Boston – The antibody function known as antibody dependent cellular cytotoxicity (ADCC) is associated with protection against HIV in infants, according to new research from Boston Medical Center. Data from the study show that infants with high levels of ADCC against their mother’s strain of HIV are less likely to get HIV through breast milk and have lower rates of morbidity and death even without antiretroviral therapy. Published in Cell Reports Medicine, the findings demonstrate that ADCC could be a potential new target for future vaccine research.
Researchers evaluated the ADCC present in pre-transmission infant and maternal plasma and breast milk against existing maternal HIV-1 variants. The infants who were exposed yet uninfected had higher ADCC and a combination of ADCC and neutralizing antibody responses against their corresponding mother’s strains, compared to HIV-1 exposed and infected infants. The infected infants with high ADCC function also had lower morbidity and mortality up to one year after birth.
This study shows that ADCC is not correlated with neutralizing antibodies, suggesting these are independent activities, and that ADCC is more effective than neutralizing antibodies in protecting infants against the exposure strains associated with lower mother-to-child transmission and decreases post-infection infant morbidity.
“HIV vaccine efforts have been primarily focused on eliciting neutralizing antibodies,” says Manish Sagar, an infectious diseases physician at Boston Medical Center and corresponding author on this study. “The results of this study suggest that there are additional immune factors that may be associated with protection against HIV transmission.”
Each year, 50,000 infants are infected with HIV primarily through mother to child transmission. Improving outcomes in the infants that become infected is important, especially because of limited access to antiretroviral therapy. The findings of this study support the argument that vaccine efforts should also focus on enhancing ADCC responses among the highly exposed at-risk individuals. This is especially relevant because current immunogens have been unable to elicit neutralizing antibodies, so inducing ADCC responses may be more feasible target.
Without antiretroviral treatment, the risk of transmission during the breastfeeding period is between 10 and 20 percent depending on duration of breastfeeding, which suggests natural immune mechanisms that protect against HIV acquisition. Infants acquire HIV at a lower frequency than typically expected, considering the long duration of viral exposure in-utero and during breastfeeding. Infants passively acquire maternal antibodies before and while they are consistently exposed to the virus.
Samples of patient breast milk and maternal plasma were examined from mother-infant pairs that were enrolled from a previous mother-to-child-transmission clinical trial in Malawi. All mothers had chronic HIV infection and had breastfed their babies, who did not have HIV at the start of the study. The antibody functions were compared among the 16 mothers that did transmit HIV to the 26 that did not, and among infants that did eventually acquire HIV from their mother with those that did not. The ADCC that was present in pre-transmission infant and maternal plasma and breast milk was compared against the existing maternal HIV-1 variants.
“Similar to COVID-19, it is generally believed that if people have pre-existing neutralizing antibodies against HIV, it will protect them from acquiring HIV,” says Sagar, also an associate professor of medicine and microbiology at Boston University School of Medicine. “Unlike COVID-19, however, this research demonstrates that the presence of neutralizing antibodies in exposed individuals does not protect from HIV transmission.”
Researchers recommend additional research efforts should be dedicated to understanding ADCC and enhancing ADCC with future vaccine products, while aiming to elicit robust ADCC activity to prevent mother-to-child transmission and to improve infant outcomes.
Funding for the study was supported by NIH grant R21-AI137119, K24-AI145661, P30- AI042853, and by NIH T32-5T32AI00730928.
About Boston Medical Center
Boston Medical Center (BMC) is a private, not-for-profit, 514-bed, academic medical center that is the primary teaching affiliate of Boston University School of Medicine. It is the largest and busiest provider of trauma and emergency services in New England. BMC offers specialized care for complex health problems and is a leading research institution, receiving more than $166 million in sponsored research funding in fiscal year 2019. It is the 13th largest funding recipient in the U.S. from the National Institutes of Health among independent hospitals. In 1997, BMC founded Boston Medical Center Health Plan, Inc., now one of the top ranked Medicaid MCOs in the country, as a non-profit managed care organization. Boston Medical Center and Boston University School of Medicine are partners in Boston HealthNet – 12 community health centers focused on providing exceptional health care to residents of Boston. For more information, please visit http://www.bmc.org.
Cell Reports Medicine
Pre-existing infant antibody-dependent cellular cytotoxicity associates with reduced HIV-1 acquisition and lower morbidity
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