Improvement of antibody responses by HIV envelope DNA and protein co-immunization

Abstract

Background Developing HIV Envelope (Env) vaccine components that elicit durable and protective antibody responses is an urgent priority, given the results from the RV144 trial. Optimization of both the immunogens and vaccination strategies will be needed to generate potent, durable antibodies. Due to the diversity of HIV, an effective Env-based vaccine will most likely require an extensive coverage of antigenic variants. A vaccine co-delivering Env immunogens as DNA and protein components could provide such coverage. Here, we examine a DNA and protein co-immunization strategy by characterizing the antibody responses and evaluating the relative contribution of each vaccine component. Method We co-immunized rabbits with representative subtype A or B HIV gp160 plasmid DNA plus Env gp140 trimeric glycoprotein and compared the responses to those obtained with either glycoprotein alone or glycoprotein in combination with empty vector. Results DNA and glycoprotein co-immunization was superior to immunization with glycoprotein alone by enhancing antibody kinetics, magnitude, avidity, and neutralizing potency. Importantly, the empty DNA vector did not contribute to these responses. Humoral responses elicited by mismatched DNA and protein components were comparable or higher than the responses produced by the matched vaccines. Conclusion Our data show that co-delivering DNA and protein can augment antibodies to Env. The rate and magnitude of immune responses suggest that this approach has the potential to streamline vaccine regimens by inducing higher antibody responses using fewer vaccinations, an advantage for a successful HIV vaccine design.

Envelope Variants Circulating as Initial Neutralization Breadth Developed in Two HIV-Infected Subjects Stimulate Multiclade Neutralizing Antibodies in Rabbits

“…(i) SPR. Antibody concentrations in rabbit sera and in human plasma to autologous trimeric gp140 proteins 014_092603_G4 and 014_080406-C4a and to heterolo-gous trimer SF612 were determined on a Biacore T200 instrument (GE Healthcare, Piscataway, NJ) as previously described (50).…”

“…Longitudinal plasma samples were tested for neutralization of four clade B heterologous viruses, one clade A heterologous virus, and two clade C heterologous viruses in a TZM-bl assay. Neutralization data are expressed as ID 50 , the plasma dilution that neutralized 50% of the infecting virus. Neutralization breadth scores were determined as previously described (72).…”

“…We expanded this approach to using immunogens from a subtype A-infected human subject, using a bioinformatic approach to select vaccine clones that recapitulate the evolution of quasispecies variants (48). Moreover, we also showed that coimmunization with Env-expressing plasmid DNA and recombinant Env proteins more effectively generated Env-specific antibodies in rabbits (49,50) and CD8 T cell responses in mice (49). In the current study, we built upon these recent findings and used longitudinally cloned quasispecies gp160 env genes isolated from plasma from two subjects (VC10014 and VC20013).…”

How can Improve DNA Vaccine Modalities as a Therapeutic Approach against HIV Infections?

“…These data showed that co-delivering DNA and protein can increase antibody responses to Env. Hence, this approach has the potential to simplify vaccine regimens by inducing higher antibody responses using fewer vaccinations, an advantage for a successful HIV vaccine design [57].…”

“…Due to the diversity of HIV, an effective viral envelop (Env)-based vaccine will likely need a broad coverage of antigenic variants. A vaccine codelivering Env immunogens as DNA and protein components could provide such coverage [14]. This review is focused on optimization of DNA-based vaccines using different strategies against HIV infections.…”