Cross-posted from NIAID Newsroom

Decades of scientific advances have led to development and implementation of highly effective HIV treatment and prevention tools, strengthening optimism for achieving a durable end to the HIV pandemic. Yet a safe and effective preventive HIV vaccine remains elusive.

On HIV Vaccine Awareness Day 2020, NIAID honors the researchers and clinical study participants who play essential roles in advancing HIV vaccine development. While work toward an HIV vaccine continues, scientists also are addressing a new pandemic—coronavirus disease 2019 (COVID-19). NIAID is evaluating an investigational mRNA vaccine against COVID-19 in an early-stage clinical trial. Some platforms being used to develop COVID-19 vaccine candidates have their origin in HIV vaccinology.

“We emphatically state that finding safe, effective and durable vaccines for HIV and COVID-19 are NIAID’s top priorities. The world must have both,” NIAID Director Anthony S. Fauci, M.D., and his colleague Carl W. Dieffenbach, Ph.D., write in the Journal of the International AIDS Society. A commentary by the two experts reviews the state of HIV vaccine development and highlights future directions.

HIV is a uniquely challenging vaccine target, and scientists recognize that an HIV vaccine will need to trigger immune responses better than those produced naturally in response to HIV infection. Over the past decade, researchers have implemented three different approaches toward this goal.

One approach builds on information gleaned from the landmark RV144 study in Thailand, the only clinical trial to date to demonstrate efficacy, albeit modest, for an investigational HIV vaccine. However, the large-scale HVTN 702 clinical trial evaluating an updated version of the RV144 regimen among adults in South Africa was stopped in early 2020 when the regimen was found to be safe but ineffective at preventing HIV. This disappointing outcome may be attributable to differences between the HVTN 702 and RV144 study populations or to differences in the immune responses needed for protection against different global HIV subtypes, according to Drs. Fauci and Dieffenbach.

Another approach to an HIV vaccine is based on "mosaic" immunogens—vaccine components comprising elements from multiple HIV subtypes—that aim to induce immune responses against the wide variety of global HIV strains. Mosaic-based vaccine regimens are being evaluated in two late-stage clinical trials: Imbokodo (HPX2008/HVTN 705) and Mosaico (HPX3002/HVTN 706).

A third approach, still in preclinical studies, involves placing HIV genes into an unrelated carrier virus called cytomegalovirus (CMV) to elicit a cell-based immune response. A monkey version of the CMV-based vaccine protected roughly 50% of animals from sustained infection with SIV, the simian form of HIV. Efforts are underway to adapt this vaccine platform for testing in humans.

Scientists also are exploring ways to harness the potential of broadly neutralizing antibodies Exit Disclaimer(bNAbs) for long-acting HIV prevention tools and, ultimately, a vaccine. These antibodies can stop a wide variety of HIV strains from infecting human cells in the laboratory. The proof-of-concept Antibody Mediated Protection (AMP) Studies are evaluating whether intravenous infusions of the VRC01 bNAb can prevent HIV acquisition in people. In addition, the AMP Studies could clarify what level of bNAbs a vaccine or other long-acting HIV prevention method would need to achieve and maintain to provide sustained protection from the virus. In parallel, scientists are working to develop candidate vaccines that can elicit bNAbs in healthy people.

While work toward a safe and effective HIV vaccine continues, scientists also are pursuing other long-acting HIV prevention strategies. “We remain optimistic that effective interventions that people will reliably use can be developed and brought to scale,” Drs. Fauci and Dieffenbach conclude.

Reference:

CW Dieffenbach and AS Fauci. The search for an HIV vaccine, the journey continuesExit Disclaimer. Journal of the International AIDS Society. DOI: 10.1002/jia2.25506 (2020).