Immunity: a new vaccine strategy successfully induces broad neutralizing antibodies against HIV

December 14, 2019 / Biovalley BIOON / - -- according to the statistics of the United Nations AIDS Program (UNAIDS), about 35 million people around the world have died of the immunodeficiency syndrome (AIDS) caused by HIV infection Today, about 38 million people are living with HIV Antiviral drugs can help people with HIV survive and reduce their ability to transmit the virus to others, but they cannot eliminate the virus infection, so they must be taken for life For a long time, scientists have realized that in order to eliminate HIV as a major public health threat, human beings need a low-cost preventive vaccine for the uninfected However, the rapid mutation rate of HIV and other strategies to avoid immune attack make the design of such vaccines extremely difficult In a new study, researchers from the Scripps Institute and the International AIDS vaccine program (IAVI), a non-profit vaccine research organization, report that their experimental HIV vaccine has reached an important milestone: it can trigger the production of antibodies - the so-called broad neutralizing antibody (bNAb) - against a variety of HIV strains The related research results were recently published in the Journal of immunology The title of the paper is "prevention with glycan modified HIV NFL envelope trimer liposomes elicits broadly neutralizing antibiotics to multiple sites of vulnerability" The corresponding author is Dr Richard Wyatt, Professor of immunology and microbiology, Scripps Institute Picture from immunity, 2019, DOI: 10.1016/j.immunity.2019.10.008 The core of the vaccine design is a virus mimic protein based on HIV Env protein Normally, multiple copies of the shrubby Env protein are scattered on the surface of each spherical HIV particle The molecular structure of each Env protein allows it to bind to a receptor called CD4 located on the surface of immune cells and use this receptor as a portal to invade cells Wyatt and his team have genetically engineered an env version to simulate the important structures existing on the real Env, which is stable enough to be used as a vaccine at the same time To show it in a way similar to real HIV particles, they built virus size synthetic spheres of fat related molecules called "liposomes," which are densely packed with these modified Env proteins On natural HIV Env proteins, sugar related molecules called glycans often help shield all important CD4 binding sites from immune attack As a "starter" vaccine, the researchers used env versions that removed the glycan shield around the CD4 binding site After 48 weeks, the enhanced vaccine uses Env protein carrying the glycan shield to screen the CD4 binding site on Env protein, but also the antibody that can pass through the glycan shield The env protein in the enhanced vaccine injection is also mixed according to different HIV strains, which can generally promote the antibody response against the unchanged env structure in these strains The Wyatt team vaccinated 12 rabbits according to their vaccination strategy and compared the results with those of the control group inoculated only with the env version carrying the glycan shield They found a better response to their vaccine strategy, with five of the rabbits producing antibodies that neutralize a variety of HIV isolates The researchers analyzed the antibodies of a rabbit that reacted most strongly after vaccination and identified two different types of bNAb One of them, bNAb, called E70, blocked the CD4 binding site as expected, but in an unusual way, in part because it seized one of the screened glycan molecules Another bNAb, called 1C2, attacks a different but well-known vulnerable site at the interface between two key parts of the complex protein env The binding of antibody 1C2 obviously destroys the stability of Env so that it can no longer mediate HIV invasion into host cells This shows that the antibody has an extraordinary neutralization range and can block 87% of 208 different HIV isolates Wyatt said this important finding confirms that HIV vaccination in the right way can achieve the goal of inducing bNAb to attack multiple sites on the virus The Wyatt team will continue to test and improve their vaccine strategy in small animal models, and hopes to eventually test it in monkeys and humans (BIOON Com) reference: 1 Viktoriya dubrovskaya et al Prevention with glycan modified HIV NFL envelope trimer liposomes elicits broad neutralising antibiotics to multiple sites of vulnerability Immunity, 2019, doi:10.1016/j.immuni.2019.10.008 2.Experimental HIV vaccine successfully elicits broadly neutralizing antibodies to the virus https://medicalxpress.com/news/2019-11-experimental-hiv-vaccine-successfully-elicits.html