Research at Weill Cornell Medicine suggests that childhood immunization against HIV could one day provide protection before the risk of contracting this potentially fatal infection increases dramatically in adolescence.
The study, published Aug. 30 in Science Immunology, showed that a series of six vaccinations containing a modified protein from the surface of HIV particles stimulated the initial steps of a strong immune response in young nonhuman primates. This elusive response represents an important step toward providing complete and potentially lifelong protection against the virus, the researchers say.
Immunizing young children rather than adults makes sense because risk factors for HIV infection skyrocket when adolescents become sexually active, 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.
In addition, evidence shows that the immune systems of infants and children generally respond more effectively to the virus than those of adults. “One of the advances we’ve made is to demonstrate that an HIV vaccine could be delivered in a schedule similar to the routine vaccines already given to babies and children.”
Dr. Sallie Permar, the Nancy C. Paduano Professor of Pediatrics and chair of the Department of Pediatrics at Weill Cornell Medicine
Prepare the immune system in time
HIV mainly infects cells of the immune system called CD4 T cells, leaving people vulnerable to opportunistic diseases. Without lifelong treatment, the infection is fatal. In 2022, an estimated 140,000 adolescents between the ages of 10 and 19 worldwide were infected with the virus – a group that is overrepresented in the number of new 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 critical part of HIV – the protein on its surface that binds to CD4 T cells. In this way, general neutralizing antibodies prevent many strains of HIV from entering the cell and infecting it.
In this study, the researchers started with an experimental vaccine previously developed from spike proteins on the envelope of HIV particles. The authors of the study Dr. John Moore, professor of microbiology and immunology, and Dr. Rogier Sanders, associate research professor of microbiology and immunology at Weill Cornell Medicine and professor at Amsterdam UMC, tried to improve this vaccine by changing the virus. protein. They designed these changes to stimulate a specific set of B cells that produce antibodies that protect CD4 T cells.
“An effective HIV vaccine must engage the correct set of B cells in order to generate a broad protective response,” said first author Dr. Ashley Nelson, assistant professor of immunology research in pediatrics at Weill Cornell Medicine. “We found that introducing certain mutations into the envelope protein could achieve this in the context of a naïve immune system.”
Activating the right B cells for protection
The researchers administered the modified vaccine to five young primates in three booster doses, starting less than a week after birth. They followed three doses of the vaccine that matched the original HIV envelope protein, with the last dose given when the animals reached 78 weeks of age, roughly equivalent to four or five years of age for a human. As a control, five animals received all six doses of the original envelope protein vaccine.
“While exposure to the modified protein got the immune response started in the right direction, booster shots containing the original version of the viral protein were necessary to reach full potential,” said Dr. Nelson.
Three of the five animals that received the modified version of the primer developed antibodies that appeared to be precursors to the sought-after broadly neutralizing response. The tests showed that these antibodies attacked the site the virus uses to invade CD4 T cells. However, they were not yet fully effective against the same range of HIV strains as mature, broadly neutralizing antibodies. One of the three animals also showed signs of developing the mature, broadly neutralizing response.
The next step is to figure out how to reliably induce a complete and broadly neutralizing response, Dr. Nelson said. “We have yet to identify the right combination of viral proteins to take us further down this path, starting at the earliest stages of life, when multiple-dose vaccines are typically given.”
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Journal Reference:
Nelson, AN, et al. (2024) Immunization with germline-targeted SOSIP tripartite induces broadly neutralizing antibody precursors in infant macaques. Science Immunology. doi.org/10.1126/sciimmunol.adm7097.
