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2015 ; 89
(5
): 2842-8
Nephropedia Template TP
gab.com Text
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Twit Text #
English Wikipedia
Lymph node but not intradermal injection site macrophages are critical for
germinal center formation and antibody responses to rabies vaccination
#MMPMID25540370
Lytle AG
; Shen S
; McGettigan JP
J Virol
2015[Mar]; 89
(5
): 2842-8
PMID25540370
show ga
Replication-deficient rabies virus (RABV)-based vaccines induce rapid and potent
antibody responses via T cell-independent and T cell-dependent mechanisms. To
further investigate early events in vaccine-induced antibody responses against
RABV infections, we studied the role of macrophages as mediators of RABV-based
vaccine immunogenicity. In this report, we show that a recombinant matrix
gene-deleted RABV-based vaccine (rRABV-?M) infects and activates primary murine
macrophages in vitro. Immunization of mice with live RABV-based vaccines results
in accumulation of macrophages at the site of immunization, which suggests that
macrophages in tissues support the development of effective anti-RABV B cell
responses. However, we show that draining lymph node macrophages, but not
macrophages at the site of immunization, are essential for the generation of
germinal center B cells, follicular T helper cells, and RABV-specific antibodies.
Our findings have implications for the design of new RABV-based vaccines for
which early immunological events are important for the protection against RABV in
postexposure settings. IMPORTANCE: More than two-thirds of the world's population
live in regions where rabies is endemic. Postexposure prophylaxis is the primary
means of treating humans. Identifying immunological principles that guide the
development of rapid and potent antibody responses against rabies infections will
greatly increase our ability to produce more-effective rabies vaccines. Here we
report that macrophages in the draining lymph node, but not in the tissue at the
site of immunization are important for vaccine-induced antibody responses to
rabies. Information gleaned from this study may help guide the development of a
single-dose vaccine against rabies infections.