An Adjuvant That Increases Protective Antibody Responses to Polysaccharide Antigens and Enables Recall Responses

Abstract

Protection against encapsulated bacteria can be elicited using polysaccharide vaccines. These antigens often behave as T-cell-independent type 2 antigens (TI-2 Ags). However, TI-2 Ags, including pneumococcal polysaccharides, often elicit weak immunoglobulin G (IgG) responses and are refractive to boosting. Conjugate vaccines have not completely overcome this challenge and hence, alternative strategies are required to enhance polysaccharide vaccine responses. Herein, we describe an adjuvant consisting of a Toll-like receptor and C-type lectin receptor agonist pairing that significantly increases primary immunoglobulin M and IgG responses to TI-2 Ags as well as enables significant boosting when coadministered with polysaccharide vaccines. Consistent with this, the adjuvant significantly increased the generation of both TI-2 memory B cells and long-lived antibody secreting cells. Adjuvant effects were highly dependent on B-cell-intrinsic MyD88, but not Trif expression. Importantly, coadministration of the adjuvant with the Pneumovax vaccine significantly increased the protective efficacy of vaccination in a lethal challenge mouse model of pneumococcal respiratory infection. Collectively, these data provide evidence that B-cell-directed adjuvants have promise in significantly improving the quality and quantity of serologic and B-cell memory responses to clinically relevant polysaccharide vaccines.

Influence of immune aging on vaccine responses

“…In addition, the use of PCV13 (currently recommended in multiple European countries), which in theory should elicit higher T-cell responses and better mucosal immunity, only showed 65% efficacy in adults aged 65 years and rapidly dropped to 40% in adults aged 75 years. 84,85 Thus, there is significant room for improved understanding of polysaccharide-based immunity, vaccine design, such as the addition of adjuvants, 86 and age.…”

An Overview of Nanocarrier-Based Adjuvants for Vaccine Delivery

“…Similarly, Phipps et al formulated TLR and CLR agonist pairing adjuvant and co-administered with Pneumovax vaccine. The vaccine combination significantly elevated T-cell independent type-2 antigens and also improved protective efficacy in pneumococcal respiratory infection mouse models [ 166 ]. Recently, researchers examined the crosstalk of miR-511-3p, encoded within the human MRC1 gene, and CLRs on DCs.…”

B Cell Subsets Differentially Contribute to the T Cell–Independent Memory Pool

“…Mice were immunized with 1 or 25 mg NP 40 -AECM-Ficoll or TNP 65 -AECM-Ficoll (Biosearch Technologies) in 200 ml PBS i.p. NP-specific ELISAs were performed as previously described (13). To approximate serum concentrations of NP-specific isotypes, we used standards consisting of NP-specific IgM a and IgG mAbs produced in-house from hybridomas generated from NP 40 -Ficoll-immunized V H B1-8 Tg mice.…”

“…In adults, pneumococcal polysaccharide conjugate vaccines do not boost as well, and overall Ab responses have been reported to be similar to those elicited to native pneumococcal polysaccharides (12). Thus, alternative approaches to enhancing these vaccine responses, such as use of B cell-activating adjuvants (13), may be needed to improve TI-2 Ag-specific memory B cell formation and responsiveness to secondary Ag encounter.…”