The results from the HVTN097 trial build upon the results of the RV144 trial
The investigational HIV vaccine regimen that showed a modestly protective effect in the landmark RV144 clinical trial conducted in Thailand was shown to be safe and elicited robust immune responses when tested among 100 healthy adults in South Africa, according to findings presented today at the HIVR4P conference in Cape Town, South Africa. The results from the trial, called HVTN 097, bode well for plans to test a similar experimental vaccine regimen in South Africa beginning in 2015 in an effort to build upon the results of the RV144 study.
The National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health, sponsored the HVTN 097 study. It was conducted through the NIAID-funded HIV Vaccine Trials Network (HVTN).
“The HVTN 097 study clearly shows that the investigational HIV vaccine regimen is safe in South Africans and induces comparable if not somewhat stronger immune responses than seen among Thais in the RV144 trial,” said NIAID Director Anthony S. Fauci, M.D. “The findings are encouraging as we move toward evaluating a modified and potentially improved version of the vaccine regimen in South Africa.”
The RV144 Phase III clinical trial tested the safety and effectiveness of a prime-boost regimen of two vaccines in more than 16,000 adults in Thailand. The regimen consisted of: ALVAC-HIV vaccine (the primer), a modified canarypox vaccine developed by Sanofi Pasteur, based in Lyon, France; and AIDSVAX B/E vaccine (the booster), a glycoprotein 120 vaccine developed by Vaxgen Inc. and now licensed to Global Solutions for Infectious Diseases (GSID), based in South San Francisco, CA. The vaccines were based on HIV subtypes (called clades) B and E, the common HIV strains in Thailand. In 2009, Army researchers announced that the vaccine regimen was 31 percent effective at reducing the risk of HIV infection among vaccinated participants by the conclusion of the study. Notably, the RV144 vaccine regimen may have provided greater protection against HIV acquisition sooner after vaccination, but the effect waned over time. The potential for an early, robust immune response suggests an additional boost or augmentation of immune response would improve efficacy.
Since 2009, scientists have conducted broad analyses of the RV144 data and have gained insight into the types of antibodies and cellular immune responses a preventive HIV vaccine may need to induce. NIAID and its collaborators in the Pox-Protein Public-Private Partnership (called P5) have been working to build on the RV144 results in an effort to advance and potentially license HIV pox-protein vaccine candidates that have the potential to achieve a broad public health impact.
“Vaccines specifically designed to elicit immune responses more closely directed to the circulating strains of HIV in sub-Saharan Africa have been constructed,” said Larry Corey, M.D., HVTN principal investigator. “Clinical trials of these HIV subtype C vaccines that are based upon those used in RV144 and HVTN097 are planned to begin in South Africa in early 2015.” The upcoming trials will seek to improve and prolong the level of protection seen in RV144 by using an extra vaccine boost and different adjuvants that may increase and extend the duration of antibody responses.
The HVTN 097 trial provides the scientific underpinning for moving forward with the South African clinical trials. In the findings announced at the HIVR4P conference, lead investigator Glenda Gray, HVTN co-principal investigator and president of the South African Medical Research Council, said that the vaccine regimen was safe when tested among 100 HIV-uninfected South Africans at three clinical trial sites in Soweto, Cape Town and Klerksdorp. Additionally, the vaccine regimen induced CD4+ T-cell responses that were at least comparable to or better than those induced in the RV144 study. Moreover, age, gender, and body mass index had no effect on immune response rates—a critical point because earlier research has demonstrated that those factors can impact vaccine-induced responses. Vaccine-induced antibody responses also appeared to be favorable but continue to be evaluated, according to Gray.