Irradiated sporozoite vaccination induces sex-specific immune responses and protection against malaria in mice.
Irradiated sporozoite vaccination induces sex-specific immune responses and protection against malaria in mice.
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辐照子孢子疫苗接种可诱导小鼠性别特异性免疫反应并预防疟疾。
DOI:
10.1016/j.vaccine.2019.06.075
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发表时间:
2019
期刊:
影响因子:
5.5
通讯作者:
Klein,SabraL
中科院分区:
文献类型:
--
作者:
VomSteeg,LandonG;Flores-Garcia,Yevel;Zavala,Fidel;Klein,SabraL
In both preclinical animal studies and human clinical trials, adult females tend to develop greater adaptive immune responses than males following receipt of either viral or bacterial vaccines. While there is currently no approved malaria vaccine, several anti-sporozoite vaccines, including RTS,S/AS01 and attenuated sporozoite vaccines, are in development, but the impact of sex and age on their efficacy remains undefined. To examine sex differences in the efficacy of anti-sporozoite stage malaria vaccination, adult (10 weeks of age) or juvenile (11 days of age) male and female C3H mice were twice vaccinated with irradiated transgenicPlasmodium bergheisporozoites expressing theP. falciparumcircumsporozoite (CSP) protein and 45 days post boost vaccination, mice were challenged with transgenicP. bergheivia mosquito bite or intradermal challenge. Immunization with irradiated sporozoites resulted in greater protection against challenge in adult females, which was associated with greater anti-CSP antibody production and avidity, as well as greater hepatic, but not splenic, CD8+T cell IFNƴ production in adult females than adult males. No sex differences in adaptive immune responses or protection were observed in mice vaccinated prior to puberty, suggesting a role for sex steroid hormones. Depletion of testosterone in males increased, whereas rescue of testosterone decreased, anti-CSP antibody production, the number of antigen-specific CD8+T cells isolated from the liver, and protection following parasite challenge. Conversely, depletion of sex steroids in female mice did not alter vaccine-induced responses or protection following challenge. These data suggest that elevated testosterone concentrations in males reduce adaptive immunity and contribute to sex differences in malaria vaccine efficacy.
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DOI:
--
发表时间:
1976
期刊:
European Journal of Biochemistry
影响因子:
--
作者:
P. Rainey;E. Holler;M. Kula
通讯作者:
M. Kula
DOI:
--
发表时间:
2005
期刊:
European Journal of Biochemistry
影响因子:
--
作者:
D. Barker;J. Ebel;R. Jakes;C. Bruton
通讯作者:
C. Bruton
DOI:
10.1126/science.2435005
发表时间:
1987
期刊:
Science (New York, N.Y.)
影响因子:
--
作者:
Regan,L;Bowie,J;Schimmel,P
通讯作者:
Schimmel,P
影响因子:
56.9
作者:
DOOLITTLE, RF
通讯作者:
DOOLITTLE, RF
DOI:
--
发表时间:
1986
期刊:
The Journal of biological chemistry
影响因子:
--
作者:
Toth,MJ;Schimmel,P
通讯作者:
Schimmel,P