The phase 2a study compares a bivalent combination of Clade C and Mosaic gp140 with a single-valent Clade C gp140.
Formulating a preventive vaccine for HIV-1 infection has proved elusive for investigators who must contend with the diverse strains of the virus circulating the globe.
But results from the ongoing phase 2a ASCENT study, which were presented at the 10th IAS Conference on HIV Science (IAS 2019), demonstrate that 2 investigational mosaic-based prophylactic vaccine regimens intended to prevent HIV-1 infection induced high immune responses against a broad range of virus strains.
Janssen’s investigational HIV vaccination regimen comprises 4 visits over 1 year—the first 2 visits involve a single injection of tetravalent mosaic-based adenovirus serotype 26 vector (Ad26.Mos4.HIV), while the final 2 visits involve Ad26.Mos4.HIV plus an injection of a soluble trimeric gp140 protein adjuvanted by aluminum phosphate, according to a Johnson & Johnson press release.
In the randomized, double-blind, placebo-controlled ASCENT study, investigators sought to compare a bivalent combination of Clade C and Mosaic gp140 with a single-valent Clade C gp140. A total of 152 healthy adults (18-50 years; 59% females) in Kenya, Rwanda, and the United States were randomized to Ad26.Mos4.HIV at weeks 0 and 12, and Ad26.Mos4.HIV and alum adjuvanted gp140 Env protein (250 µg clade C gp140 or bivalent clade C-Mosaic1 gp140, each 125 µg) at weeks 24 and 48 or placebo.
Twenty-six participants received Ad26.Mos4.HIV and clade C gp140, while 100 participants received Ad26.Mos4.HIV and bivalent gp140. Twenty-six others received placebo.
Both active regimens were well-tolerated and immunogenic, with no serious adverse events reported. Notably, bivalent gp140 produced enhanced immune responses to Clade B, which is the prevalent subtype in the Americas, Western Europe and Australasia.
“HIV Env-specific binding antibody levels and subclass distribution showed both regimens induced binding and functional antibodies to all antigens tested. Clade C responses were not attenuated by replacing half the clade C dose with Mosaic1 gp140, while clade B responses improved (p< 0.05),” investigators reported.
“At week 28, similar PTE Env ELISpot responses were observed, with medians of 444 and 452 SFU/106 PBMC in bivalent or clade C groups, respectively. CD4+ (but not CD8+) T-cell ICS responses increased to Mos1 gp120 peptides in the bivalent relative to clade C group (0.147% vs 0.123% IL-2 and/or IFNγ+ CD4 T-cells, 81% vs 50% response, respectively),” the research team concluded.
The ASCENT trial results support the use of bivalent clade C-Mosaic1 gp140 with Ad26.Mos4.HIV, and will be further studied in the recently announced phase 3 study called Mosaico.
“This mosaic-based vaccine regimen is designed as a global vaccine with the goal of preventing infections from the wide range of viral strains responsible for the HIV pandemic,” Hanneke Schuitemaker, vice president and global head of Viral Vaccine Discovery and Translational Medicine at Janssen Vaccines & Prevention B.V., told Contagion®. “Mosaico is planned to be a 3800-person study of men who have sex with men and transgender people. The study will be conducted across 3 continents, 8 countries, and over 55 clinical trial sites. Enrollment is expected to begin in the United States later in 2019.”
Mosaico is sponsored by Janssen Vaccines & Prevention, B.V., part of the Janssen Pharmaceutical Companies of Johnson & Johnson, and supported by NIH’s National Institute of Allergy and Infectious Disease. Additional partners include the HIV Vaccine Trials Network and US Army Medical Research and Development Command.
The study, “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,” was presented Tuesday, July 23 2019, at IAS 2019 in Mexico City, Mexico.