Adjuvant & Antigen Research
The primary mission of the Department of Adjuvant and Antigen Research is to discover, formulate, and deploy vaccine formulations that include safe, potent, inexpensive, and clinically acceptable adjuvants, antigens, and vaccine strategies for induction of multi-clade protection against HIV-1.
- The department has more than 20 years of experience with numerous adjuvants and antigens for human vaccines, including lipids, liposomes, lipid emulsions, many generic adjuvants, and peptide and protein antigens.
- Research focuses on immunization to induce broadly neutralizing antibodies, cell-mediated immunity, and mucosal immunity to HIV-1.
- Transcutaneous immunization (TCI) with adjuvants and antigens was originally invented at WRAIR by departmental personnel. The patented TCI technology has been licensed to Intercell, A.G. where it is in phase III testing for a traveler’s diarrhea vaccine. TCI continues to be an important departmental research strategy involving needle-free immunization to induce humoral, cellular, and mucosal immunity to HIV-1.
Current Research
- Liposomes containing lipid A and HIV-1 protein or peptide antigen are being used as immunogens to induce neutralizing “multispecific” antibodies in which the antigen binding site of the antibody simultaneously binds both to the immunizing lipid and protein.
- Pathological effects of p24 of HIV-1 on antigen processing by antigen presenting cells are being examined, and how these effects can be overcome by adjuvanted liposomes containing lipid A.
- The suitability of numerous adjuvants is being examined for vaccine formulations either to HIV-1 or to anthrax. Comparative adjuvant studies with anthrax antigen are in progress in non-human primates to identify safe, non-reactogenic, easily manufactured, and protective adjuvant formulations that induce enhanced titers of neutralizing antibodies.
Highlights & Publications
- Immunization of mice with liposomes containing lipid A and both a peptide antigen from HIV-1 gp41, and a lipid antigen, induced neutralizing monoclonal “multispecific” antibodies that emulated the lipid and protein binding characteristics of the broadly neutralizing human monoclonal antibodies known as 2F5 and 4E10. (download article)
- Demonstrated that p24 down-regulates immunoproteasome subunits of murine dendritic cells, and that the effects were reversed by adjuvanted liposomes containing lipid A. (download article)
- By immunization of mice with liposomes containing lipid A and p24 antigen, we induced effector CD4+ T-cells, memory CD8+ T-cells, and pro-inflammatory cytokines.
- We have discovered that normal human erythrocytes selectively adsorb infectious (as opposed to non-infectious or degraded) HIV-1 particles, and the adsorbed particles are fully available for trans infection of CD4(+) cells (download article http://dx.plos.org/10.1371/journal.pone.0008297)
- Selected publications