TY - JOUR
T1 - Incomplete genetic reconstitution of B cell pools contributes to prolonged immunosuppression after measles
AU - Petrova, Velislava N.
AU - Sawatsky, Bevan
AU - Han, Alvin X.
AU - Laksono, Brigitta M.
AU - Walz, Lisa
AU - Parker, Edyth
AU - Pieper, Kathrin
AU - Anderson, Carl A.
AU - de Vries, Rory D.
AU - Lanzavecchia, Antonio
AU - Kellam, Paul
AU - von Messling, Veronika
AU - de Swart, Rik L.
AU - Russell, Colin A.
PY - 2019
Y1 - 2019
N2 - Measles is a disease caused by the highly infectious measles virus (MeV) that results in both viremia and lymphopenia. Lymphocyte counts recover shortly after the disappearance of measles-associated rash, but immunosuppression can persist for months to years after infection, resulting in increased incidence of secondary infections. Animal models and in vitro studies have proposed various immunological factors underlying this prolonged immune impairment, but the precise mechanisms operating in humans are unknown. Using B cell receptor (BCR) sequencing of human peripheral blood lymphocytes before and after MeV infection, we identified two immunological consequences from measles underlying immunosuppression: (i) incomplete reconstitution of the naïve B cell pool leading to immunological immaturity and (ii) compromised immune memory to previously encountered pathogens due to depletion of previously expanded B memory clones. Using a surrogate model of measles in ferrets, we investigated the clinical consequences of morbillivirus infection and demonstrated a depletion of vaccine-acquired immunity to influenza virus, leading to a compromised immune recall response and increased disease severity after secondary influenza virus challenge. Our results show that MeV infection causes changes in naïve and memory B lymphocyte diversity that persist after the resolution of clinical disease and thus contribute to compromised immunity to previous infections or vaccinations. This work highlights the importance of MeV vaccination not only for the control of measles but also for the maintenance of herd immunity to other pathogens, which can be compromised after MeV infection.
AB - Measles is a disease caused by the highly infectious measles virus (MeV) that results in both viremia and lymphopenia. Lymphocyte counts recover shortly after the disappearance of measles-associated rash, but immunosuppression can persist for months to years after infection, resulting in increased incidence of secondary infections. Animal models and in vitro studies have proposed various immunological factors underlying this prolonged immune impairment, but the precise mechanisms operating in humans are unknown. Using B cell receptor (BCR) sequencing of human peripheral blood lymphocytes before and after MeV infection, we identified two immunological consequences from measles underlying immunosuppression: (i) incomplete reconstitution of the naïve B cell pool leading to immunological immaturity and (ii) compromised immune memory to previously encountered pathogens due to depletion of previously expanded B memory clones. Using a surrogate model of measles in ferrets, we investigated the clinical consequences of morbillivirus infection and demonstrated a depletion of vaccine-acquired immunity to influenza virus, leading to a compromised immune recall response and increased disease severity after secondary influenza virus challenge. Our results show that MeV infection causes changes in naïve and memory B lymphocyte diversity that persist after the resolution of clinical disease and thus contribute to compromised immunity to previous infections or vaccinations. This work highlights the importance of MeV vaccination not only for the control of measles but also for the maintenance of herd immunity to other pathogens, which can be compromised after MeV infection.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85074347685&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31672862
U2 - https://doi.org/10.1126/sciimmunol.aay6125
DO - https://doi.org/10.1126/sciimmunol.aay6125
M3 - Article
C2 - 31672862
SN - 2470-9468
VL - 4
JO - Science immunology
JF - Science immunology
IS - 41
ER -