New HIV vaccine achieves robust immunity in monkeys and humans

Medicine

Monday, July 9, 2018

/ psdesign1, stockadobecom

Boston – A so-called mosaic vaccine containing antigens of various HI virus variants has a robust immune response in a first clinical trial achieved. According to animal studies that accompany it, the vaccine could protect two-thirds of all vaccinated subjects against infection. The results published in Lancet (2018, doi: 10.1016 / S0140-6736 (18) 31364-3) led to a follow-up study currently underway in five African countries

. The vaccine has proven difficult because the HI virus is highly variable and also infects CD4 cells, a central part of the immune system. After the first failures, a promising strategy was found ten years ago. It was a combined primer / booster vaccine

. Sanofi Pasteur's ALVAC-HIV DNA vaccine was used as a primer. It consists of a canarypox virus (which is harmless to humans), each being endowed with a version of HIV genes "env", "gag" and "pol." AIDSaxx has been used by VaxGen as a booster and contains the recombinant HIV virus. Gp120 Surface Protein

In the RV144 study, the combined ALVAC HIV / AIDSVAX vaccine achieved 31% protection (NEJM 2009; 361: 2209-20), and the efficacy was too low for to be approved. However, the RV144 study showed that the development of an HIV vaccine is not hopeless.

Among other developments, there are several mosaic vaccines from the manufacturer Janssen, whose primer contains HIV genes "env", "gag" and "In several versions that represent the different global variants of HIV (Clade) The carrier virus is a modified adenovirus serotype 26 (Ad26) .This primer was combined with various boosters in the APPROACH study.

A total of 393 healthy volunteers from the United States, Rwanda, Uganda, Africa South and Thailand, who were not infected with HIV, participated in the APPROACH study.The aim of the Phase 1 / 2a study was the tolerability of the vaccine. There were no safety concerns after the results reported by Dan Barouch of Harvard Medical School in Boston and colleagues The most common complaints were local reactions at the injection site that occurred in 69 to 88% patients, depending on the combination Grade 3 adverse events occurred in five of the 393 participants (1%). It was abdominal pain and diarrhea (with the same participant), an increase in aspartate aminotransferase, dizziness, back pain and discomfort.

In this context, the data are interesting for the immunity reached in the different groups. The best immunity was obtained by combining the Mosaic Ad26 primer with an amplifier containing the Mosaic Ad26 vaccine again and in addition a high dose of the gp140 surface protein. This combination produces antibodies against the Env protein in all patients, as well as 80% of an antibody-dependent cellular phagocytosis response and 83% of T-cell responses.

The researchers also compared the vaccine to 72 rhesus monkeys with placebo, The combination of the Ad26 primer and the 'Ad26 plus gp140' booster induces a human-type immune response and provides 67% protection against virus infection of the virus. 39 Human Immunodeficiency (SIM), which is the cause of HIV infection. Viruses in humans

The good results of the APPROACH study, presented last year at the 9th International Conference of the International AIDS Society on the science of HIV in Paris, have already aroused a follow-up study. Since November 2008, the HVTN 705 / HPX2008 Phase 2b study ("Imbokodo") is investigating whether the vaccine can protect against HIV infection in 2,600 young women ages 18 to 35 originating in five countries of sub-Saharan Africa. The first results of the study are expected for the year 2021. © rme / aerzteblatt.de