MUCOVAC2

A team from Imperial College, Hull York Medical School, Medical Research Council Clinical Trial Unit and Infectious Disease Research Institute in London is carrying out what they claim is the first clinical trial of an injectable vaccine for HIV which causes AIDS. They are also evaluating whether the vaccine is safe for use in human volunteers. We take this opportunity to understand the issues, problems and approach for HIV Vaccines:

Is there any Vaccine available against HIV/AIDS currently?

» NO. Currently, there is no effective vaccine against HIV, the virus that causes AIDS. The current strategies to combat the disease includes the highly active antiretroviral therapy (HAART) and social approaches such as safe sex prevention and awareness campaigns. HAART allows the stabilization of the patient’s symptoms and viremia, but they do not cure the patient of HIV, nor of the symptoms of AIDS. HAART also can not stop the spread of the disease from those who are HIV+ to those who are not.

Why developing an HIV Vaccine has been a difficult job?

» The classical vaccination approach has failed to recognize the viral envelope proteins in the case of HIV-1.

» Classic vaccines mimic natural immunity against reinfection generally seen in individuals recovered from infection; there are almost no recovered AIDS patients.

» Most vaccines protect against disease, not against infection; HIV infection may remain latent for long periods before causing AIDS.

» Most effective vaccines are whole-killed or live-attenuated organisms; killed HIV-1 does not retain antigenicity and the use of a live retrovirus vaccine raises safety issues.

» Most vaccines protect against infections that are infrequently encountered; HIV may be encountered daily by individuals at high risk.

» Most vaccines protect against infections through mucosal surfaces of the respiratory or gastrointestinal tract; the great majority of HIV infection is through the genital tract.

What are biggest threats for development of HIV Vaccine?

» First, HIV is highly mutable. Because of the virus’ ability to rapidly respond to selective pressures imposed by the immune system, the population of virus in an infected individual typically evolves so that it can evade the two major arms of the adaptive immune system; humoral (antibody-mediated) and cellular (mediated by T cells) immunity.

» Second, HIV isolates are themselves highly variable. HIV can be categorized into multiple clades and subtypes with a high degree of genetic divergence. Therefore, the immune responses raised by any vaccine need to be broad enough to account for this variability. Any vaccine that lacks this breadth is unlikely to be effective.

What is the approach of the London scientists who are carrying out the trials?

The vaccine which is being tested contains trimeric HIV envelope protein (gp140) which can target the virus’ most virulent strain "Clade C" that has caused the greatest number of HIV infections around the globe, infecting half of the 34 million people with HIV. The trial has been named MUCOVAC2.

MUCOVAC2 is evaluating a vaccine that contains the HIV trimeric gp140 protein CN54, representative of Clade C strains of the virus. This clade of HIV is the most prevalent type of virus in Sub-Saharan Africa and responsible for the greatest number of infections globally. The trimeric protein represents the major target for antibodies on the viral surface. The vaccine candidate will be formulated with an adjuvant — GLA — developed to enhance immune responsiveness following intramuscular injection. GLA formulations have been previously tested clinically with promising results. The scientists have enrolled 36 healthy, HIV-negative women aged 18-45 years at St George’s University of London and the HYMS Experimental Medicine Unit at York Hospital. (Inputs: Times of India, PTI and Wikipedia)