Preclinical studies have shown that the induction of secretory IgA (sIgA) in mucosa and neutralizing antibodies (NAbs) in sera is essential for designing vaccines that can effectively block the transmission of HIV-1. We previously showed that a vaccine consisting of bacterium-like particles (BLPs) displaying Protan-gp120AE-MTQ (PAM) could induce mucosal immune responses through intranasal (IN) immunization in mice and NAbs through intramuscular (IM) immunization in guinea pigs. Here, we evaluated the ability of this vaccine BLP-PAM to elicit HIV-1specific mucosal and systemic immune responses through IN and IM immunization combination strategies in rhesus macaques. First, the morphology, antigenicity and epitope accessibility of the vaccine were analysed by transmission electron microscopy, biolayer interferometry and ELISA. In BLP-PAMimmunized macaques, HIV-1-specific sIgA were rapidly induced through IN immunization in situ and distant mucosal sites, although the immune responses are relatively weak. Furthermore, the HIV-1-specific IgG and IgA antibody levels in mucosal secretions were enhanced and maintained, while production of serum NAbs against heterologous HIV-1 tier 1 and 2 pseudoviruses was elicited after IM boost. Additionally, situ mucosal responses and systemic T cell immune responses were improved by rAd2-gp120AE boost immunization via the IN and IM routes. These results suggested that BLP-based delivery in combination with the IN and IM immunization approach represents a potential vaccine strategy against HIV-1.
Infection diseases such as AIDS and COVID-19 remain challenging in regard to protective vaccine design, while adjuvants are critical for subunit vaccines to induce strong, broad, and durable immune responses against variable pathogens. Here, we demonstrate that periodic mesoporous organosilica (PMO) acts as a multifunctional nanoadjuvant by adsorbing recombinant protein antigens. It can effectively deliver antigens to lymph nodes (LNs), prolong antigen exposure, and rapidly elicit germinal center (GC) responses by directly activating naive B cells via the C-type lectin receptor signaling pathway. In mice, both the gp120 trimer (HIV-1 antigen) and the receptor-binding domain (SARS-CoV-2 antigen) with the PMO nanoadjuvant elicit potent and durable antibodies that neutralize heterologous virus strains. LN immune cells analysis shows that PMO helps to effectively activate the T-follicular helper cells, GC B cells, and memory B cells and eventually develop broad and durable humoral responses. Moreover, the PMO nanoadjuvant elicits a strong cellular immune response and shapes this immune response by eliciting high levels of effector T helper cell cytokines. This study identifies a promising nanoadjuvant for subunit vaccines against multiple pathogens.
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