Terminal deoxynucleotidyl Transferase is not required for antibody response to polysaccharide vaccines against Streptococcus pneumoniae and Salmonella Typhi

Academic Article

Abstract

  • B cell antigen receptor (BCR) diversity increases by several orders of magnitude due to the 26 action of Terminal deoxynucleotidyl Transferase (TdT) during V(D)J recombination. Unlike 27 adults, infants have limited BCR diversity, in part due to reduced expression of TdT. Since 28 human infants and young mice respond poorly to polysaccharide vaccines such as pneumococcal 29 polysaccharide vaccine, Pneumovax®23, and Vi polysaccharide (ViPS) of Salmonella enterica 30 serovar Typhi (S. Typhi), we tested the contribution of TdT-mediated BCR diversity in response 31 to these vaccines. We found that TdT+/- and TdT-/- mice generate comparable antibody responses 32 to Pneumovax®23 and survive Streptococcus pneumoniae challenge. Moreover, passive 33 immunization of B cell-deficient mice with serum from Pneumovax®23-immunized TdT+/- or 34 TdT-/- mice conferred protection. TdT+/- and TdT-/- mice generated comparable levels of anti- 35 ViPS antibodies and antibody-dependent, complement-mediated bactericidal activity against S. 36 Typhi in vitro. To test the protective immunity conferred by ViPS immunization in vivo, TdT+/- 37 and TdT-/- mice were challenged with a chimeric Salmonella enterica serovar Typhimurium (S. 38 Typhimurium) strain expressing ViPS, since mice are non-permissive hosts for S. Typhi 39 infection. Compared to their unimmunized counterparts, immunized TdT+/- and TdT-/- mice 40 challenged with ViPS-expressing S. Typhimurium exhibited a significant reduction in bacterial 41 burden and liver pathology. These data suggest that impaired antibody response to 42 Pneumovax®23 and ViPS vaccine in the young is not due to limited TdT-mediated BCR 43 diversification.
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    Keywords

  • TdT; Salmonella; Pneumococcus; antibodies; polysaccharide vaccine
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    Author List

  • Belde V; Cravens M; Gulandijany D; Walker JA; Palomo-Caturla I; Alugupalli AS; Sandilya V; Mahmoud T; Baumler AJ; Kearney JF
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  • In Press
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  • 200