科學(xué)家可能發(fā)現(xiàn)了近來(lái)終止的艾滋病疫苗試驗(yàn)中一些參與者在接種疫苗后更容易感染HIV-1病毒的一個(gè)解釋。HIV-1疫苗的STEP臨床試驗(yàn)第II期在2007年停止,，這是由于接種這種疫苗的一些成年人表現(xiàn)出的感染率比對(duì)照組增加。
Steven Patterson及其同事發(fā)現(xiàn)了此前曾經(jīng)接觸過(guò)一種血清型5的腺病毒（一種常見的人類病原體）的人在接種Ad5（本質(zhì)上是這種疫苗的給藥載體）之后變得對(duì)于HIV-1更加脆弱,。這組科學(xué)家提出，當(dāng)此前接觸過(guò)腺病毒的人接種疫苗后,，他們的免疫系統(tǒng)通過(guò)增加黏膜中的CD4 T細(xì)胞從而做出應(yīng)答,。這些CD4 T細(xì)胞是HIV-1的關(guān)鍵靶標(biāo)細(xì)胞，而且為該病毒提供了用于感染和繁殖的更多細(xì)胞,。這組作者說(shuō),，與腺病毒陰性的個(gè)體相比，大量CD4 T細(xì)胞可以增加腺病毒陽(yáng)性個(gè)體被艾滋病病毒感染的機(jī)會(huì),。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
