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Inability To Evoke a Long-Lasting Protective Immune Response to Respiratory Syncytial Virus Infection in Mice Correlates with Ineffective Nasal Antibody Responses

Richard Singleton, Nathalie Etchart, Sam Hou, and Lisa Hyland^*

Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire RG20 7NN, United Kingdom

Received 24 March 2003/ Accepted 1 August 2003

Long-lasting protective antibody is not normally generated in children following primary respiratory syncytial virus (RSV) infection, frequently leading to reinfection. We used the BALB/c mouse model to examine the role of the nasal-associated lymphoid tissue and the bone marrow in the generation of RSV-specific long-lasting plasma cells, with a view to further understanding the mechanisms responsible for the poorly sustained RSV antibody levels following primary infection. We show here that substantial numbers of RSV-specific plasma cells were generated in the bone marrow following challenge, which were maintained thereafter. In contrast, in the nasal-associated lymphoid tissue, RSV-specific plasma cell numbers waned quickly both after primary infection and after challenge and were not maintained at a higher level after boosting. These data indicate that the inability to generate a robust local mucosal response in the nasal tissues may contribute substantially to the likelihood of subsequent reinfection and that the presence of serum anti-RSV antibody without local protection is not enough to protect against reinfection.

Present address: INSERM U404 "Immunité et Vaccination," IFR 74-CERVI, 69365 Lyon Cedex 07, France.

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