Rational Design of T Lymphocyte Epitope-Based Vaccines Against Coccidioides Infection

Abstract

Coccidioidomycosis is a potentially life-threatening mycosis endemic to the Southwestern USA and some arid regions of Central and South America. A vaccine against Coccidioides infection would benefit over 30-million people who reside in or visit the endemic regions. Vaccine candidates against systemic fungal infections come in many forms. Live attenuated vaccines are derived from disease-causing pathogens and generally stimulate excellent protective immunity. Since attenuated vaccines contain living microbes, there is a degree of unpredictability raising concerns regarding safety and stability. Generation of a subunit vaccine has initiated efforts to design a safe reagent suitable for administration to humans at risk of coccidioidomycosis. Epitope-based vaccines allow for eliciting specific protective immune responses and removal of potentially detrimental sequences to improve safety. This chapter describes methods for the identification of T cell epitopes derived from Coccidioides antigens, design, and production of a recombinant vaccine containing multiple T cell epitopes, and evaluation of its protective efficacy and vaccine immunity against pulmonary Coccidioides infection using a strain of transgenic mice that express a human MHC II molecule.

Glucan-Chitin Particles Enhance Th17 Response and Improve Protective Efficacy of a Multivalent Antigen (rCpa1) against Pulmonary Coccidioides posadasii Infection

“…The C terminus of each antigenic peptide was flanked by a GPGPG spacer to avoid the processing of junctional epitopes, as shown in Fig. 1A (6,24). The nucleotide sequence designed to encode rCpa1 was codon optimized for translation by Escherichia coli.…”

“…Additionally, potential antigenic epitopes can be identified in silico, since the genome sequences of both Coccidioides posadasii and Coccidioides immitis are available (33). The newly created antigen rCpa1 contains the most immunogenic fragment of Ag2/Pra, Cs-Ag, Pmp1, and five peptides derived from Pep1, Amn1, and Plb that contain human epitopes (11,18,24). These antigens were selected because they are expressed at maximum levels during different stages of the parasitic cycle.…”

“…A single bacterially expressed recombinant Coccidioides polypeptide (rCpa1) was designed to contain the most immunogenic fragment of Ag2/Pra (aa 1 to 106; NCBI Reference Sequence Database accession no. XM_003069107), the full lengths of Cs-Ag (XM_003056932) and Pmp1 (XM_003069228), and the five most promiscuous immunodominant T-cell epitopes derived from Pep1, Amn1, and Plb (6,11,24). The N terminus of each antigen and epitope was flanked by a GPGPG spacer to avoid the processing of junctional epitopes (6).…”

Effect of Qing Chang oral liquid on the treatment of artificially infected chicken coccidiosis and the cellular immunity

“…Mature T cells are divided into CD4 + T cells and CD8 + T cells according to the characteristic molecules on the cell surface. It has been found that CD4 + T lymphocytes, after being stimulated by antigen, promote the activity of natural killer cells and enhance the cytotoxic effect of T cells and play an important role in fighting coccidiosis primary infection (Hurtgen & Hung, 2017 ). CD8 + T lymphocytes play vital roles in virus immediate‐early antigens mediate protective immunity (Reddehase et al., 1987 ).…”

Emerging Concepts and Technologies in Vaccine Development

“…A computationally designed antigen found to be protective in animal models was first reported for the respiratory syncytial virus (RSV) F antigen in 2013 ( 79 ). Many challenging vaccine targets have since been developed rationally for HIV ( 80 – 82 ), hepatitis C ( 83 , 84 ), herpes ( 85 ), Zika ( 86 , 87 ), RSV ( 82 ), HPV ( 88 ), as well as for bacteria ( 82 , 89 ), fungi ( 90 ), and cancers ( 91 ). Rational vaccine design has also been utilized to improve VLP and NP vaccines by selecting a repetitive and predictive protein backbone structure for enhanced antigen presentation ( 92 ).…”