It is true that HIV/AIDS has had a tumultuous history of biomedical research in hopes of treatment and prevention. While the development of drugs which treat the pandemic, such as antiretroviral drugs, has been quite successful, vaccine development has been marred by shortfalls. Vaccine research has been largely characterized by hopeful vaccine candidates and their failed translation into drugs for human application. The promise of a successful HIV/AIDS vaccine is certainly nothing new.
However, in May, another glimmer of hope has emerged. Studies were published reporting that another breakthrough may have been discovered. A team of researchers at the Oregon Health & Science University conducted a ten-year study with macaque monkeys by giving a cytomegalovirus vaccine (CMV) to twenty-four test subjects for the simian immuno-deficiency virus (SIV), the primate viral agent that HIV evolved from. CMV is part of the herpesviridae family of viruses, the very same that causes the herpes simplex virus.
The optimism of the results of the CMV tests stems from some unprecedented outcomes. Upon exposure to SIV, thirteen of the monkeys had protection against the virus. Twelve of those monkeys were able to retain this immunity a year after the vaccine was administered. The vaccine was able to eliminate all traces of SIV from the monkeys. The Chief Operating Officer of the International AIDS Vaccine Initiative (IAVI), David Cook, characterized the findings to yield “the most profound protection we’ve seen in an experimental vaccine.”
The drug differs from other vaccines based on the vector that the team employed, CMV, to stimulate an immuno-response. The lead researcher on the Oregon team, Dr. Louis Picker, attributes the success of the vaccine in the macaques to the nature of the vector: “it fools the body into thinking it’s always under threat, and keeps the soldiers ready at the point where…the [SIV] virus comes into the body.” By cutting off the SIV’s access to the host monkey’s cell machinery to replicate through early recognition, the vaccine was able to eradicate the SIV before it progressed to disease.
The largest problem with this breakthrough: it is for a different virus. While HIV is a strain derived from SIV, the fact remains that their research targeted a dissimilar virus. Lawrence Corey, a medical virologist, recognizes that while the success is promising “there is little corollary between animal and human models for HIV; killing the virus in a laboratory or animal host does not guarantee success in humans.” Another large issue with tackling HIV is its ability to high mutability and its ability to evade a host’s immuno-defense until it infects cells and replicates. In past vaccine attempts, the vector used in the vaccine was unable to account for this adaptability and evasiveness of the virus and therefore proved ineffective in fostering herd immunity among populations.
A great deal more laboratory work needs to be conducted by the team in order to research how to take what they have achieved in simians and adapt it to humans. It will be critical that this design of a HIV-CMV vaccine include intensive studies on numerous factors and variables, including the drug’s effectiveness over time and in different contexts, the drug’s safety with respect to the vector, its side effects, and interaction with other drugs and diseases. Despite this, a deeper understanding of the virus from further research and experimentation with CMV may ultimately serve as an important component to an actual vaccine.
The severity of the prevalence of AIDS renders any breakthrough in vaccine research a significant one, especially considering the vulnerability of African populations to the virus . The greatest concern about CMV as a vector is the troubling epidemiology among vulnerable populations, such as children, pregnant women, and immuno-compromised individuals. It is estimated by researchers that over ninety-eight percent of the population in Africa is infected by a dormant CMV virus. While this agent is endemic and can stay benign for many years (such as the related herpes virus), it has been known to be fatal to these vulnerable groups, especially the immuno-compromised, like HIV-infected patients. CMV has been known to be the root of immuno-surpression over the human life-course, andis additionally recognized as one of the biggest causes of birth defects in the developing world. If CMV is the vector that is used to deliver the vaccine, mutations or simply failures of the drug in these populations will not only negate drug action, but will also induce the pathogenesis of CMV. These issues are the challenges that researchers will have to overcome during the continuing research for an HIV vaccine.
While the recent reports of the effectiveness of CMV-based vaccine in preventing SIV are encouraging given the impressive medical outcomes through research, it is important to temper expectations and optimism in the face of this news. Countless reports and studies have been published in favor of a spectrum of vaccine candidates – yet none have emerged to be an appropriate antidote. Furthermore, adapting this CMV vaccine to HIV in humans will require another intensive research process. Given the complexity of the viral agent and the nature of the mechanism by which it causes disease in humans, this phase of drug development will not be short or simple. Will the studies done with CMV on macaques ultimately lead to a successful HIV vaccine or will it simply serve as a stepping stone for further research by broadening our understanding of HIV and its relatives? Only time will tell as the quest towards a cure marches on.
Photos: US Mission Geneva, SimplyAvoir (flickr)