Akademik Veri Yönetim Sistemi
VACCINES, cilt.20, sa.10(10), ss.1-17, 2022 (SCI-Expanded)
Abstract: The causative agent of anthrax, Bacillus anthracis, evades the host immune response and
establishes infection through the production of binary exotoxins composed of Protective Antigen
(PA) and one of two subunits, lethal factor (LF) or edema factor (EF). The majority of vaccination
strategies have focused upon the antibody response to the PA subunit. We have used a panel
of humanised HLA class II transgenic mouse strains to define HLA-DR-restricted and HLA-DQrestricted CD4+ T cell responses to the immunodominant epitopes of PA. This was correlated with
the binding affinities of epitopes to HLA class II molecules, as well as the responses of two human
cohorts: individuals vaccinated with the Anthrax Vaccine Precipitated (AVP) vaccine (which contains
PA and trace amounts of LF), and patients recovering from cutaneous anthrax infections. The infected
and vaccinated cohorts expressing different HLA types were found to make CD4+ T cell responses
to multiple and diverse epitopes of PA. The effects of HLA polymorphism were explored using
transgenic mouse lines, which demonstrated differential susceptibility, indicating that HLA-DR1 and
HLA-DQ8 alleles conferred protective immunity relative to HLA-DR15, HLA-DR4 and HLA-DQ6.
The HLA transgenics enabled a reductionist approach, allowing us to better define CD4+ T cell
epitopes. Appreciating the effects of HLA polymorphism on the variability of responses to natural
infection and vaccination is vital in planning protective strategies against anthrax.
Keywords: anthrax; protective antigen; HLA class II; HLA transgenic; CD4 epitope; HLA-binding;
bacterial immunity