年人表现出的感染率比对照组增加。
Steven Patterson及其同事发现了此前曾经接触过一种血清型5的腺病毒（一种常见的人类病原体）的人在接种Ad5（本质上是这种疫苗的给药载体）之后变得对于HIV-1更加脆弱。这组科学家提出，当此前接触过腺病毒的人接种疫苗后，他们的免疫系统通过增加黏膜中的CD4 T细胞从而做出应答。这些CD4 T细胞是HIV-1的关键靶标细胞，而且为该病毒提供了用于感染和繁殖的更多细胞。这组作者说，与腺病毒阴性的个体相比，大量CD4 T细胞可以增加腺病毒阳性个体被艾滋病病毒感染的机会。（生物谷Bioon.com）
生物谷推荐原始出处：
PNAS November 16, 2009, doi: 10.1073/pnas.0907898106
Adenovirus vector vaccination induces expansion of memory CD4 T cells with a mucosal homing phenotype that are readily susceptible to HIV-1
Adel Benlahrecha, Julian Harrisb, Andrea Meisera, Timos Papagatsiasa, Julia Horniga, Peter Hayesa, Andre Lieberc, Takis Athanasopoulosb, Veronique Bachyd, Eszter Csomord, Rod Danielse, Kerry Fisherf, Frances Gotcha, Len Seymourf, Karen Logana, Romina Barbagalloa, Linda Klavinskisd, George Dicksonb and Steven Pattersona,1
aDepartment of Immunology, Imperial College London, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, United Kingdom;
bSchool of Biological Science, Royal Holloway University of London, Egham, Surrey TW20 0EX, United Kingdom;
cDivision of Medical Genetics, Department of Medicine, University of Washington, 1705 NE Pacific Street, Seattle, WA 98195;
dPeter Gorer Department of Immunobiology, Guy's Hospital, King's College London, London SE1 9RT, United Kingdom;
eVirology Division, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom; and
fHybrid Systems Ltd., 77 Heyford Park, Upper Heyford OX25 5HD, Oxfordshire, United Kingdom
In the recently halted HIV type 1 (HIV-1) vaccine STEP trial, individuals that were seropositive for adenovirus serotype 5 (Ad5) showed increased rates of HIV-1 infection on vaccination with an Ad5 vaccine. We propose that this was due to activation and expansion of Ad5-specific mucosal-homing memory CD4 T cells. To test this hypothesis, Ad5 and Ad11 antibody titers were measured in 20 healthy volunteers. Dendritic cells (DCs) from these individuals were pulsed with replication defective Ad5 or Ad11 and co-cultured with autologous lymphocytes. Cytokine profiles, proliferative capacity, mucosal migration potential, and susceptibility to HIV infection of the adenovirus-stimulated memory CD4 T cells were measured. Stimulation of T cells from healthy Ad5-seropositive but Ad11-seronegative individuals with Ad5, or serologically distinct Ad11 vectors induced preferential expansion of adenovirus memory CD4 T cells expressing α4β7 integrins and CCR9, indicating a mucosal-homing phenotype. CD4 T-cell proliferation and IFN-γ production in response to Ad stimulation correlated with Ad5 antibody titers. However, Ad5 serostatus did not correlate with total cytokine production upon challenge with Ad5 or Ad11. Expanded Ad5 and Ad11 memory CD4 T cells showed an increase in CCR5 expression and higher susceptibility to infection by R5 tropic HIV-1. This suggests that adenoviral-based vaccination against HIV-1 in individuals with preexisting immunity against Ad5 results in preferential expansion of HIV-susceptible activated CD4 T cells that home to mucosal tissues, increases the number of virus targets, and leads to a higher susceptibility to HIV acquisition.
