Safety and immunogenicity of two heterologous HIV vaccine regimens in healthy, HIV-uninfected adults (TRAVERSE): a randomised, parallel-group, placebo-controlled, double-blind, phase 1/2a study

Abstract

Summary Background Bioinformatically designed mosaic antigens increase the breadth of HIV vaccine-elicited immunity. This study compared the safety, tolerability, and immunogenicity of a newly developed, tetravalent Ad26 vaccine with the previously tested trivalent formulation. Methods This randomised, parallel-group, placebo-controlled, double-blind, phase 1/2a study (TRAVERSE) was done at 11 centres in the USA and one centre in Rwanda. Eligible participants were adults aged 18 to 50 years, who were HIV-uninfected, healthy at screening based on their medical history and a physical examination including laboratory assessment and vital sign measurements, and at low risk of HIV infection in the opinion of study staff, who applied a uniform definition of low-risk guidelines that was aligned across sites. Enrolled participants were randomly assigned at a 2:1 ratio to tetravalent and trivalent groups. Participants in tetravalent and trivalent groups were then further randomly assigned at a 5:1 ratio to adenovirus 26 (Ad26)-vectored vaccine and placebo subgroups. Randomisation was stratified by region (USA and Rwanda) and based on a computer-generated schedule using randomly permuted blocks prepared under the sponsor's supervision. We masked participants and investigators to treatment allocation throughout the study. On day 0, participants received a first injection of tetravalent vaccine (Ad26.Mos4.HIV or placebo) or trivalent vaccine (Ad26.Mos.HIV or placebo), and those injections were repeated 12 weeks later. At week 24, vaccine groups received a third dose of tetravalent or trivalent together with clade C gp140, and this was repeated at week 48, with placebos again administered to the placebo group. All study vaccines and placebo were administered by intramuscular injection in the deltoid muscle. We assessed adverse events in all participants who received at least one study injection (full analysis set) and Env-specific binding antibodies in all participants who received at least the first three vaccinations according to the protocol-specified vaccination schedule, had at least one measured post-dose blood sample collected, and were not diagnosed with HIV during the study (per-protocol set). This study is registered with Clinicaltrials.gov , NCT02788045 . Findings Of 201 participants who were enrolled and randomly assigned, 198 received the first vaccination: 110 were in the tetravalent group, 55 in the trivalent group, and 33 in the placebo group. Overall, 185 (93%) completed two scheduled vaccinations per protocol, 180 (91%) completed three, and 164 (83%) completed four. Solicited, self-limiting local, systemic reactogenicity and unsolicited adverse events were similar in vaccine groups and higher than in placebo groups. All participants in the per-protocol set developed clade C Env binding antibodies after the second vaccination, with higher total IgG titres after the tetr...

Safety and efficacy of COVID-19 vaccines in multiple sclerosis patients

“…To date, there are no reports of viral vector vaccines in patients with immune-mediated diseases. However, further insight into their safety can be gleaned from studies on the approved Ebola vaccine ( Pollard et al, 2020 ) and a human immunodeficiency virus (HIV) candidate vaccine ( Baden et al, 2020 ) using the same Ad26 vector technology. One participant developed small fiber neuropathy two weeks after receiving the Ebola vaccine and one developed rheumatoid arthritis four months after receiving one of the HIV candidate vaccines.…”

“…One participant developed small fiber neuropathy two weeks after receiving the Ebola vaccine and one developed rheumatoid arthritis four months after receiving one of the HIV candidate vaccines. Both events were deemed possibly related to the respective vaccines ( Baden et al, 2020 ; Pollard et al, 2020 ). Taken together, these adverse events along with the reported TM and MS events in the COVID-19 viral vector vaccine trials suggest a small potential for immune-mediated and neurological adverse events.…”

Variant SARS-CoV-2 mRNA vaccines confer broad neutralization as primary or booster series in mice

“…3,4 Vaccination with two 100 µg doses of mRNA-1273 4weeks apart was 94% efficacious against symptomatic COVID-19 disease; mRNA-1273 was granted Emergency Use Authorization (EUA) by the Food and Drug Administration in December 2020. 5,6 The emergence of SARS-CoV-2 variants with substitutions in the receptor binding domain (RBD) and N-terminal domain (NTD) of the viral S protein has raised concerns among scientists and health officials. [7][8][9][10] The entry of coronavirus into host cells is mediated by interaction between the RBD of the viral S protein and the host receptor, angiotensin-converting enzyme 2 (ACE2).…”

Poststudy Point-of-Care Oral Fluid Testing in Human Immunodeficiency Virus-1 Vaccinees

“…A subset of plasma samples from participants who enrolled in the Phase 1/2a HVTN 117/HPX2004 vaccine study [ 17 ] were assayed using the OraQuick ADVANCE Rapid HIV-1/2 Antibody Test (OraSure Technologies, Inc., Bethlehem, PA) as per manufacturer’s instructions for blood testing [ 18 ]. The OraQuick immunoassay platform uses gp41- and gp36-derived antigens for detection [ 19 ].…”

“…The OraQuick immunoassay platform uses gp41- and gp36-derived antigens for detection [ 19 ]. Participants had been randomized to 2 doses of either adenovirus serotype 26 (Ad26) delivering trivalent or tetravalent mosaic HIV immunogens followed by 2 doses of the same Ad26 in combination with clade C Env gp140 or placebo [ 17 ]. These plasma samples had been designated for evaluation of HIV seroreactivity (EOS) and were drawn at a participant’s end-of-study (final) visit, 24 weeks after their final vaccination.…”