wwwkkk83 发表于 2019-8-1 00:20:14

Mosaic’ HIV vaccine to be tested in thousands of people

‘Mosaic’ HIV vaccine to be tested in thousands of people across the world
The experimental vaccine targets more strains of the virus than any other ― and seems to have longer lasting effects.

An experimental HIV vaccine that targets more strains of the virus than any other developed so far will start a late-stage clinical trial later this year. The ‘mosaic’ vaccine, which incorporates genetic material from HIV strains from around the world, also seems to have the longest-lasting effects of any others tested in people.

Small trials of the mosaic vaccine in people showed that it prompted an immune response, such as the production of antibodies, against HIV. But starting in September, scientists will test it in thousands of people to assess whether the vaccine provides any protection against HIV infection. The phase III trial will test the vaccine in transgender individuals and in men who have sex with men across the Americas and Europe.

These communities are disproportionately affected by HIV, with about two-thirds of new infections in the United States occurring among gay and bisexual men, according to the US Centers for Disease Control and Prevention. The team running the trial, which they’ve named Mosaico, discussed the project during the 10th International AIDS Society Conference on HIV Science in Mexico City last week.

A new hope?
Adding an effective HIV vaccine to the arsenal of preventive measures currently available to protect people from infection, including condoms and an antiretroviral regimen called PrEP, could make a huge difference, says Susan Buchbinder, an epidemiologist at the University of California, San Francisco, who is part of the Mosaico team.

Some of the preventive methods — such as PrEP, which requires taking a daily pill — can be difficult for people to maintain or even access, says epidemiologist Jorge Sánchez from the Centre for Technological, Biomedical and Environmental Research in Lima, Peru, one of Mosaico’s research sites. A vaccine that requires a few shots every other year could be a good alternative for them, he says.

But researchers have struggled since the 1980s to find an effective HIV vaccine. One of the principal challenges is the incredible diversity of HIV strains circulating in the world. So far, scientists haven’t had much luck in developing a vaccine that can target such a diverse pathogen, says virologist Dan Barouch at the Beth Israel Deaconess Medical Center in Boston, Massachusetts.

More than 100 HIV vaccines have been tested in people in the past three decades, but only one has demonstrated any kind of protection. In 2009, researchers announced the results1 of a study conducted in Thailand that showed that shortly after participants received an experimental vaccine, they were almost 60% less likely to become infected with HIV than those given a placebo. But the effects waned within a year — by the end of the 3.5-year study, vaccinated individuals were only 31% less likely to become infected.

Small laboratory tests of the Mosaico vaccine in people showed that it elicited strong immune responses for at least two years after researchers administered it2. These responses seem to be more durable than those observed in the Thai vaccine trial, says Guido Silvestri, an AIDS researcher at Emory University in Atlanta, Georgia.

Cautiously optimistic
The latest Mosaico study will enrol 3,800 participants across 8 countries, including Argentina, Italy, Mexico, Poland and the United States. Half of the participants will get four vaccine injections over the course of a year, and the other half will receive a placebo.

The shots contain a disabled common cold virus that carries synthetic versions of three HIV genes. Researchers built the genes based on sequences from HIV strains found in several regions around the world. As an added boost to help the body produce antibodies against HIV, the Mosaico team added two synthetic proteins — based on proteins produced by HIV strains common in Africa, the Americas, Europe and Australasia — to the last two doses in the series. The incorporation of this “protein boost” is what makes this a truly global vaccine, says Barouch.

The Mosaico team hopes that their vaccine will help to protect at least 65% of the study participants. They expect to get results by 2023. The study is sponsored by a consortium led by Janssen Vaccines & Prevention, part of Johnson & Johnson of New Brunswick, New Jersey.

Some researchers are reserving judgement on Mosaico. HIV viruses can mutate rapidly, which can stymie any immune response a vaccine might prompt, says Tomáš Hanke, an immunologist at the University of Oxford, UK. To try to get around this problem, he’s attempting to create a mosaic vaccine that incorporates parts of the virus’s genetic code in which mutations rarely occur.

HIV researcher Ma Luo, at the University of Manitoba in Canada suspects that finding an effective vaccine will take longer than the Mosaico researchers think, but applauds their efforts. Learning from human trials is valuable, she says, no matter the outcome.

References
1.
Rerks-Ngarm, S. et al. N. Engl. J. Med. 361, 2209–2220 (2009).

PubMedArticle Google Scholar
2.
Barouch, D. H. et al. Lancet 392, 232–243 (2018).

https://www.nature.com/articles/d41586-019-02319-8

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