Vaccine and Infectious Disease Division

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Optimizing the benefits from HIV vaccines

One hurdle in HIV vaccine development is because genetically distinguishable strains (clades) of HIV circulate in different areas of the globe. At present, the HIV vaccine field is largely devoted to the development of clade specific vaccines for sub-Saharan Africa (clade C matched) and clade B matched vaccines for the US and Europe; excluding many regions of the world where alternate clade types exist. This process slows the pace of vaccine research and potential licensure. For example, it has taken 5 years to manufacture a clade C vaccine based on the partially efficacious clade B vaccine used in the Thai Trial; testing takes another 5 years. As such, it is a 10 year process to move forward in evaluating one vaccine to another. Lives are lost and resources are consumed during this time period.

A recent article from VIDD scientists demonstrates the need for a paradigm shift in thinking about HIV vaccine development: that the development of region specific (clade matched) vaccines is not the best approach for reducing HIV prevalence over time. VIDD Senior Staff Scientist Dr. Dobromir Dimitrov, Principal Staff Scientist Dr. Jim Kublin and Member Dr. Larry Corey, with PHS Division Member Dr. Scott Ramsey, used mathematical models to investigate the implementation of non-clade matched and clade specific vaccines by simulating the HIV epidemic in San Francisco and South Africa: two regions of the world where the epidemic is well characterized. They evaluated three strategies: 1) Immediate Strategy (non-matched vaccine with 20-40% efficacy introduced immediately and used for 30 years; 2) Delayed Strategy (matched vaccine with 50% efficacy introduced when it is available); and 3) Replacement Strategy (original non-matched vaccine introduced immediately followed by the matched vaccine when it is available). In both San Francisco and South Africa, the implementation of a non-clade matched vaccine even with reduced efficacy (Immediate) offered greater benefit than constructing, manufacturing and testing a clade matched vaccine that had somewhat higher efficacy (Delayed) (see figure). In addition, the most effective 10-year vaccination strategy was to employ non-clade matched vaccines immediately followed by the rapid development of a more effective clade matched vaccine; suggesting this would be an effective public health strategy for reducing HIV infection in high risk populations.

Immediate Strategy offers greater benefit than Delayed Strategy

Time needed (break even time) for a 50% effective clade-specific vaccine introduced in South Africa (left) and San Francisco (right) after a development delay of 1 to 10 years to surpass a 20-40% effective non-matched vaccine introduced immediately in number of new infections prevented. Mean projections generated by 1,000 epidemic settings representative of the HIV epidemic in South Africa and San Francisco.

Adapted from Dimitrov, et al.

 


Dobromir Dimitrov, James G. Kublin, Scott Ramsey, and Lawrence Corey. Are Clade Specific HIV Vaccines a Necessity? An Analysis Based on Mathematical Models. EBioMedicine. Available online 5 November 2015.
 

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