Because vaccines are usually given to healthy people, there are strict standards to which vaccine development must adhere and higher thresholds for measuring safety. Before a vaccine is allowed to be tested in humans, it has to show potential for triggering an immune response; this is done in pre-clinical testing in animals. Human (clinical) testing then proceeds in three stages to ensure that the vaccine is safe and effective:
Phase 1
Phase 1 is a safety study that involves giving the vaccine to a small group of people (around 100) to ensure that there is no harm and to see if it provokes an immune response.
Phase 2
Phase 2 is a larger safety study with hundreds of people to learn more about safety in diverse populations and the most appropriate dosage.
Due to the high cost of Phase 3 trials, vaccines can be studied in a Phase 2b trial in order to see more quickly if there is any efficacy before committing to a much larger Phase 3 study.
Phase 3
Phase 3 is a final study whereby the vaccine is compared against a placebo to measure how effective it is at preventing infection. These studies enrol thousands of people and can detect rarer side-effects. Phase 3 trials are randomized and double-blinded: neither the researchers nor the participant knows if a participant receives the vaccine or placebo. If found to be safe and effective, the vaccine can be marketed.
Imbokodo and Mosaico are sister studies testing similar vaccines using a “prime-boost” approach designed to protect against all HIV strains (clades). In these trials, the prime is a viral vector carrying synthetic versions of HIV genes and the boost is a synthetic HIV protein.
Mosaico (HVTN 706) is a four-year Phase 3 trial in 3,800 men and transgender people who have sex with men in eight countries across Europe, North America and South America.
Imbokodo (HVTN 705) is a five-year Phase 2b study in 2,637 women in five countries in sub-Saharan Africa.
The vaccines being evaluated in Imbokodo and Mosaico use the following components that have shown promise in earlier studies:
Ad26 is a viral vector based on a type of human adenovirus, a mild virus that causes the common cold. This vector is a genetically modified, weakened version of the virus so it cannot cause illness. Ad26 is used to carry synthetic versions of three HIV genes that are found in HIV strains circulating in several regions around the world.
Clade C gp140 is a synthetic HIV protein specific to Clade C, the version of HIV that is most common in southern Africa and India.
Imbokodo and Mosaico use slightly different versions of “mosaic” vaccines that incorporate genetic material from a wide variety of HIV clades. Imbokodo participants receive Ad26.Mos4 vector as well as a clade C envelope protein. Mosaico participants receive the same regimen augmented by an additional “mosaic” envelope protein to broaden immune responses.
Janssen Vaccines & Prevention B.V., part of the pharmaceutical company, Johnson & Johnson, sponsor Imbokodo and Mosaico in partnership with the HIV Vaccine Trials Network (HVTN) and the US National Institute of Allergy and Infectious Diseases (NIAID). Earlier clinical studies were also supported by the Bill & Melinda Gates Foundation.
The results of Imbokodo are expected in late 2022, with Mosaico concluding a year later.