A new study presented a novel type of vaccine for HIV. The vaccine uses two parts of the immune response and was tested to provide improved and sustained protection against the disease.
The novel HIV vaccine type was revealed by researchers at Stanford Medicine, the medical school of Stanford University. Their vaccine model could awaken a part of the immune system, which is normally put to sleep by other models. As such, their novel approach could be a breakthrough in vaccine research for other viruses, including coronaviruses. They published the results in the journal Nature Medicine.
Why is it Difficult to Create a Vaccine for HIV?
Since the discovery of many aspects of HIV, research groups have been creating vaccine formulas that may provide some level of protection in people, if not complete immunity. However, vaccine research for the virus is challenged by a variety of factors. One of the greatest challenges has been the mutation rate of the virus. Scientists consider HIV to have the highest mutation rate than any known organism in the world. Its mutation rate could throttle different strains of the influenza virus.
According to NAM Aidsmap, an online resource for HIV and AIDS news, with such a high mutation rate, HIV can easily evade antibodies designed to disable it. Once the pathogen detects antibodies heading its way, it will configure itself to neutralize antibodies. This renders the vaccine useless. Moreover, vaccines tend to use either dead or live viruses to activate the adaptive immune response, which produces antibodies. But the inclusion of HIV in vaccines poses a huge risk of infecting healthy cells and promoting new copies of the virus in a person.
Aside from its mutation rate, HIV has several subtypes in human circulation. The two main types are HIV-1 and HIV-2 that both can cause acquired immune deficiency syndrome or AIDS. While the two are very different from one another, HIV-1 is the most common type in human communities. In terms of disease and transmission, research suggests that HIV-2 often progresses slower than AIDS and is less likely to be transmitted, compared to HIV-1. Because of that, it is important to determine the common denominator between these types in vaccine development.
Despite the challenges in HIV vaccine research, scientists do not stop looking for new insights. They simply have to find an exploitable loophole in the genetic structure and processes used by HIV. That loophole may allow the development of a functional vaccine capable of shielding a person for years.
According to Our World in Data, an online source of research data, the availability of antiretrovirals significantly decreased HIV/AIDS-related mortality. In 2017, the global total of mortality due to HIV/AIDS was 954,492, lower than 1.04 million in the previous year, and 1.12 million in 2015. Those numbers were substantially lower than the 1.95 million deaths in 2006 and 2005, and 1.91 million deaths in 2004.
New Vaccine Model Combines Two Portions of the Immune System
At Stanford Medicine, a group of researchers developed a novel vaccine model for HIV. Their design was in contrast to other vaccine models being investigated. Instead of putting a part of the immune system to sleep, their vaccine wakes that portion to support another immune response. Through the combination of two immune responses, the vaccine would induce immune cells to track down and destroy cells infected by HIV.
"Most vaccines aim at stimulating serum immunity by raising antibodies to the invading pathogen. This vaccine also boosted cellular immunity, the mustering of an army of immune cells that chase down cells infected by the pathogen. We created a synergy between these two kinds of immune activity," said Dr. Bali Pulendran, the corresponding author of the study and professor of pathology, and of microbiology and immunology at Stanford.
Typically, vaccines are tailored to wake up the adaptive side of the immunity. The killed or weakened viral particles in the vaccine will rile up the immune system to produce antibodies. Once the particles have been analyzed, the immune system will release the perfect antibodies. As a result, the body has memorized the viral signature and will generate appropriate antibodies should the virus be encountered in the future.
But in an HIV vaccine, adaptive immunity would be more costly and likely to fail due to the virus' mutation rate. So, Stanford researchers utilized cellular immunity and integrated it into adaptive immunity. Their vaccine model involved a two-armed approach wherein both serum and cellular immunity would be activated at the same time, meaning the vaccine would call the production of antibodies and killer T cells, which could destroy virus-infected cells.
Three groups of 15 rhesus monkeys were used to test the vaccine model. The animals were immunized and monitored for 40 weeks. The first group of monkeys was given multiple vaccines of Env, the protein on the outer surface of HIV. The protein could stimulate the immune system to produce antibodies. The same group was also administered with an adjuvant to boost the immune response.
The second group was immunized with Env and adjuvant as well but had extra injections comprised of different viruses. The additional viruses were modified to be infectious, yet nonlethal to the animals. Each of the viruses contained a gene called Gag to stimulate a cellular immune response. And finally, the third group served as a control that received injections with an adjuvant only.
After 40 weeks, the animals were permitted to rest for another 40 weeks. Then, the monkeys were given booster shots of Env vaccines only. They were allowed to rest again for 40 weeks before they were exposed to 10 weekly shots of SHIV, the counterpart of HIV in monkeys. Monkeys that received the adjuvant only were infected by SHIV, while monkeys exposed to both Env and Env with Gag exhibited significant initial protection.
But the only monkeys that were administered with Env and Gag had extended protection. Despite the lack of high levels of antibodies for SHIV, the said monkeys managed to fight the pathogen. This showed a critical detail for immunologists who commonly consider serum-based immune response as the basis of a vaccine's efficacy.
To further prove their concept, researchers exposed the Env only group and the Env plus Gag group to extra SHIV shots. Six monkeys from both groups were exposed to the virus. Out of Env only group, only one remained uninfected but in the Env plus Gag group, four monkeys sustained immunity.
Researchers theorize that their vaccine model may have stimulated the production of tissue-resident memory T cells. These immune cells often guard the entry sites of viruses and stay in those sites for an extended period. During their stay, they monitor the presence of the viruses and if they detect the same virus types, they signal other immune cells to turn nearby tissues aggressive to viruses.