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

作者：Lindsey R. Baden, Daniel J Stieh, Michal Sarnecki, Stephen R. Walsh, Georgia D. Tomaras, James G. Kublin, M. Juliana McElrath, Galit Alter, Guido Ferrari, David C. Montefiori, Philipp Mann, Steven Nijs, Katleen Callewaert, Paul Goepfert, Srilatha Edupuganti, Etienne Karita, Johannes P. M. Langedijk, Frank Wegmann, Lawrence Corey, Maria Grazia Pau, Dan H. Barouch, Hanneke Schuitemaker, Frank Tomaka, Julie A. Ake, Susan Buchbinder, Karen Buleza, Kristen W. Cohen, Trevor A. Crowell, Zelda Euler, Ian Frank, Dimitri Goedhart, Michael C. Keefer, Colleen Kelly, Ken Mayer, Joseph P. Nkolola, Lauren Peter, Merlin L. Robb, Nadine Rouphael, Lorenz Scheppler, Magda Sobieszczyk, Hong‐Van Tieu · 发表于：The Lancet HIV · 年份：2020 · DOI：10.1016/s2352-3018(20)30229-0 · 被引用次数：93 · 研究领域：HIV Research and Treatment、HIV/AIDS oral health manifestations、Poxvirus research and outbreaks

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 r...