Campuzano Althea, Pentakota Komali Devi, Liao Yu-Rou, Zhang Hao, Wiederhold Nathan P, Ostroff Gary R, Hung Chiung-Yu
Department of Molecular Microbiology and Immunology, The University of Texas at San Antonio, San Antonio, TX 78249, USA.
Department of Pathology, Graduate School of Biomedical Sciences, UT Health, San Antonio, TX 78229, USA.
Vaccines (Basel). 2024 Jan 9;12(1):67. doi: 10.3390/vaccines12010067.
Coccidioidomycosis is caused by () and (), which have a 4-5% difference in their genomic sequences. There is an urgent need to develop a human vaccine against both species. A previously created recombinant antigen (rCpa1) that contains multiple peptides derived from isolate C735 is protective against the autologous isolate. The focus of this study is to evaluate cross-protective efficacy and immune correlates by the rCpa1-based vaccine against both species of . DNA sequence analyses of the homologous genes for the rCpa1 antigen were conducted for 39 and 17 clinical isolates of and , respectively. Protective efficacy and vaccine-induced immunity were evaluated for both C57BL/6 and human HLA-DR4 transgenic mice against five highly virulent isolates of and . There are total of seven amino acid substitutions in the rCpa1 antigen between and . Both C57BL/6 and HLA-DR4 mice that were vaccinated with an rCpa1 vaccine had a significant reduction of fungal burden and increased numbers of IFN-γ- and IL-17-producing CD4+ T cells in the first 2 weeks post challenge. These data suggest that rCpa1 has cross-protection activity against and pulmonary infection through activation of early Th1 and Th17 responses.
球孢子菌病由()和()引起,它们的基因组序列有4 - 5%的差异。迫切需要开发一种针对这两种菌的人类疫苗。一种先前构建的包含来自分离株C735的多种肽段的重组抗原(rCpa1)对自体分离株具有保护作用。本研究的重点是评估基于rCpa1的疫苗对这两种菌的交叉保护效力和免疫相关性。分别对39株和17株()和()的临床分离株进行了rCpa1抗原同源基因的DNA序列分析。评估了C57BL/6和人HLA - DR4转基因小鼠针对5株高毒力()和()分离株的保护效力和疫苗诱导的免疫力。()和()之间的rCpa1抗原共有7个氨基酸替换。接种rCpa1疫苗的C57BL/6和HLA - DR4小鼠在攻毒后的前2周真菌负荷显著降低,产生IFN -γ和IL - 17的CD4 + T细胞数量增加。这些数据表明,rCpa1通过激活早期Th1和Th17反应对()和()肺部感染具有交叉保护活性。