Combinatorial use of TLR4 and TLR7 ligands in virus-like-particles (VLPs) as potent adjuvants for prophylactic and therapeutic vaccines.
- Able to elicit both cellular and humoral immunity.
- Synergistically improves the quality of B- and T-cell responses.
- Induces long-lived and persistent antigen-specific immune responses.
Traditional vaccines normally consist of attenuated or dead microbes, or their fragments. Many of them lack sufficient immunogenicity and require adjuvants, sometimes multiple booster injections to increase their efficacy, such as those for Hepatitis A, Hepatitis B, HPV, Pneumococcus infection, etc. Newer vaccine candidates for either prophylactic or therapeutic purposes are mainly based on protective antigens, which are inherently less immunogenic than the traditional ones making adjuvant indispensable. Therefore, improved adjuvants are of central importance in both maximizing potency of current vaccines and developing novel vaccines.
Emory researchers have developed a vaccine adjuvant using combined TLR4 and TLR7 ligands. Simultaneous administration of TLR4 and TLR7 agonists via VLPs enables the rapid activation of both cellular and humoral immune responses. More importantly, the responses are long-lived and persistent, thereby tackling the most striking challenge in vaccine adjuvant development. Compared to single ligand, a dual TLR stimuli strategy enhances the generation of memory B-cells and dramatically improves the quality of induced antibodies in terms of both absolute numbers and avidity. In addition, combined TLR ligands can further augment vaccine efficacy by stimulating effector CD8+ T cells and increasing production of pro-inflammatory cytokines in a synergistic manner. This technology provides a universal platform for vaccine design against infection and potentially tumors as well.
In vivo tests against lethal avian and swine influenza on mice and H1N1 influenza on rhesus macaques have been conducted.