The Path Towards Effective Long-Lasting Tissue-Targeted Prime/Pull/Keep Herpes Simplex Therapeutic Vaccines

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.