Vectored Immunoprophylaxis May Be a Valuable Tool in the Fight Against HIV/AIDS

Infected blood with HIV virus.
Virus infected blood cells.3d illustration.
Researchers assessed whether adeno-associated virus vectored immunoprophylaxis with AAV8-VRC07 produces broadly neutralizing antibodies in patients with HIV.

An intramuscular (IM) injection of AAV8-VRC07, a recombinant bicistronic adeno-associated viral vector, produced a significant concentration of biologically active HIV-1 broadly neutralizing antibodies (bnAbs) in patients with HIV infection, according to preliminary results of a phase 1, dose-escalation clinical trial published in Nature Medicine.

Investigators administered AAV8-VRC07 to adults with HIV infection who had been receiving antiretroviral therapy (ART) for at least 3 months. All included patients had an HIV viral load of less than 50 copies/mL and a CD4 count of at least 300 cells/µL. Patients received IM injections of AAV8-VRC07 at either a low-, intermediate, or high-dose of 5×1010, 5×1011, and 2.5×1012 vector genomes (vg)/kg, respectively. Patients in the low and intermediate dose groups received 2 injections, and those who received a high dose received between 7 and 9 injections. The primary objectives were to assess the safety and tolerability of AAV8-VRC07, understand the pharmacokinetics and immunogenicity of in vivoVRC07 production, and to assess the host’s immune response to AAV8-VRC07. Data from between weeks 104 and 194 following AAV8-VRCO7 administration were reported.

There were 8 adults included in the final analysis, of whom 6 were men, 2 were women, and the median age was 52 years. At the trial’s preliminary primary and secondary endpoints, patients did not report any significant adverse events related to AAV8-VRC07, and all product-related adverse events had resolved. Mild increases in baseline concentrations of aspartate transaminase and alanine transaminase were observed, both of which remained within the reference range.

There were less than 200 copies/ml of AAV8-VRC07 vector observed among patients in the low and intermediate dose groups at week 4, with similar results observed at week 28 among those in the high dose group. A rapid increase in AAV8 capsid-specific serum antibody titers was observed at different timepoints among the patient groups, indicating a dose-response relationship. Maximal serum concentrations of AAV8-VRC07 were achieved between weeks 8 and 16 for patients who received the low dose, at week 8 for those who received the intermediate dose and, and between weeks 2 and 12 for those who received the high dose.

There weres no significant changes in HIV viral load or CD4 T-cell count after AAV8-VRC07 administration.

All 3 patient groups produced measurable VRC07 with a characteristic expression pattern. Production of VRC07 was significantly increased at 6 (P =.008) and 52 weeks (P =.016) compared with pre-injection concentrations among all patients.  A new steady-state or a gradual increase in VRC07 concentration occurred in 4 patients for up to 2.5 years.

Anti-drug antibodies (ADA) against VRC07 Immunoglobulin G were found in 4 patients, but there was no effect on VRC07 neutralization activity. Of these patients, ADA were non-idiotypic in 3.

The major limitations of this study was its small sample size.

According to the researchers, “vectored immunoprophylaxis and immunotherapy offers a new means to safely produce bnAbs in humans that are difficult to elicit using current vaccine methodology.”


Casazza JP, Cale EM, Narpala S, et al. Safety and tolerability of AAV8 delivery of a broadly neutralizing antibody in adults living with HIV: a phase 1, dose-escalation trial. Nat Med. Published online April 11, 2022. doi:10.1038/s41591-022-01762-x