On the eve of the 2017 World AIDS day, the Janssen Vaccines & Prevention Subdivision of Johnson & Johnson Pharmaceutical company, along with the Bill and Melinda Gates Foundation and the National Institutes of Health (NIH), announced the launch of the Imbokodo vaccine trial. The Imbokodo study will test the efficacy of a promising HIV vaccine candidate called the Ad26-env, “mosaic”, vaccine on 2,600 sexually-active women in Southern Africa.
South Africa has one of the largest HIV epidemics in the world. According to 2016 statistics from UNAIDS, a joint United Nations program focused on HIV/AIDS, there were around 135,000 new HIV infections among South Africa’s adolescent girls and young women from age 15 to 29. They also reported that Eastern and Southern Africa accounts for 43% of the global total of new HIV infections (1). These unacceptably high rates of new HIV infections tell us how prominent of a health issue HIV/AIDS is to South Africa. However, HIV/AIDS is not merely a healthcare issue. Young women are the most affected by the HIV/AIDS epidemic because of unprotected rape and domestic violence. The South African government acknowledges the need to address this healthcare crisis not only at a clinical level, but at a sociocultural level.
UNAIDS aims to mobilize worldwide efforts to prevent new HIV infections and provide support for people living with HIV/AIDS. To address the South Africa’s HIV/AIDS crisis, UNAIDS plans to implement platforms for gender equality and human rights that include prevention of gender-based violence, sexual education and prevention methods such as vaccines.
Named after the Zulu term for “rock”, the Imbokodo study references a proverb that celebrates the importance and strength of women in the South Africa community. The Imbokodo study exhibits a way for scientific research to engage with communities in a meaningful way (2).
The Imbokodo study is not the first clinical trial to test the safety and efficacy of the mosaic vaccine. An ongoing smaller-scale study called the APPROACH that began in December of 2014 is testing 400 uninfected individuals in the United States, Rwanda, South Africa, Thailand and Uganda. This study will compare envelope binding responses between the different mosaic vaccine regimens. When infected with HIV, the immune system will induce antibodies that bind to the spikes and the envelope of virus, neutralizing it’s viral activity (3).
So what makes the mosaic vaccine so special?
The primary challenge of developing a vaccine for HIV is it’s viral diversity. According to an article by Dr. Sheri Fink from the International AIDS Vaccine Initiative (IAVI) Report, “Groups from around the world reported finding new HIV recombinant forms in increasing prevalence, particularly among highly-exposed populations or in areas considered epicenters of the HIV pandemic” (4). HIV viral diversity is obtained through various genetic populations allowing the virus to adapt to immune pressures.
In response to the high viral diversity of HIV, researchers have developed the Ad26-env mosaic vaccine which was built upon a previous vaccine prototype named the 2009 HIV Vaccine RV1444, a combination of two vaccines containing gag and env proteins. The RV144 Vaccine Phase 2 HVTN 505 trial evaluated the vaccine developed by the VaxGen biopharmaceutical company on 16,000 participants in Thailand. Results of this study showed that the RV144 vaccine displayed humoral and cellular immunity. It had a modest success rate of 31% preventing the acquisition of HIV. However, this study was still momentous in that it proved that a HIV vaccine is possible, but improvement on the delivery vehicles and optimal antigens for immune response suited for coverage of viral diversity is still needed (5).
More recently in 2017, the Ad26-env mosaic vaccine was released which improved upon the shortcomings of the RV144 vaccine.Conceptually, the mosaic vaccine combines genes from various HIV subtypes. Therefore, the mosaic vaccine is essentially designed to induce an immune response that addresses all of these specific versions HIV viral activity to increase its effectiveness.
The mosaic vaccine will induce the production of three major proteins (Gag, Pol, Env) that are an important part of the HIV viral RNA genome. According to a study by Williamson and Rybicki, the addition of polyprotein Gag, which corresponds to the capsid or core that encapsulates the virus’ genetic makeup, can induce “high-magnitude, broad polyfunctional responses, with memory T-cell responses appropriate for virus control” (6). In response to modified Gag and Pol expression, the combined Gag-Pol polyprotein can provide defense against by inducing the range of responses that allows for the delivery of an immunogen with a larger number of epitopes, the region on the antigen that acts as a binding site for immunoglobulins (7). Another study by Dan Barouch, tested the efficacy of the mosaic vaccine on 72 rhesus monkeys. According to the results, monkey groups receiving the Env protein boosts elicited a substantially higher antibody production than groups receiving only the vector immunizations (5). The insertion of these three particular proteins accounts for the crucial global coverage characteristic of the mosaic vaccine.
Ad26-env vectors contained in the mosaic vaccine will be capable of expressing specific mosaic immunogens that can generate a multifunctional immune response through broadly neutralizing antibodies. In summary, the defining characteristic of the mosaic vaccine is its ability to recognize a wide range of epitopes, increasing the breadth at which the immune system can respond to the virus.
HIV/AIDS continues to be a prevalent and pressing issue. According to Johnson & Johnson, in 2016, an estimated 37 million people were living with HIV-1 globally and 1.8 million people became newly infected with the virus (2).
Although this disease continues to wreak havoc over millions, researchers have made huge strides in the battle against the HIV/AIDS crisis. We hope to see HIV/AIDS as a curable and preventative disease over the course of the several few years. A dual approach of treatment and prevention could be an effective and practical way to approach the HIV pandemic, reducing the rate of transmissions especially those who are at high risk for HIV infections like young women in Sub-saharan Africa. With the aforementioned initiatives and increasing prominence of the mosaic vaccine, developing a global preventative vaccine could be the key to putting an end to the HIV/AIDS pandemic and protecting high-risk populations from the possibility of new infections.
Edited by: Chase Breimeier
Illustrated by: Caroline Cao