In August 2024 researchers at Weill Cornell Medicine shared that their strategy to provide protection against HIV has shown promise in a study. The paper in Science Immunology (not open access) explores the potential of a multidose immunisation regimen in infant rhesus macaques. Six vaccinations, containing a modified surface protein, stimulated “initial steps of a potent immune response”. The authors hope that a childhood immunisation approach could provide protection before the risk of contracting HIV “dramatically increases in adolescence”.
HIV in adolescents
HIV “predominantly” infects CD4 T cells, putting individuals at risk of “opportunistic diseases”. Infection can be fatal without lifelong treatment. UNICEF data reveal that adolescents and young people are a “growing share” of people living with HIV. Indeed, in 2023, 140,000 adolescents between the ages of 15 and 19 were newly infected with HIV. If this trend continues, UNICEF estimates that there will be around 183,000 new HIV infections among adolescents in 2030.
Risk factors and immunity
Dr Sallie Permar, Nancy C. Paduano Professor in Paediatrics and Chair of the Department of Paediatrics at Weill Cornell Medicine highlights the logic of immunising children, rather than adults. Not only do risk factors for HIV infection rise “steeply” as adolescents become sexually active, but evidence shows that infants and children are able to mount more effective immune responses to the virus than adults.
“One of the advancements we’ve made is to demonstrate that an HIV vaccine could be delivered on a schedule similar to routine vaccines already given to babies and children.”
An experimental vaccine
Vaccine research is looking for ways to stimulate broadly neutralising antibodies before exposure to the virus. In the latest study, the researchers used an experimental vaccine that had been developed from spike proteins on the envelope of HIV particles. Dr John Moore, professor of microbiology and immunology, and Dr Rogier Sanders, adjunct associate professor of research in microbiology and immunology, set out to “improve” the vaccine by altering the viral protein. The changes targeted a specific set of antibody-producing B cells, which provide protection for CD4 T cells. First author Dr Ashley Nelson, assistant professor of immunology research in paediatrics, commented on the importance of engaging the “right set” of B cells to generate a broadly protective response.
“We discovered that introducing certain mutations into the envelope protein could accomplish that in the setting of a naïve immune system.”
The study
The team administered the modified vaccine to five infant rhesus macaques in three priming doses; the first was administered less than a week after birth. This was followed by three doses of the vaccine matching the original HIV envelope protein. The final dose was given when the animals reached 78 weeks old; this is “roughly” equivalent to four or five years old in humans. Five animals also received all six doses of the original envelope protein vaccine as a control.
Three of the five animals who received the modified vaccine developed antibodies that “appeared to be precursors” to the broadly neutralising response. Investigations revealed that these antibodies attacked the site that the virus uses to invade CD4 T cells. However, they were not “fully effective against the same breadth of HIV strains” as “mature” broadly neutralising antibodies. One animal showed signs of developing this mature response.
Dr Nelson recognised that, although exposure to the modified protein “got the immune response started off in the right direction”, the “full potential” was achieved with booster shots containing the original version.
“We still need to identify the right combination of viral proteins to get us further down that path, starting from the earliest stages in life when multi-dose vaccines are commonly given.”
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