HIV Vaccine a step closer: Conquering a 50 year old pandemic!

Human Immunodeficiency virus or HIV which was first isolated and studied by scientists in 1980s, attacks the body’s immune system and is a virus which has no effective cure. Once a person gets infected, the have it for their complete life and makes entire body vulnerable to cancer and other life-threatening diseases. No HIV Vaccine is developed. Almost 38 million people in 2019 were living with HIV globally, and India ranked 3^rd in HIV epidemic with 2.1 million cases.

Up till today, there was no potential cure to this and even treatment for HIV may not be that promising for everyone. Now, the researchers have found an approach to produce first-of-a-kind HIV vaccines with such a novel approach, that it can revolutionize the sector.

The Hardships to be overcame for HIV Vaccine development

SARS-CoV-2 or corona virus uses a spike protein on its surface to penetrate through the host cells. In simpler manner, one subunit of spike protein bind to potential host cell and the other reserved subunit envelops around the target to spread through entire body. But with HIV, the case is different. Most of the surface of the virus is densely coated with sugar molecules that do not trigger any immune response. Also, the exposed parts are highly variable. And due to this, till now over 50 million different HIVs are around the world. This is both, devious and deadly.

Due to this, conventional approach to the development of a vaccine cannot be effective in the case of HIV vaccine. For this very reason, people have been infected and had been dying since past 5 decades of human evolution. Not anymore! 2021 would probably an end to this long wait…

Although there are millions of strains of this virus killing people, few parts of the spike do not change much with every strain. But obviously they are hard-to-access. After several years of research and observations, a theory was proposed. Antibodies which bind to these particular regions are called broadly neutralizing antibodies (bnAbs). They specifically could target a wide variety of HIV strains than ordinary antibodies that develop.

But, only in rare cases of HIV infection, people generate these antibodies naturally. Studying on those rarely generated bnAbs gave scientists opportunity to identify that exactly where does the antibodies bind to the virus. With this, they could develop “immunogens” to be used in vaccines.

The HIV Vaccine – Research at its best

The catch from the above “immunogen” development is that: only rare type of immature immune cells called naïve B cells can be developed to make bnAbs against HIV. Naïve B cells are found in plasma membranes which act as receptors to the incoming antigen. Only 1 in a million naïve B cells have potential to form bnAbs.

To overcome this issue, researchers at SCRIPPS Research and IAVI used a technique called germline targeting. Mainly there are four key steps involved in this type of germline targeting vaccine designing. Firstly, the structure and genetic information of the target antibody-antigen interaction. Then using bioinformatics, immunogens are developed which can bind to diverse precursors of antigen HIV.

After that, using preclinical immunogen, validation of isolating human B cell binders is done. And finally, the structural interaction with precursors is assessed; alongwith the experiments on mice. This approach potentially makes the work of human body easier as we can produce the rarely occurring bnAbs through vaccines. Also, as it targets the parts of spike proteins which do not change much, these types of vaccines can be applied on larger number of strains of HIV.

In phase I clinical trial, vaccine appeared to be safe and successfully effective on almost all the 48 healthy volunteers. The scientists at George Washington University in Washington D.C. and the Fred Hutchison Cancer Research Centre in Seattle, WA reported 97% success rate. For these all volunteers the injection of vaccine activated naïve B cells and thus stimulated the production of rare immune cells which start the process of antibody generation.

Although this trial was taken only on small mass of people and was not published in any research paper, the International AIDS society and HIV researchers acknowledged this feat on February 3, 2021 in an International Conference.

Announcement and Confirmation of Moderna

In response to the above success of HIV vaccine’s novel method of development; American Pharmaceutical giant Moderna, confirmed on April 15, 2021 that it will conduct phase 1 trials of HIV vaccines this year. This includes the beginning of three phase I trials of two HIV vaccine candidates, mRNA-1644 and mRNA-1574.

Among them, the former one is based on the novel method discussed here i.e., bnAbs based. Apart from SCRIPPS and IAVI, Bill and Melinda Gates Foundation (BMGF) are also collaborated in this research proceedings.

This strategy and approach can not only help in HIV treatment and prevention, but also can help in development of vaccines of other challenging pathogens such as influenza, dengue, Zika, hepatitis C viruses and malaria.

With such advancements and innovations, human evolution seems to be secure and mighty; yet covered with a cloud of hardships and difficulties.