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Studying broadly neutralizing antibodies in infants may lead to new pathways in HIV vaccine development.
A new article in Cell that studied HIV-neutralizing antibodies in an infant may have important implications in the development of an HIV vaccine. The novel study, published on June 23, 2016, examined broadly neutralizing antibodies (bnAbs) in a Nairobi infant prior to receiving antiretrovirals and approximately one-year post infection. Researchers isolated and characterized infant HIV-1 neutralizing antibodies in order to further understand their impact on the HIV virus.
Multiple studies have been done on HIV-1 bnAbs in adults, but little is known about infant bnAbs contributing to broad plasma responses. While a subset of adults with HIV-1 develop bnAbs, these antibodies exhibit high levels of somatic hypermutation (SHM) and only neutralize the disease after years of affinity maturation. By comparison, infant’s bnAbs develop broad responses early, and “HIV-1-specific neutralization breadth can develop without prolonged affinity maturation and extensive SHM.” Therefore, infants may have the ability to neutralize the disease more quickly than adults.
“Most studies of adults have looked at responses many years after infection and these have suggested that broad and potent HIV neutralizing antibodies take years to develop and that they require extensive hypermutation to be effective,” study author Julie Overbaugh, PhD, member of the Human Biology Division at the Fred Hutchinson Cancer Research Center, told Pharmaceutical Technology. “This is the first example of broadly neutralizing antibodies detected this early in infection. These infant antibodies have much less hypermutation and yet, they are nonetheless broad and potent.”
Overbaugh notes the infant studied had a polyclonal response to the virus, meaning, the infant’s antibodies targeted multiple epitopes, making it more difficult for the virus to survive. This presents an interesting comparison to studies done on adult antibodies, which target only one dominant epitope, Overbaugh says.
The challenge is now finding ways to harness these unique attributes of infant bnAbs for practical applications such as vaccine development. The goal, researchers say, is to better understand infant bnAbs that develop early in natural infection in order to develop vaccines that can elicit neutralizing antibodies more quickly.
“Infants mount a more rapid potent antibody response to HIV than adults-understanding how they do this is important, both in terms of how they do it more rapidly and whether there are fundamental differences in the pathway,” said Overbaugh. “Adults take a long time to develop these responses [naturally], longer than is possible to imagine for a vaccine regimen.”
Defining the pathway that leads to these innate responses will be the focus of future investigation, says Overbaugh. This will involve studying the infant over time and noting how the virus-antibody dynamic shapes the process. This also includes studying the infant’s mother, in order to determine whether passively-acquired maternal antibodies have impacted this response. Overall, Overbaugh notes, studying these pathways in infants may provide a “better template for vaccine design.”