A particulate saponin/TLR agonist vaccine adjuvant alters lymph flow and modulates adaptive immunity

Abstract

An adjuvant composed of saponin and a TLR4 agonist acts by enhancing lymph flow and antigen entry into lymph nodes.

A Lymph Node Targeted Adjuvant and Engineered Subunit Vaccine Promotes Potent Immunity to Epstein-Barr Virus in HLA-expressing Mice

“…These trends were most notable in relation to EBVpoly, which was minimally present in draining lymph nodes when administered with soluble CpG. These changes in antigen biodistribution are consistent with past studies observing adjuvant-driven mechanisms for improving lymph node accumulation of co-administered protein antigens; for example (i) local recruitment, antigen acquisition, and lymphatic transit of phagocytes, (ii) enhancement of afferent lymph ow, and (iii) optimization of antigen capture by lymph node resident innate immune cells have been previously reported 28,44,45 . These mechanisms may be promoted by AMP-CpG given the signi cant improvement in EBVpoly accumulation to draining lymph nodes associated with AMP-CpG relative to soluble CpG comparators.…”

“…Transit of molecules to the lymph nodes from a peripheral injection site is known to correlate with molecular size 22,23 and the e ciency of lymphatic drainage can be further modulated in response to local adjuvant-mediated in ammatory activity 28 . To investigate the e ciency of lymph node accumulation of EBVpoly and gp350, we administered uorescently labeled proteins in mice together with soluble CpG or AMP-CpG and analyzed tissue-associated uorescent signal in whole lymph nodes by IVIS imaging.…”

Highly mutated antibodies capable of neutralizing N276 glycan-deficient HIV after a single immunization with an Env trimer

“…Although our observations were made in the context of a closely controlled mouse model, one shepherding approach may be to maximize B GC affinity maturation from each immunization instead of administering frequent boosts with numerous immunogens. Notably, impressive SHMs were achievable without employing recently described optimized Cell Reports 38, 110485, March 8, 2022 11 Article ll OPEN ACCESS vaccination strategies (Cirelli et al, 2019;Dubrovskaya et al, 2019;Moyer et al, 2020;Tokatlian et al, 2019) and new adjuvants (Alving et al, 2012;Kasturi et al, 2020;Silva et al, 2021). It may be possible to give rise to breadth-inducing mutations with fewer boosts, and introducing Env trimer-based boost immunogens earlier could be a desirable strategy for doing so.…”

Adjuvants influence the maturation of VRC01-like antibodies during immunization

“…Adjuvants alter the magnitude as well as the quality of the immune response (79)(80)(81). However, the effect of adjuvant on the selection, expansion, and maturation of VRC01 B cell subclasses…”

“…Adjuvants alter the magnitude as well as the quality of the immune response ( 79-81 ). However, the effect of adjuvant on the selection, expansion, and maturation of VRC01 B cell subclasses has not yet been investigated in detail, although there are some reports suggesting that different adjuvants may select for different HC/LC amino acids ( 76 ).…”