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Afshana Quadiri1, Yassir Lekbach1, Elhoucine Elfatimi1

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Developing new herpes simplex virus (HSV) vaccines is challenging. Novel Prime/Pull/Keep (PPK) vaccine strategies show promise in preclinical trials for inducing durable T cell immunity against HSV-1 and HSV-2.

Keywords:
PPK vaccinesasymptomaticclinical trialsepitopesherpes simplex virus (HSV-1 and HSV-2)immunotherapeuticsymptomaticvaccines

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Area of Science:

  • Immunology
  • Vaccinology
  • Virology

Background:

  • Despite advances in medical science, effective vaccines against herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) remain elusive.
  • Previous therapeutic vaccine candidates, mainly targeting neutralizing antibodies, have failed to provide lasting protection against recurrent herpes.
  • Recent breakthroughs in omics, AI, and deep learning offer new avenues for designing targeted herpes vaccine strategies.

Purpose of the Study:

  • To explore novel tissue-targeted vaccine strategies for inducing potent and durable HSV-specific CD4+ and CD8+ T cell immunity.
  • To investigate the potential of Prime/Pull/Keep (PPK) vaccine candidates in preclinical models of recurrent ocular and genital herpes.
  • To discuss the development of a clinically adaptable, all-in-one PPK mucosal therapeutic vaccine for single administration.

Main Methods:

  • Utilizing "asymptomatic" epitopes/antigens to prime CD4+ and CD8+ T cells (Prime).
  • Employing T cell-attracting chemokines like CXCL11 to recruit primed T cells to infected tissues (Pull).
  • Using survival cytokines (IL-2, IL-7, IL-15) or mucosal chemokines (CXCL17, CCL28) to maintain tissue-resident T cells (Keep).

Main Results:

  • PPK vaccine candidates have demonstrated success in preclinical animal models for recurrent ocular and genital herpes.
  • The PPK strategy aims to induce robust and durable T cell immunity at both sensory ganglia and mucocutaneous tissues.
  • This approach targets central and peripheral immunity for comprehensive protection against HSV.

Conclusions:

  • Recent advancements facilitate the rational design of tissue-targeted herpes vaccine strategies.
  • PPK vaccines represent a promising approach for achieving potent and durable HSV-specific T cell immunity.
  • The development of a single-administration PPK mucosal therapeutic vaccine is a key future direction.