In:
The Journal of Immunology, The American Association of Immunologists, Vol. 196, No. 1_Supplement ( 2016-05-01), p. 146.12-146.12
Kurzfassung:
Anthrax Vaccine Adsorbed (AVA) vaccination protects against anthrax infection by eliciting a neutralizing antibody response. However, protective antibody titers are not observed in human sera until at least three vaccinations have been administered over six months. Even then, humoral responses to AVA do not provide long-term immunity without an annual booster, presenting a serious challenge in public health. We followed six healthy volunteers over the standard five-dose, 18-month AVA schedule to characterize immunoglobulin genetics during vaccination. Plasmablasts were isolated one week after each vaccination and natively-paired heavy- and light-chain immunoglobulin mRNA were sequenced. Immunoglobulin sequences were analyzed for mutations and clonal evolution. After primary vaccination, the average mutation frequency of observed plasmablast lineages indicated they were derived from previously affinity matured B cells (6.1–7.7%). Many sequences had very high mutation frequencies ( & gt;10%), a characteristic that has been linked to multiple antigen exposures. We synthesized antibodies from these lineages and tested them against a panel of human antigens. While they had little to no affinity to anthrax antigens, they displayed significant affinity to a variety of autoantigens. These memory lineages were non-persistent, and we observed naïve B cell activation after secondary vaccination. We tested antibodies from naïve-derived lineages first observed after secondary vaccination and found these to be anthrax-specific and non-autoreactive. Thus, while primary AVA vaccination elicits a robust memory response, it is non-protective and delays anthrax-specific naïve B cell recruitment until secondary vaccination.
Materialart:
Online-Ressource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.196.Supp.146.12
Sprache:
Englisch
Verlag:
The American Association of Immunologists
Publikationsdatum:
2016
ZDB Id:
1475085-5
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