Nanoparticle Vaccines Adopting Virus-like Features for Enhanced Immune Potentiation

Chattopadhyay, Saborni; Chen, Jui-Yi; Chen, Hui-Wen; Hu, Che-Ming Jack

Besides incorporating antigens and adjuvants on the same particle for co-delivery, a number of studies demonstrated that delivering antigen and adjuvant in separate but similar nanocarriers can also elevate antigen-specific immune responses. In one example, an HIV antigen (HIVgp41) was anchored on the surface of liposomes and co-delivered with a liposomal formulation of cd-GMP, a potent agonist of the STING pathway. The study showed a substantial accumulation of the STING agonist in draining lymph nodes [165] , and it is expected that the liposome-bound peptide antigen was delivered in a similar fashion. As a result, enhanced activation of antigen presenting cells and increased levels of antibodies against the HIV antigen were observed. Immune stimulation by formulations containing separate antigen-and adjuvant-loaded nanoparticles was also reported in a study exploring the benefit of multi-adjuvant loaded particles. By incorporating multiple distinctive activators of TLRs, including monophosphoryl lipid A (a TLR4 agonist) and R837 (a TLR7 agonist), Kasturi et al. demonstrated adjuvant synergism that triggered elevated antigen-specific humoral responses [70] . Using ovalbumin and hemagglutinin of influenza viruses, the investigators demonstrated long-lasting humoral responses and evidence of memory B cell formation following immunization with the nanoparticle vaccine. These examples highlight the functional versatility of synthetic nanoparticles, which can facilitate different modes of virus mimicry for immune activation.