The results are very important for immunologists who are tracking coronavirus vaccines and better vaccines against other diseases, Bali Pulendran said.
The key to significantly increasing the protection of new vaccines against viral infections lies in their ability, unlike almost all vaccines currently used, to awaken the part of the immune system that most vaccines currently sleep on.
“Most vaccines aim to stimulate serum immunity by increasing antibodies against invading pathogens,” Pulendran said of antibodies circulating in the blood.
“This vaccine also strengthens cellular immunity, the accumulation of forces of immune cells that fight cells infected with pathogens. We have created synergies between these two types of immune activity.”
Around 38 million people around the world live with AIDS, the inevitable fatal disease caused by HIV. Although HIV can be controlled by a combination of antivirals, HIV continues to infect 1.7 million people per year and causes around 770,000 deaths each year.
The vaccine is said to stimulate the adaptive immune system, which then produces cells and molecular weapons that target certain pathogens, rather than firing at anything that moves, bad or bad.
But most vaccines drive the adaptive immune system to fight infection with one hand tied behind the back.
“All previously approved vaccines induce antibodies that neutralize the virus. However, encouraging and maintaining a fairly high level of neutralization of antibodies to HIV is a difficult task, “Pulendran said.
“We have shown that stimulating the cellular framework of the immune system can give you greater protection against HIV, even when there are far less neutralizing antibodies.”
They inoculated three groups of 15 rhesus monkeys for 40 weeks.
The first group received several consecutive vaccinations with Env, proteins on the outer surface of the virus that are known to stimulate antibody production, and adjuvants, chemical combinations that are often used in vaccines, to enhance the overall immune response.
The second group was vaccinated in a similar manner, but received additional injections of three types of virus, each modified as an infection but not dangerous.
Each modified virus contains additional genes for viral proteins, vomiting, which are known to stimulate cellular immunity.
The third group, the control group, received injections containing only adjuvants.
At the end of the 40-week regime, all animals were allowed to rest for a further 40 weeks, after which they only received a refreshing picture of the Env inoculation. After a four-week break, they were exposed to SHIV, a similar version of HIV, for 10 weeks.
Monkeys that only accept adjuvants are only infected. Animals in the Env and Env plus Gag groups experienced significant initial protection against viral infections.
Even more remarkable is the extension of the protection period in animals that receive the Env-plus-Gag combination. After a 20-week break, six monkeys from the Env group and six from the Env group plus a gag received additional exposure to SHIV. This time, four Env-plus-Gag animals, but only one of the Env animals, remained uninfected.
Pulendran suspected that the increase was caused by the production of immune cells stimulated by a vaccine called resident-memory T cells.
These cells migrate to where the virus penetrates the body and park there for a long time and function as a clock. When they see the virus again, these cells react and produce factors that indicate other types of immune cells around them to turn tissue into an enemy area for the virus.
“These results indicate that future vaccination efforts should focus on strategies that bring cellular and antibody responses that provide excellent protection not only against HIV but also against other pathogens such as tuberculosis, malaria and hepatitis C virus. “Influenza and the coronavirus pandemic also follow,” Pulendran said.
Reference: The research was funded by the National Institutes of Health (grants UM1AI124436, U19AI110663, HIVRAD P01AI110657 and ORIP/OD P51OD01132) and the Bill and Melinda Gates Foundation. Stanford’s Department of Microbiology and Immunology also supported the work.