Mother's Protection

HIV Budding

Antibodies May Prevent Mother-to-Infant Transmission of HIV
July 12, 2015


We often think of HIV as an adult disease, but according to the World Health Organization 240,000 children under 15 were infected with HIV in 2013.

Most of those infections came from the children’s mothers, as children can be exposed to the virus during pregnancy, delivery and breastfeeding. The WHO reports that two thirds of infected pregnant women in low-income countries received antiretroviral drugs to prevent the transmission of HIV to their children.

HIV Infected T-CellFor many women, however, these drugs are not available, either because of high price or low access. But for those women without access to antiretroviral therapy, the body has some surprisingly effective natural defenses. Even without drugs to help, only 25% of infected mothers transmit the virus to their children, according to the CDC.

That is a surprisingly low figure, given the chronic exposure to HIV. Now scientists from the Duke Human Vaccine Institute think they know why, and it may help to prevent even more mother-to-infant transmissions.

According to the researchers, the actors behind the transmission-blocking scene are antibodies produced in the mother’s blood. They looked at a large collection of data from HIV cases in the 1990s and noticed that mothers who did not pass the virus to their children all had a buildup of antibodies attacking a specific piece of the virus’s outer shell.

That piece is called the V3 Loop. The “V” stands for variable, meaning that this section is often built slightly differently from one patient to the next. In fact, the V3 Loop is so changeable, that most researchers have dismissed it as a usable target for possible vaccines, because a vaccine designed to attack it would need to account for the many variations or it would not work for everybody.

It is curious, therefore, that the body attacks this nebulous region of the HIV envelope to such great effect in preventing mother-to-infant transmissions. Dr. Sallie Permar, Duke pediatrician and lead author of the study, hypothesizes that this might be because, to some degree, fetuses have an advantage over vaccine designers in attacking the V3 Loop.

In utero, a fetus is exposed not only to the mother’s virus, but also to her antibodies. While trying to fight off an HIV infection, the mother’s body will create antibodies geared specifically toward fighting the brand of HIV virus she is infected with. That means her immune system will only design antibodies to attack one type of V3 Loop — the one in her body.

Antibody Attacking HIVUnfortunately for the mother, these antibodies cannot cure her HIV, because her immune system is playing catch-up. By the time the immune system recognizes the virus as a threat, designs an antibody to attack it and manufactures that antibody, the infection will have grown to the point where she cannot build enough antibody fast enough to combat it.

The fetus, on the other hand, is exposed to both the virus and the mother’s antibodies specifically designed to fight the virus at the same time. The fetus learns how to make the antibody very early on, and armed with that antibody, it has a good chance of keeping the infection at bay through the pregnancy and beyond.

That said, those children are not immune to HIV later in life. The antibodies they inherited are designed to attack the mother’s virus specifically, but due to the changeability of V3 Loop their antibodies may not recognize HIV from someone else as a threat. This is why Permar thinks the V3 Loop is a good target for preventing mother-to-infant transmissions, but not other types of transmissions.

Most mothers naturally create the antibodies that attack the V3 Loop, which explains why the rate of mother-to-infant transmissions is as low as it is, but there were still 240,000 new cases of HIV in children in 2013. This is because some mothers do not create enough of these antibodies to prevent the infection, if they make them at all.

The good news, according to study co-author Dr. Anthony Moody, is that there are several vaccines currently making their way through clinical trials that are designed to induce several types of antibody reactions, including those to fight the V3 Loop.

Moody says these vaccines may inadvertently be the tool that doctors need to stop all mother-to-infant transmissions. More studies will be needed to see how effective these vaccines are at stopping the spread of HIV from mother to child, and Permar says the Duke Human Vaccine Institute will do studies of other experimental vaccines to see if they can have a similar effect.

A paper describing the research was published in the Journal of Clinical Investigation.

— Daniel Lane

Daniel Lane covers science, engineering, medicine and the environment in North Carolina.


GSK