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<p><i>Candida</i> species, including <i>Candida albicans</i> and <i>Candida auris</i>, represent a growing public health concern due to their increasing prevalence and resistance to antifungal agents. <i>C. albicans</i> is known for causing both superficial and invasive infections, while <i>C. auris</i> is a newly emerged, multidrug-resistant pathogen responsible for severe hospital outbreaks with a high mortality rate of ~ 60% in bloodstream infections. Vaccine candidates targeting <i>C. albicans</i> hyphal cell wall proteins Als3p and Hyr1p have shown protective efficacy in mice. NDV-3A, an alum-formulated Als3p-based vaccine, protected against recurrent vulvovaginal candidiasis in women. We earlier showed that both Als3p and Hyr1p have orthologs in <i>C. auris</i>, and that the NDV-3A vaccine, alongside an anti-Hyr1p monoclonal antibody, protected mice from multidrug resistant <i>C. auris</i> candidemia. Here, we optimized VXV-01, an Als3p and Hyr1p dual antigen vaccine formulated with the clinical-stage adjuvant CAF01, demonstrating robust immunity and CD4 T cell-dependent protection against lethal <i>C. albicans</i> and <i>C. auris</i>. The VXV-01 vaccine did not antagonize antifungal drug therapy and showed higher overall mouse survival than mice receiving the vaccine or antifungal drug alone, albeit this difference did not reach statistical significance. This study highlights the potential of VXV-01 in providing durable protective immunity against hematogenously disseminated <i>C. albicans</i> and <i>C. auris</i> and mucosal <i>C. albicans</i> infections.</p>

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Next-generation Candida albicans vaccine VXV-01 containing recombinant Als3p and Hyr1p antigens for invasive Candida infections

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月15日

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  • Shakti Singh,
  • Eman G. Youssef,
  • Ashley Barbarino,
  • Haley Hautau,
  • Sunna Nabeela,
  • Teclegiorgis Gebremariam,
  • Sondus Alkhazraji,
  • Gary Ostroff,
  • Dennis Christensen,
  • Terrence Cochrane,
  • Ashraf S. Ibrahim

摘要

Candida species, including Candida albicans and Candida auris, represent a growing public health concern due to their increasing prevalence and resistance to antifungal agents. C. albicans is known for causing both superficial and invasive infections, while C. auris is a newly emerged, multidrug-resistant pathogen responsible for severe hospital outbreaks with a high mortality rate of ~ 60% in bloodstream infections. Vaccine candidates targeting C. albicans hyphal cell wall proteins Als3p and Hyr1p have shown protective efficacy in mice. NDV-3A, an alum-formulated Als3p-based vaccine, protected against recurrent vulvovaginal candidiasis in women. We earlier showed that both Als3p and Hyr1p have orthologs in C. auris, and that the NDV-3A vaccine, alongside an anti-Hyr1p monoclonal antibody, protected mice from multidrug resistant C. auris candidemia. Here, we optimized VXV-01, an Als3p and Hyr1p dual antigen vaccine formulated with the clinical-stage adjuvant CAF01, demonstrating robust immunity and CD4 T cell-dependent protection against lethal C. albicans and C. auris. The VXV-01 vaccine did not antagonize antifungal drug therapy and showed higher overall mouse survival than mice receiving the vaccine or antifungal drug alone, albeit this difference did not reach statistical significance. This study highlights the potential of VXV-01 in providing durable protective immunity against hematogenously disseminated C. albicans and C. auris and mucosal C. albicans infections.