DNA-prime/protein-boost approach
Dr. Shan Lu was one of the pioneers of the use of DNA to elicit protective immune responses (Fynan, 2018). His laboratory later demonstrated that naked DNA is excellent at priming CD4+ T cells and B cells to respond to subsequent boosts with matching recombinant proteins, resulting in high titers of antibodies to HIV (Chen, 2014). The heterologous prime/boost approach is the state of the art in the HIV vaccine field (Lu,2009) and is the only approach that demonstrated partial efficacy in prevention of HIV infection in the 2010 RV144 trial in Thailand (Rerks-Ngarm, 2009).
WHV’s vaccine platform is based on three main concepts researched and developed at Dr. Shan Lu’s Laboratory of Nucleic Acid Vaccines at the UMMS: polyvalency of immunogens, DNA-prime/protein boost, and matching prime/boost immunogens.
Polyvalency of immunogens
To combat the tremendous diversity of HIV, WHV’s vaccine candidate uses the classical polyvalent vaccine approach in which multiple variants of the virus are combined to elicit cross-protective immune responses. The polyvalent approach has been used to develop vaccines against pathogens that have multiple circulating strains or high genetic diversity, including poliovirus, human papilloma virus (HPV), influenza, and pneumococcus.
“Polyvalency has been arguably more useful than using conserved immunogens to target multiple serotypes” (Schlingmann, 2018)
DNA-prime/protein-boost
Over the years, data from Dr. Shan Lu’s laboratory and others clearly demonstrated the value of DNA priming for inducing high levels of antibodies to recombinant proteins. Neither DNA nor protein on their own result in high antibody titers, but a combination of the two results in potent and balanced antibody response. For more information, visit Preclinical Studies and Clinical Trials.
Matching prime/boost immunogens
A heterologous prime-boost is the state of the art in the HIV vaccine field. However, most of the past heterologous prime-boost studies and clinical trials used prime and boost immunogens that were derived from different viral strains. Our data show that in order to take full advantage of the primed immune response, the DNA and the protein components of the vaccine need to be matched (derived from the same strain). Matching immunogens lead to improved T-cell help and stimulate maturation of the full set of B-cell specificities elicited at the priming stage.
Selection of gp120 immunogens
The first generation of the vaccine used in the DP6-001 trial was developed in the mid-90s and included envelopes from the small number of viral variants available at the time. For the second generation formulation used in the HVTN 124 trial, a large panel of more than 60 gp120 immunogens from primary isolates was tested for immunogenicity in rabbits and the best variants for each clade were chosen to be included in the vaccine (Wang, 2017).
