Human lymphoid tissue sampling for vaccinology

Abstract

Long-lived plasma cells (LLPCs) – largely resident in the bone marrow – secrete antibody over months and years, thus maintaining serum antibody concentrations relevant for vaccine-mediated immunity. Little is known regarding factors that can modulate the induction of human LLPC responses in draining lymph node germinal centres, or those that maintain LLPCs in bone marrow niches following vaccination. Here, we review human and non-human primate vaccination studies which incorporate draining lymph node and/or bone marrow aspirate sampling. We emphasise the key contributions these samples can make to improve our understanding of LLPC immunology and guide rational vaccine development. Specifically, we highlight findings related to the impact of vaccine dosing regimens, adjuvant/vaccine platform selection, duration of germinal centre reactions in draining lymph nodes and relevance for timing of tissue sampling, and heterogeneity in bone marrow plasma cell populations. Much of this work has come from recent studies with SARS-CoV-2 vaccine candidates or, with respect to the non-human primate work, HIV vaccine development.

Analyses of human vaccine-specific circulating and bone marrow-resident B cell populations reveal benefit of delayed vaccine booster dosing with blood-stage malaria antigens

“…While bone marrow aspirates were not taken in the DBPRII clinical trials, we had the rare opportunity to investigate bone marrow plasma cells with the RH5.1/Matrix-M™ adult vaccinees – the first bone marrow analyses in the context of malaria vaccination ( 13 ). Here, we observed a trend to higher frequencies of RH5-specific cells within total bone marrow B cells in the protein/adjuvant delayed dosing regimen ( Figure 6A ), which correlated strongly with matched time point serum anti-RH5 IgG ( Figure 6B ).…”

Analyses of vaccine-specific circulating and bone marrow-resident B cell populations reveal benefit of delayed vaccine booster dosing with blood-stage malaria antigens

“…While bone marrow aspirates were not taken in the DBPRII clinical trials, we had the rare opportunity to investigate bone marrow plasma cells with the RH5.1/Matrix-M™ adult vaccinees – the first bone marrow analyses in the context of malaria vaccination [13]. Here, we observed a trend to higher frequencies of RH5-specific cells within total bone marrow B cells in the delayed dosing regimen ( Figure 6A ) which correlated strongly with matched time point serum anti-RH5 IgG ( Figure 6B ).…”

“…Significant post-vaccination responses were observed within DBPRII "Population 1" and RH5 "Population 12", which appear to be subsets of the resting memory populations. tissue sampling (reviewed in [13]) and, to the best of our knowledge, this trial represents the first direct analysis of human bone marrow-resident plasma cells in the context of malaria.…”

“…Indeed, of great interest is the strong correlation detected between circulating serum IgG or memory B cells and vaccine-specific bone marrow plasma cells in the RH5 trial. Very few vaccine studies have included lymphoid tissue sampling (reviewed in [13]) and, to the best of our knowledge, this trial represents the first direct analysis of human bone marrow-resident plasma cells in the context of malaria. Since long-term serum antibody is maintained through secretion by long-lived plasma cells in the bone marrow, understanding the factors that impact this compartment is central to optimising durability of humoral immunity.…”

“…Here, higher IFNγ responses were observed with the viral vector platform; no significant responses were observed within the protein/adjuvant platform (Supplemental Figure 9). Bone marrow plasma cells correlate with serum antibody and circulating memory B cells in adult RH5.1/Matrix-M TM vaccinees While bone marrow aspirates were not taken in the DBPRII clinical trials, we had the rare opportunity to investigate bone marrow plasma cells with the RH5.1/Matrix-M TM adult vaccinees -the first bone marrow analyses in the context of malaria vaccination [13]. Here, we observed a trend to higher frequencies of RH5-specific cells within total bone marrow B cells in the delayed dosing regimen (Figure 6A) which correlated strongly with matched time point serum anti-RH5 IgG (Figure 6B).…”