Unprotected sex with regular partner may provoke an immune response that can protect against HIV

Michael Carter
Published: 19 February 2004

Unprotected sex between monogamous heterosexual partners causes an immune response that may be able to inhibit infection with HIV, according to a laboratory study published in the February 14th edition of The Lancet. The investigators, from Guy’s, King’s and St Thomas’s hospitals in south London, believe that their findings could have important implications for future HIV vaccine research, but are emphasising that their findings do not suggest that individuals should have lots of unprotected sex as a way of protecting themselves against infection with HIV.

Proteins in both male ejaculate and female vaginal secretions, called HLA antigens, are known to cause a potentially powerful alloimmune response, similar to that which causes the body to reject transplanted organs as "foreign".

Studies conducted in monkeys suggested that exposing vaginal or rectal mucosa to the peripheral blood mononuclear cells (PBMC) of another monkey caused an immune reaction, including a decrease in SIV infection of CD4 cells. Laboratory studies have also shown that alloimmunisation leads to a reduction in the number of CCR5 and CXCR4 coreceptors, key entry routes for infection with HIV. Epidemiological evidence from Kenyan sex workers who remained uninfected with HIV despite repeated exposure to the virus also supports the theory that mucosal alloimmunisation confers a degree of resistance to HIV infection.

The south London investigators tested the hypothesis that alloimmunisation is a potential strategy for inducing immune protection against HIV in two groups of heterosexuals. Group one was composed of 29 monogamous couples who had had unprotected vaginal sex for at least six months, and group two included 15 women and ten men who had either had only protected sex for at least six months, or had had no sex for a similar period.

Lead investigator Dr Barry Peters told aidsmap, "We postulated that regular unprotected sex with a partner would involve constant exposure to that person's HLA antigens, and that this would lead to the development of a broad alloimmune response that would recognise HIV as foreign and cause the body to resist cells becoming infected with HIV." HIV carries HLA proteins from the infected host cell on its surface, and so the theory is that an alloimmunisation strategy would allow the vaccinated person to mount a more effective immune response.

This research strategy also has other influential backers. Writing in the September 16th edition of the Proceedings of the National Academy of Sciences, Prof Stephen J Gould concluded, "alloimmunisation is a vaccination strategy that should be used in the fight against HIV."

Blood samples were obtained from individuals and one partner’s PBMC was stimulated using the other’s irradiated (killed) PBMC at three different strengths, low (2%), medium (10%) and high (50%). Resistance to HIV infection was then examined by exposing activated CD4 T-cells to CCR5-binding and CXCR4-binding HIV strains. The infectivity of partners having unprotected sex was then compared to those individuals who either had protected sex or no sex.

A significant increase in immune stimulation indices was noted in the PBMC of women having unprotected sex when exposed to the irradiated PBMC of their partners (at medium strength p=0.009). Significant alloimmune responses were also seen in the corresponding male partners, but only with 50% stimulating cells (p=0.013).

In the laboratory, the investigators then exposed the activated CD4-positive T-cells of women having unprotected sex to binding strains of HIV. They noted that vulnerability to infection with both the CCR5-binding strain (p=0.001) and the CXCR4-binding strain (p=0.001) was significantly inhibited at four different levels of HIV concentration. Laboratory tests also showed that the infectivity of HIV was inhibited in the male partners of women having unprotected sex, but to a lesser degree (p=0.02).

"Our findings suggest that HLA antigens in seminal fluid and vaginal secretions might induce mucosal alloimmunisation in women, and to a lesser extent in men, during unprotected sex," comment the investigators. They add, "our results show that stimulation of T-cell proliferation…was greatly increased in PBMC from women practicing unprotected intercourse in response to their partners’ PBMC than to unrelated control cells (p=0.0001)."

The investigators believe that the exposure of the vaginal mucosa to HLA antigens in seminal fluid led to alloimmunisation in women having unprotected sex.

"Evidence that mucosal alloimmunisation occurs naturally during sexual intercourse indicates a physiological function of enhancing genital immunity to sexually transmitted pathogens and supports the concept of alloimmunisation as a strategy for vaccination against HIV-1 infection," conclude the investigators.

Dr Peters is cautious about these findings, but told aidsmap that it was important to open new fronts in the search for an HIV vaccine, given the disappointing results from trials so far. He also emphasised that his research should not be seen as a reason to have unprotected sex.

Further information on this website


Peters B et al. Effect of heterosexual intercourse on mucosal alloimmunisation and resistance to HIV-1 infection. The Lancet 363: 518 – 524, 2004.

Gould SJ et al. The Trojan exosome hypothesis. PNAS 100: 10592 - 97, 2003.

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