Toward the Eradication of Herpes Simplex Virus: Vaccination and Beyond

Herpes simplex virus (HSV) has coevolved with Homo sapiens for over 100,000 years, maintaining a tenacious presence by establishing lifelong, incurable infections in over half the human population. As of 2024, an effective prophylactic or therapeutic vaccine for HSV remains elusive. In this review, we independently screened PubMed, EMBASE, Medline, and Google Scholar for clinically relevant articles on HSV vaccines. We identified 12 vaccines from our literature review and found promising candidates across various classes, including subunit vaccines, live vaccines, DNA vaccines, and mRNA vaccines. Notably, several vaccines—SL-V20, HF10, VC2, and mRNA-1608—have shown promising preclinical results, suggesting that an effective HSV vaccine may be within reach. Additionally, several other vaccines such as GEN-003 (a subunit vaccine from Genocea), HerpV (a subunit vaccine from Agenus), 0ΔNLS/RVx201 (a live-attenuated replication-competent vaccine from Rational Vaccines), HSV 529 (a replication-defective vaccine from Sanofi Pasteur), and COR-1 (a DNA-based vaccine from Anteris Technologies) have demonstrated potential in clinical trials. However, GEN-003 and HerpV have not advanced further despite promising results. Continued progress with these candidates brings us closer to a significant breakthrough in preventing and treating HSV infections.