May 22, 2026 —
A new paper published in Human Vaccines & Immunotherapeutics, titled “Could AAV-vectored delivery of broadly neutralizing antibodies (bNAbs) reduce virologic failure in children diagnosed with perinatal HIV?”, discusses whether AAV-vectored delivery of broadly neutralizing antibodies, or bNAbs, could reduce virologic failure in children diagnosed with perinatal HIV.
Antiretroviral therapy has transformed HIV into a manageable chronic condition, but its success depends on lifelong adherence, reliable access to medication, and continuous clinical follow-up. These requirements are especially challenging for children living with HIV and their caregivers, particularly in resource-limited settings where treatment interruptions and limited viral load monitoring remain major barriers.
Broadly neutralizing antibodies offer a complementary strategy by directly neutralizing diverse HIV-1 strains. Clinical studies have shown that passive bNAb infusion can help maintain viral suppression in some children after ART withdrawal. However, repeated administration of antibody biologics is costly and difficult to scale in regions with high rates of vertical HIV transmission.
The paper highlights AAV-mediated bNAb delivery as a potential way to overcome this limitation. Instead of repeatedly administering recombinant antibodies, AAV vectors can deliver genetic instructions to long-lived host cells, such as skeletal muscle, enabling sustained in vivo antibody production after a single intramuscular administration.
Preclinical studies in rhesus macaques have shown that neonatal AAV delivery can support multi-year bNAb expression with limited anti-drug antibody responses. In SHIV challenge models designed to mimic HIV transmission through breastfeeding and sexual exposure, AAV-expressed bNAbs provided significant protection against infection.
The authors note that the neonatal setting may offer unique advantages, including a more tolerogenic immune environment and a developmental window when maternally acquired anti-AAV antibodies decline. These features may support durable antibody expression and improve the feasibility of early-life intervention.
Key challenges remain, including bNAb immunogenicity, HIV sequence diversity, viral escape, AAV manufacturing capacity, pre-existing vector immunity, redosing limitations, and the need for long-term safety monitoring. The article also discusses complementary non-viral genetic antibody delivery platforms, which may offer advantages in repeat dosing and rapid antibody redesign.
Overall, the paper positions AAV-vectored bNAb expression as a promising long-acting approach for both pediatric HIV prevention and durable ART-free virologic control in children living with HIV. While clinical validation is still needed, the strategy could help reduce dependence on lifelong ART and support more scalable HIV care in global pediatric populations.
