Restrained expansion of the recall germinal center response as biomarker of protection for influenza vaccination in mice

Autoři: Laurens P. Kil aff001;  Joost Vaneman aff001;  Joan E. M. van der Lubbe aff001;  Dominika Czapska-Casey aff001;  Jeroen T. B. M. Tolboom aff001;  Ramon Roozendaal aff001;  Roland C. Zahn aff001;  Harmjan Kuipers aff001;  Laura Solforosi aff001
Působiště autorů: Janssen Vaccines & Prevention B.V., Pharmaceutical Companies of Johnson and Johnson, Leiden, The Netherlands aff001
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0225063


Correlates of protection (CoP) are invaluable for iterative vaccine design studies, especially in pursuit of complex vaccines such as a universal influenza vaccine (UFV) where a single antigen is optimized to elicit broad protection against many viral antigenic variants. Since broadly protective antibodies against influenza virus often exhibit mutational evidence of prolonged diversification, we studied germinal center (GC) kinetics in hemagglutinin (HA) immunized mice. Here we report that as early as 4 days after secondary immunization, the expansion of HA-specific GC B cells inversely correlated to protection against influenza virus challenge, induced by the antigen. In contrast, follicular T helper (TFH) cells did not expand differently after boost vaccination, suggestive of a B-cell intrinsic difference in activation and differentiation inferred by protective antigen properties. Importantly, differences in antigen dose only affected GC B-cell frequencies after primary immunization. The absence of accompanying differences in total anti-HA or epitope-specific antibody levels induced by vaccines of different efficacy suggests that the GC B-cell response upon revaccination represents an early and unique marker of protection that may significantly accelerate the pre-clinical phase of vaccine development.

Klíčová slova:

Antibodies – Antibody response – B cells – Enzyme-linked immunoassays – Immune response – Vaccination and immunization – Vaccines – Antigen isotypes


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Článek vyšel v časopise


2019 Číslo 11