Comparing immunogenicity and protective efficacy of the yellow fever 17D vaccine in mice

Autor: Ji Ma, Robbert Boudewijns, Lorena Sanchez-Felipe, Niraj Mishra, Thomas Vercruysse, Dieudonné Buh Kum, Hendrik Jan Thibaut, Johan Neyts, Kai Dallmeier
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Emerging Microbes and Infections, Vol 10, Iss 1, Pp 2279-2290 (2021)
Druh dokumentu: article
ISSN: 22221751
2222-1751
DOI: 10.1080/22221751.2021.2008772
Popis: The live-attenuated yellow fever 17D (YF17D) vaccine is one of the most efficacious human vaccines and also employed as a vector for novel vaccines. However, in the lack of appropriate immunocompetent small animal models, mechanistic insight in YF17D-induced protective immunity remains limited. To better understand YF17D vaccination and to identify a suitable mouse model, we evaluated the immunogenicity and protective efficacy of YF17D in five complementary mouse models, i.e. wild-type (WT) BALB/c, C57BL/6, IFN-α/β receptor (IFNAR-/-) deficient mice, and in WT mice in which type I IFN signalling was temporally ablated by an IFNAR blocking (MAR-1) antibody. Alike in IFNAR-/- mice, YF17D induced in either WT mice strong humoral immune responses dominated by IgG2a/c isotype (Th1 type) antibodies, yet only when IFNAR was blocked. Vigorous cellular immunity characterized by CD4+ T-cells producing IFN-γ and TNF-α were mounted in MAR-1 treated C57BL/6 and in IFNAR-/- mice. Surprisingly, vaccine-induced protection was largely mouse model dependent. Full protection against lethal intracranial challenge and a massive reduction of virus loads was conferred already by a minimal dose of 2 PFU YF17D in BALB/c and IFNAR-/- mice, but not in C57BL/6 mice. Correlation analysis of infection outcome with pre-challenge immunological markers indicates that YFV-specific IgG might suffice for protection, even in the absence of detectable levels of neutralizing antibodies. Finally, we propose that, in addition to IFNAR-/- mice, C57BL/6 mice with temporally blocked IFN-α/β receptors represent a promising immunocompetent mouse model for the study of YF17D-induced immunity and evaluation of YF17D-derived vaccines.
Databáze: Directory of Open Access Journals
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