Scientists at Emory University have made an important discovery that could help immunologists design vaccines that are more effective in protecting against HIV infection.
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Several non-human primate studies looking at HIV's relative – SIV – provided evidence that creating too many soft targets can weaken vaccination that would have otherwise protected against infection.
HIV targets T helper cells
HIV targets and replicates in immune cells called T helper cells, which aid the body's immune response to viruses.
As reported in the journal Science Translational Medicine, the researchers have now shown that an HIV vaccine must not create more safe havens for the virus than it does defenses that will protect against it.
Senior author Rama Rao Amara says the good news is that researchers can see early-on whether the immune system is heading down the wrong track.
"It's a matter of stimulating just the right amount of immune help for a strong immune response, but not so much that it increases susceptibility to the virus," says co-author Eric Hunter.
The problem arises when too many type 1 T helper cells are produced
The problem arises when vaccination results in the production of too many type 1 T helper (TH1) cells.
These cells migrate to mucosal tissues in the rectum, cervix, and vagina, where HIV or SIV usually first gain access to the body.
The Th1 cells are first-responders to an invading virus. Initially, they fight the virus, but then they get taken over. Amara says that what is needed instead is Tfh cells since these cells stay in the lymph nodes where they help the immune system produce virus-fighting antibodies.
"We're not saying Th1 cells are bad," says Amara… "But if you have too many, they take away from effective vaccine protection."
Previously, immunologists had suspected that vaccinating against HIV may be counterproductive, which led to the HVTN 502/STEP clinical trial that evaluated the safety and efficacy of an investigational HIV vaccine between 2004 and 2007.
Since then, however, scientists in the field of vaccine development have learned a great deal and are optimistic. Large-scale clinical trials are now underway following the success of a study conducted in Thailand ten years ago called the RV144 trial.
We need to build information about how adjuvants steer the immune response into future clinical studies. Vaccine efficacy depends not only on the magnitude of the immune response but also on its quality."
Senior author Rama Rao Amara
Adjuvants are components within vaccines that improve the immune response, and some research is now looking at combining adjuvants with synthetic copies of parts of HIV.
Studying vaccinated macaques
For the current study, Amara and the team collected data from four studies of macaques that were vaccinated to protect against infection with SIV or the hybrid SHIV virus.
The viruses were introduced to the monkeys, either intravaginally or intrarectally – the two most common infection routes in humans.
Among the animals that were challenged with SHIV intravaginally, the animals with a high Th1 level showed no delay in becoming infected, compared with animals that had not been vaccinated. However, the animals with a low Th1 level did exhibit some protection against infection, with two of seven animals still remaining uninfected after eight challenges.
Similar was observed among animals that were challenged intrarectally with SIV. Significant protection against the virus was observed, but only among the macaques that had low levels of Th1.
Vaccine developers should investigate whether they are generating too many Th1 cells
The researchers found that Th1 cells identified as compromising were more likely to reside in mucosal tissue rather than in the blood, where they could be difficult to detect.
Amara recommends that scientists researching candidate HIV vaccines in humans investigate whether they are generating too many Th1 cells. However, that could be challenging if mucosal tissue samples need to be taken from participants.
"A few months after vaccination, we saw it's difficult to see the Th1s in the blood, compared with the mucosa," says Amar… "But we could see a gene expression signature in the blood, one week after priming, which gave us a prediction of what will be in the mucosal tissues later."
Amara says this information could help immunologists design vaccines that provide more reliable protection against HIV.
Creating viral targets can weaken HIV vaccination. Eurekalert. Available at: https://www.eurekalert.org/emb_releases/2019-11/ehs-cvt111519.php