A 30-year-old McMaster student may hold a key to curbing HIV - a global killer considered one of the worst pandemics in human history.
Sumiti Jain, a PhD student in McMaster researcher Ken Rosenthal’s lab, has successfully identified an optimized a prime-boost vaccine against HIV. Her study presents a strategy that uses an antigen from the glycoprotein spike (or gp41) of the virus, which has proven to prevent HIV infection by blocking and preventing the passage of the disease across the urogenital tract. Importantly, this antigen is highly conserved or shared among HIV strains around the world.
Her study is published in Mucosal Immunology.
"Our work highlights a unique and highly conserved region of HIV, referred to as QARVLAVERY," Jain explains. "Our data indicates that it is an ideal viral region to be included in vaccines to specifically prevent mucosal (sexual) transmission of the virus."
The vaccine design and strategy used in Jain’s study generated HIV-specific antibodies in the blood and mucosal secretions that inhibit HIV infection of target cells and block its passage across mucosal epithelial tissue. "Our results are exciting because QARVLAVERY is the first HIV region to be characterized as mucosally relevant, is highly conserved and generates antibodies that effectively inhibit HIV infection and its passage."
Jain also discovered that mice immunized with this vaccine produce as high levels of IgA antibodies as IgG against this HIV antigen, meaning the development of a prophylactic vaccine could help prevent mucosal HIV infection.
"This in itself is unusual, even more unusual the IgA antibodies appeared before the IgG antibodies," says Rosenthal, a professor in the Department of Pathology and Molecular Medicine and member of the Michael G. DeGroote Institute for Infectious Disease Research. "Importantly, the IgA antibodies generated in the immunized mice were able to neutralize or block infectivity of HIV, and also blocked transcytosis of the virus across human genital epithelial cells. In other words, the antibodies blocked the virus crossing the genital epithelial barrier."
Jain’s results came after years of trial and error, beginning as a 23-year-old graduate student in Rosenthal’s lab, where she tested different antigen regions for vaccine platforms and immunization studies in mice. Her hope was to generate antibodies that protect against HIV infection. "Our greatest challenge was the enormous diversity of HIV-1," she says, "This diversity makes the generation of long-term immunity against it a constantly moving target."
Jain was up to the challenge. "I could not anticipate what the results would be and it was a big risk to take it on. Just coming out of a Bachelor of Science program I had to be as resourceful as possible to acquire the knowledge and skills to meet our objective, address issues along the way, and develop new tools or assays to get to the answers I needed."
Getting results after pursuing several avenues meant that the risk paid off, she says. "They were really exciting results which we did not expect. I remember repeating the assay multiple times in different ways, just to make sure that they were in fact real."
"Sumiti took on an enormous challenge," Rosenthal adds. "The idea was to build on mucosal vaccine and immunization concepts that people had spoken about and there was some data on but people never really pulled it all together. One of the unique parts of Sumiti’s findings is that this antigenic determinant, QARVLAVERY, seems to preferentially induce that IgA which is really novel - people haven’t described that before."
Through further studies, Jain hopes her results will lead to vaccine strategies that could help curb HIV infection via mucosal surfaces. Her future goals involve transitioning into industry where she can push her ideas further and one day make them a reality for those suffering with this disease.
"I thank McMaster for helping me find success early on," Jain says. "Very few labs have the infrastructure, years of knowledge and the resources to pull off studies like this. The great thing about training in Ken’s lab was his willingness to think big and to pursue a project that dug into unexplored concepts and some unknowns. I always believed, even though it may have been naïve, that something novel and beneficial could come out of this work. It was a great feeling to have it all come together in the end."
Ken Rosenthal's website: http://fhs.mcmaster.ca/cgt/rosenthal_ken.html
IIDR home page: http://iidr.mcmaster.ca/index.html
Mucosal Immunology: http://www.nature.com/mi/journal/vaop/ncurrent/full/mi201121a.html