Weill Cornell Medicine Receives $20.8 Million NIH Grant to Develop Childhood HIV Vaccine
核心洞察
Weill Cornell Medicine investigators have been awarded a five-year, $20.8 million NIH grant to advance preclinical development of an experimental HIV (搜索) vaccine designed for childhood administration.
The vaccine is based on the BG505 GT1.1 SOSIP trimer (搜索) structure and aims to elicit broadly neutralizing antibodies that can protect against multiple HIV (搜索) strains.
Initial studies suggest the vaccine may only be effective when administered to young immune systems, making childhood vaccination the optimal strategy.
A multi-institutional team led by Weill Cornell Medicine investigators has been awarded a five-year, $20.8 million grant from the National Institute of Allergy and Infectious Diseases to advance preclinical development of a promising experimental HIV (搜索) vaccine designed for childhood administration.
The grant represents a significant investment in HIV (搜索) prevention research at a time when approximately 1.3 million people acquired HIV in 2024, according to the World Health Organization, with an estimated 41 million people living with the virus globally. While current medications can keep individuals healthy, they must be taken for a lifetime, making prevention through vaccination a critical public health priority.
Novel Approach Targets Young Immune Systems
The experimental vaccine takes an unconventional approach by targeting childhood immunization rather than following the traditional path of testing in adults first. Prior studies suggest the vaccine is safe and may be effective when administered early in life, with initial clinical trials in adults and preclinical work in rhesus macaque models indicating that the vaccine can elicit useful quantities of broadly neutralizing antibodies (bnAbs) only in young immune systems.
"The ability to induce effective immunity, in childhood, against a broad set of HIV (搜索) variants could revolutionize HIV prevention efforts and ultimately bring this decades-long pandemic to an end," said lead investigator Dr. Sallie Permar, chair of the Department of Pediatrics and the Nancy C. Paduano Professor in Pediatrics at Weill Cornell Medicine and pediatrician-in-chief at NewYork-Presbyterian Komansky Children's Hospital.
Dr. Kristina De Paris, a professor in the Department of Microbiology and Immunology at UNC School of Medicine (搜索), serves as the main co-investigator of the project.
Overcoming HIV's Immune Evasion Strategies
HIV (搜索) has presented an insurmountable immunization challenge since its identification as the cause of AIDS (搜索) in 1983. The virus employs sophisticated evasion strategies, with its most accessible proteins mutating rapidly and its vulnerable entry structures shielded by antibody-resistant sugar molecules called glycans. While studies have identified rare antibodies that can neutralize HIV across multiple strains by targeting these vulnerable sites, developing a vaccine that can consistently elicit these broadly neutralizing antibodies has remained elusive.
The experimental vaccine is based on engineered versions of Env (搜索), HIV (搜索)'s outer-envelope protein complex, which is critical for the virus's infectivity. Through research spanning the last quarter-century, scientists led by Dr. John Moore, professor of microbiology and immunology at Weill Cornell Medicine, Dr. Rogier Sanders of Amsterdam UMC (搜索), and researchers at Scripps Research (搜索) have engineered stable versions of the Env trimer that retain the ability to elicit bnAbs.
BG505 GT1.1 SOSIP Trimer Technology
The vaccine utilizes the most recently optimized trimer structure, known as the BG505 GT1.1 SOSIP trimer (搜索). This engineered protein complex maintains the delicate three-part structure necessary for HIV (搜索) infectivity while remaining stable outside the viral context. The vaccine is designed to be administered in a series of inoculations that progressively direct the antibody response toward producing broadly neutralizing antibodies.
"This is good news for the potential success of the vaccine, as the number of boosts and length of time needed to achieve an effective anti-HIV (搜索) response make it optimal to place an HIV vaccine within the childhood vaccine schedule," Dr. Permar explained. "It may be that our only opportunity for an effective HIV vaccine is to test it as a childhood vaccine."
Research Optimization and Clinical Preparation
The funded research program will focus on optimizing multiple aspects of the vaccine in preparation for pediatric clinical trials in regions with high HIV (搜索) burden. Dr. Ashley Nelson, an assistant professor in the department of pediatrics at Weill Cornell Medicine, outlined the optimization strategy: "We'll be optimizing the dose of the Env (搜索) trimer protein complex and the general immune-boosting 'adjuvant' compound that we use in vaccines, as well as the number and schedule of inoculations."
A specialized sub-project led by Dr. Genevieve Fouda, professor of pediatrics at Weill Cornell Medicine, will examine potential interactions between the experimental HIV (搜索) vaccine and standard childhood immunizations. This research is particularly relevant for regions like sub-Saharan Africa, where vertical HIV transmission rates are high.
"In places like sub-Saharan Africa where the rate of vertical HIV (搜索) transmission is high, newborns could be protected by passive immunization with anti-HIV bnAbs during breastfeeding and would concurrently be given standard childhood vaccines," Dr. Fouda explained. "We will study whether these have any interaction with the experimental vaccine."