Novel study highlights potential of HIV vaccination in children

Research from Weill Cornell Medicine suggests that vaccinating children against HIV could one day provide protection before their risk of contracting the potentially deadly infection increases dramatically during adolescence.

The study, published Aug. 30 in Science Immunology, found that a series of six vaccinations containing a modified protein from the surface of HIV particles stimulated the initial stages of a powerful immune response in newborn nonhuman primates. This difficult-to-achieve response is an essential step toward providing full and potentially lifelong protection against the virus, the researchers said.

Vaccinating newborn children, rather than adults, makes sense because risk factors for HIV infection boost dramatically when teens become sexually vigorous, according to senior author Dr. Sallie Permar, the Nancy C. Paduano Professor of Pediatrics and chair of the Department of Pediatrics at Weill Cornell Medicine.

“Moreover, evidence suggests that the immune systems of infants and children are generally able to respond more effectively to the virus than the immune systems of adults. One of the advances we have made is showing that the HIV vaccine can be given on a schedule similar to the routine vaccines given to infants and children.”

Dr. Sallie Permar, Nancy C. Paduano Professor of Pediatrics and Chair of the Department of Pediatrics at Weill Cornell Medicine

Early preparation of the immune system

HIV primarily infects immune cells called CD4 T cells, making individuals susceptible to opportunistic infections. Without lifelong treatment, the infection is fatal. In 2022, an estimated 140,000 adolescents aged 10 to 19 were infected with the virus worldwide — a group that is overrepresented in the number of novel infections.

Vaccine researchers are looking for ways to stimulate the immune system to produce “broadly neutralizing antibodies” against the virus before a person is exposed to it. These antibodies attack a key part of the HIV virus—a protein on its surface that binds to CD4 T cells. In this way, broadly neutralizing antibodies prevent many strains of HIV from entering and infecting a cell.

In this study, researchers started with an experimental vaccine previously developed from the spike proteins on the HIV particle’s envelope. Study authors John Moore, PhD, professor of microbiology and immunology, and Rogier Sanders, PhD, assistant professor of research in microbiology and immunology at Weill Cornell Medicine and professor at Amsterdam UMC, sought to improve that vaccine by changing the viral protein. They designed those changes to stimulate a specific set of antibody-producing B cells that protect CD4 T cells.

“An effective HIV vaccine must recruit the right set of B cells to generate a broadly protective response,” said first author Ashley Nelson, PhD, assistant professor of pediatric immunology research at Weill Cornell Medicine. “We found that introducing certain mutations into the envelope protein can achieve this in a naive immune system.”

Activation of appropriate B cells to provide protection

The researchers gave the modified vaccine to five newborn primates in three initial doses, starting less than a week after birth. They then gave three doses of the original HIV envelope protein vaccine, and the final dose was given when the animals were 78 weeks elderly, roughly equivalent to four or five years in humans. As controls, five animals received all six doses of the original envelope protein vaccine.

“While exposure to the modified protein kick-started the immune response in the right direction, booster doses containing the original version of the viral protein were necessary to reach full potential,” Dr. Nelson said.

Three of the five animals that received the modified version of the priming vaccine produced antibodies that appeared to be precursors of the desired broadly neutralizing response. Tests suggested that these antibodies attacked the site that the virus uses to invade CD4 T cells. However, they were not yet fully effective against the same breadth of HIV strains as the mature broadly neutralizing antibodies. One of the three animals also showed signs of developing a mature, broadly neutralizing response.

The next step is figuring out how to reliably elicit a full, broadly neutralizing response, Dr. Nelson said. “We still need to identify the right combination of viral proteins to continue down that path, starting early in life when multidose vaccines are commonly administered.”