Learning from Mom: how decades-old samples from pregnant mothers can bring us closer to an HIV vaccine
The year is 1997, and a woman at a prenatal clinic in Nairobi has just learned she’s HIV positive. It’s the height of the HIV epidemic and there are more than a million people in Kenya alone that have been infected with HIV. Antiretroviral drugs are not yet widely available. Nurses inform her that she is eligible to enroll in a study of HIV positive pregnant women, would she be willing to take part? It involves pelvic exams, collecting samples from her blood and breastmilk, and monitoring her baby for HIV infection over a period of 2 years after birth. Findings from this study will likely never directly improve her life, as the prognosis is not good for HIV positive individuals in Africa without access to antiretroviral therapy.
And yet she did volunteer. After giving birth, she allowed doctors to take blood samples from the umbilical cord and from her baby, and dutifully returned every three months to continue to undergo HIV testing and breastmilk collection. These samples were frozen in Nairobi, carefully shipped on dry ice to Seattle, where they were placed into a dark building with rows of freezers quietly humming away. And there they have rested for over two decades.
They have not sat undisturbed, however. Scientists like me have occasionally plucked a sample from its frozen slumber, carefully and gently woken the cells and molecules suspended in blood, and performed experiments to understand how each woman’s immune system responded to infection with HIV. These samples contain the answer to a puzzling mystery: why do some babies get infected, and others don’t? HIV infected mothers will give their virus to their baby about 1/3 of the time – when you think about it, that’s less often than you’d expect. Babies share a circulatory system with their mom for 9 months, during the messy process of birth they are exposed to many fluids from their mother, and then babies are breastfed for months afterwards. HIV can be transmitted from mom to baby during any of those stages, and yet only 1/3 of babies will become infected. Why?
It’s probably because babies receive a gift from their mom: antibodies. Antibodies are proteins made by the immune system to defend us from infection. Before we leave the womb, our mothers give us antibodies in order to protect us during the first few months of life. This means that when a baby comes into contact with HIV, it will already have antibodies swirling around, ready to spring into action.
Turns out, if you’re looking for a situation which mimics vaccination, this is pretty close. Because it would be unethical to try out different vaccines on people and purposefully expose them to HIV, instead we can study HIV-exposed babies and try to figure out what was special about the antibodies from infants that stayed uninfected. These special antibodies can hopefully provide us a roadmap for how to build a successful HIV vaccine.
The original Nairobi Breastfeeding Clinical trial ran from 1992 to 1998, but we are still gaining insights from the samples collected back then. These samples are precious because they were taken before antiretroviral therapy was the standard of care, allowing us to observe the protective effect of antibodies without any interference. Cohorts like this will never exist again.
Perhaps the key to an effective HIV vaccine lies in wait amongst the cold and quiet rows of freezers, perhaps in a vial of blood taken from that mother in Kenya many years ago.
Meghan Garrett is a PhD student in the Molecular and Cellular Biology program at UW. She studies the immune response against HIV in infected mothers in order to better understand antibodies that might have protected their infants from infection, with the goal of using this knowledge to improve HIV vaccine design.