BibTex format
@article{Habibi:2015:10.1164/rccm.201412-2256OC,
author = {Habibi, MS and Jozwik, A and Makris, S and Dunning, J and Paras, A and DeVincenzo, JP and de, Haan CA and Wrammert, J and Openshaw, PJ and Chiu, C and The, MOSAIC Investigators},
doi = {10.1164/rccm.201412-2256OC},
journal = {American Journal of Respiratory and Critical Care Medicine},
title = {Impaired antibody-mediated protection and defective IgA B cell memory in experimental infection of adults with respiratory syncytial virus},
url = {http://dx.doi.org/10.1164/rccm.201412-2256OC},
volume = {191},
year = {2015}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Rationale: Despite relative antigenic stability, respiratory syncytial virus (RSV) re-infects throughout life. After >40 years of research, no effective human vaccine exists and correlates of protection remain poorly defined. Most current vaccine candidates seek to induce high levels of RSV-specific serum neutralizing antibodies, which are associated with reduced RSV-related hospitalization rates in observational studies but may not actually prevent infection. Objectives: Characterize correlates of protection from infection and the generation of RSV-specific humoral memory to promote effective vaccine development. Methods: We inoculated 61 healthy adults with live RSV and studied protection from infection by serum and mucosal antibody. We analyzed RSV-specific peripheral blood plasmablast and memory B cell frequencies and antibody longevity. Measurements and Main Results: Despite moderately high levels of pre-existing serum antibody, 34 (56%) became infected, of whom 23 (68%) developed symptomatic colds. Prior RSV-specific nasal IgA correlated significantly more strongly with protection from PCR-confirmed infection than serum neutralizing antibody. Increases in virus-specific antibody titers were variable and transient in infected subjects, but correlated with plasmablasts that peaked around day 10. During convalescence, only IgG (and no IgA) RSV-specific memory B cells were detectable in peripheral blood. This contrasted with natural influenza infection, where virus-specific IgA memory B cells were readily recovered. Conclusions: This observed specific defect in IgA memory may partly explain RSV's ability to cause recurrent symptomatic infections. If so, vaccines able to induce durable RSV-specific IgA responses may be more protective than those generating systemic antibody alone.
AU - Habibi,MS
AU - Jozwik,A
AU - Makris,S
AU - Dunning,J
AU - Paras,A
AU - DeVincenzo,JP
AU - de,Haan CA
AU - Wrammert,J
AU - Openshaw,PJ
AU - Chiu,C
AU - The,MOSAIC Investigators
DO - 10.1164/rccm.201412-2256OC
PY - 2015///
SN - 1535-4970
TI - Impaired antibody-mediated protection and defective IgA B cell memory in experimental infection of adults with respiratory syncytial virus
T2 - American Journal of Respiratory and Critical Care Medicine
UR - http://dx.doi.org/10.1164/rccm.201412-2256OC
UR - http://www.ncbi.nlm.nih.gov/pubmed/25730467
UR - https://www.atsjournals.org/doi/10.1164/rccm.201412-2256OC
UR - http://hdl.handle.net/10044/1/21615
VL - 191
ER -
