Stimulation of B Cell Immunity in Flavivirus-Naive Individuals by the Tetravalent Live Attenuated Dengue Vaccine TV003.
prospective_cohort · Level II
Where this comes from
- Record sourced from PubMed, PMID 33377126.
- Also identified by DOI 10.1016/j.xcrm.2020.100155 and PMC identifier 7762770.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The tetravalent live attenuated dengue vaccine candidate TV003 induces neutralizing antibodies against all four dengue virus serotypes (DENV1-DENV4) and protects against experimental challenge with DENV2 in humans. Here, we track vaccine viremia and B and T cell responses to this vaccination/challenge model to understand how vaccine viremia links adaptive immunity and development of protective antibody responses. TV003 viremia triggers an acute plasmablast response that, in combination with DENV-specific CD4<sup>+</sup> T cells, correlates with serum neutralizing antibodies. TV003 vaccinees develop DENV2-reactive memory B cells, including serotype-specific and multivalent specificities in line with the composition of serum antibodies. There is no post-challenge plasmablast response in vaccinees, although stronger and earlier post-TV003 plasmablast responses associate with sterile humoral protection from DENV2 challenge. TV003 vaccine triggers plasmablasts and memory B cells, which, with support from CD4<sup>+</sup> T cells, functionally link early vaccine viremia and the serum antibody responses.
Medical subject headings
- B-Lymphocytes
- Dengue Vaccines
- Flavivirus
- Vaccines, Attenuated