MEXICO CITY – A "mosaic" vaccine against HIV was well-tolerated and able to produce an immune response against multiple clades, or disease subtypes, in healthy volunteers, a researcher said here.
Adding a mosaic gp140 protein to the existing vaccine both improved response to clade B, the predominant HIV subtype found in the Americas and Europe, and did not impact responses against clade C, which is mostly found in Africa, reported Hanneke Schuitemaker, PhD, of Janssen Vaccines & Prevention in the Netherlands.
"Interestingly, adding [the protein] to the regimen resulted in improved immune responses to a wide range of clades," she said at a press conference at the 10th International AIDS Society (IAS) Conference on HIV Science. She added that both this proof-of-concept study, and another called APPROACH, "are the latest in early stage studies that suggested [the vaccine] was well-tolerated with a good safety profile, and the ability to produce an immune response to HIV."
Despite all the success of pre-exposure prophylaxis (PrEP) in preventing HIV, Anthony Fauci, MD, director of the National Institute for Allergy and Infectious Diseases (NIAID), which helped to fund the research, told MedPage Today that development of a vaccine is still critically important for HIV prevention.
"We have the tools right now, if properly and aggressively and completely implemented, [that] could lead to the ending of the epidemic as we know it. However, that is theoretical," he said. "If you want to durably control the epidemic ... you need a mechanism that has been proven time and time again -- one or two or three shots in the arm and you're done."
"If you're talking about universal, global, durable control of the epidemic, we absolutely need a vaccine," Fauci added.
In fact, the ASCENT trial was launched to "further optimize the vaccine regimen to improve on coverage of clade B strains," Schuitemaker said. Researchers developed a mosaic gp140 protein (Mosaic1 gp140) and set out to discover if adding this protein to the existing vaccine would attenuate the vaccine's response against clade C.
When examining two groups -- one receiving the last two doses of existing vaccine with the clade C gp140 protein, and one receiving a vaccine with a bivalent protein, where half the clade C dose was replaced with the mosaic protein -- they found that a significant improvement in response to clade B, and clade C responses "were not attenuated," the researchers said.
"Other vaccines have often been in one region or one subtype. The vaccine being studied right now ... would most likely be a globally relevant vaccine," Mitchell Warren, executive director, AVAC: Global Advocacy of HIV Prevention, who was not involved in the research, told MedPage Today. "We are making huge scientific progress."
Phase III and Beyond
On July 15, the NIH announced a phase III efficacy trial for the mosaic vaccine (HPX3002/HVTN 706 or Mosaico) among 3,800 HIV-negative men who have sex with men (MSM) and transgender people ages 18-60 in sites across Latin America and Europe. This is in addition to the ongoing complementary phase IIb study (HPX2008/HVTN 705 or Imbokodo) of the vaccine that was launched in 2017 among women in southern Africa.
Warren noted that for decades, vaccine research has mostly been funded by the NIH, the Gates Foundation, and the U.S. Agency for International Development (USAID), with industry "involved as partners, but often using public sector and philanthropic dollars." However, Mosaico is sponsored by Janssen Vaccines & Prevention, which means a pharmaceutical company is investing their own resources in it, he added.
"Companies don't invest because it's cool science, they invest because they believe there's a product to develop," Warren said. "Industry [is] interested. I think that's critically important."
But as trials for this and other vaccines progress, Paul Volberding, MD, an HIV physician in San Francisco, who was not involved with the research, sounded a note of caution.
"Vaccine trials are really, really difficult because we have other prevention that works so well, and if you put someone on a vaccine trial, you have to ethically make sure they understand about PrEP and condoms ... you have to do your best not to get them infected ... the better you do, the harder it is to show that a vaccine works," he told MedPage Today. "Even if these work as well as one could imagine, it's going to be years before they hit the scene."
Indeed, Schuitemaker said that results from Imbokodo will not be available until 2021, with Mosaico results not expected until 2023.
In the phase IIa ASCENT trial, researchers examined data from 152 healthy adults, 59% of whom were women, in Kenya, Rwanda, and the U.S. Participants were randomized to receive Ad26.Mos4.HIV (the mosaic vaccine) or placebo at weeks 0 and 12, and Ad26.Mos4.HIV and clade C gp140 or Ad26.Mos4.HIV and bivalent gp140 (which included the new Mosaic1 gp140 protein) at weeks 24 and 48.
Overall, 26 participants were vaccinated with Ad26.Mos4.HIV and clade C gp140; 100 were vaccinated with Ad26.Mos4.HIV and bivalent gp140; and 26 received placebo.
At week 24, T cell Intracellular Cytokine Staining assay responses increased to Mosaic1 gp140 peptides in the bivalent versus the clade C group, the authors said, with 81% and 50% response rates, respectively.
This study was supported in part by Janssen Vaccines & Prevention and the NIH.
Stieh and Schuitemaker are employees of Janssen Vaccines & Prevention.
International AIDS Society
Source Reference: Stieh DJ, et al "ASCENT: Phase 2a, randomized, double-blind, placebo controlled study evaluating safety and immunogenicity of two HIV-1 prophylactic vaccine regimens comprising Ad26.Mos4.HIV and either clade C gp140 or bivalent gp140" IAS 2019; Abstract 4979.