Mice and macaques pave the way for effective HIV vaccines

There is encouraging news this week on the prospects for an effective vaccine against HIV. A  research team led by Professor Mariano Esteban at the Spanish Superior Scientific Research Council (CSIC) have announced that the vaccine MVA-B elicited a persistent immune response against HIV in  85% of volunteers in a phase 1 clinical trial. MVA-B is a therapeutic vaccine, it is not intended to block infection but rather to keep HIV levels in the body at levels well below those at which the virus can cause illness.

As a CSIC press release published online on EureakAlert! notes the MVA-B vaccine, created by inserting four HIV genes from the B subtype of HIV – the subtype accounting for most HIV infections in Europe and North America – into a vector derived from the Modified Ankara Vaccinia virus (a smallpox vaccine and shown to be safe in both animal studies and extensive human use), notes that:

In 2008, MVA-B already showed very high efficiency in mice as well as macaque monkeys against Simian’s immunodeficiency virus (SIV). Due to it’s high immunological response in humans, Phase I clinic trials will be conducted with HIV infected volunteers, to test its efficiency as a therapeutic vaccine.”

This is indeed true, a 2007 study in mice revealed that the MVA-B vaccine induced a strong immune response , while a paper published in 2008 by the same group demonstrated that a very similar MVA vaccine was able to induce a robust response involving both the HIV-1-specific CD4⁺ helper T-cells  and CD8⁺ cytotoxic T cells in Rhesus macaques, and was able to control virus levels in macaques infected with the SHIV 89.6P hybrid virus whereas in unvaccinated monkeys the levels of virus rose and most developed an AIDS-like illness.

There is a question over whether the immune response generated by the MVA-B vaccine will be able to restrict HIV in humans, after all the MRK-Ad5 vaccine which failed to restrict the HIV virus in human trials and the pathogenic SIV MAC239 – considered a better model for HIV infection than SHIV 89.6p – in macaque monkeys had successfully controlled SHIV 89.6P in earlier studies.

Some reassurance on this issue comes from a study at Oregon Health and Science University (OHSU) that was announced earlier this year, where a group led by Dr. Louis Picker used a different vaccine vector – one based on Cytomegalovirus – to elicit a very similar broad immune response , with strong memory T-cell involvement, to that induced by MVA-B, and found that it induced long-term control the highly pathogenic SIV MAC239 strain. This was the highest degree of control demonstrated to date against this SIV strain, and indeed the cytomegalovirus vaccine is one of the first to demonstrate any ability to control SIV MAC239 levels.

Professor Esteban and his colleagues are certainly not resting on their laurels either, further clinical trials of the MVA-B vaccine are planned, to determine whether it can protect against HIV.  In the meantime they are also seeking to improve on this vaccine.  Earlier this year they published a paper in the open-access journal PloS One where they deleted a gene in the MVA vector to yield a new MVA-B  vaccine that showed in mice a substantial increase in the magnitude and breath of the immune response compared with their original MVA-B vaccine, and an even better  memory T-cell response. They now plan to evaluate this improved vaccine in a non-human primate model of HIV infection, and it will be interesting to see if they choose to use a more stringent model of infection such as SIV MAC239 rather than SHIV-89.6P.

Despite the setbacks and disappointments over the past two decades, it is clear from the work being done at the CSIC and OHSU that real progress is being made towards the development of both prophylactic and therapeutic  vaccines against HIV, and it is just as clear that animal research continues to play a vital role in that progress.

Paul Browne