. Author manuscript; available in PMC: 2022 Nov 1.

Published in final edited form as: Adv Drug Deliv Rev. 2021 Sep 1;178:113956. doi: 10.1016/j.addr.2021.113956

Table 3:

Summary of studies of vaginal HSV vaccination in animals

Vaccine type	Animal model	Delivery modality	Prime/boost (routes)	Adjuvant	Systemic Response	Mucosal Response	Remarks on efficacy	Source
Protein: HSV-2 gp	Mice	Nanoparticle suspension	Vaginal	Calcium phosphate (CAP) NPs	Enhanced IgG with CAP	Modest IgG and high IgA	CAP induced long-lived neutralizing Abs in serum and mucosa that protected against live HSV-2 infection	[109]
Protein: HSV recombinant gB (rgB)	Mice	Solution	Vaginal	CpG oligodeoxynucleotides (ODN)	Serum IgG and IgA	High vaginal IgG and IgA; high IgG at distal mucosal sites with CpG ODN	CpG ODN significantly enhanced mucosal response and survival against HSV challenge	[134]
Protein: HSV-2 gp	Mice	Solution	Vaginal/vaginal	CpG ODN	Strong T_H1-like response in DLNs and spleen; splenic IgG	Rapid CC chemokine (MIP-1α, MIP-1β, RANTES) and CXC chemokine (MIP-2 and IP-10) response; high IgG	CpG ODN skewed a T_H1 response that conferred protection against vaginal HSV challenge	[135]
Protein: Lipopeptide - HSV-2 gB498–505 - PAN DR (CD4⁺ and CD8⁺ T cell epitopes)	Mice	Solution	Vaginal/vaginal	Conjugated palmitic acid	Splenic gB-specific CTLs; high IFN-γ, IL-2 (T_H1) and IL-12-producting CD8⁺ T cells in ILN	Induction of IFN-γ-producing CD8⁺ T cells; memory CD8⁺ T cell pop. 60 days after vacc.	Dual-epitope lipopeptide induced CD8⁺ T cell-mediated protection against HSV	[107]
Protein + viral vector: lipopeptide and adenovirus (rAdv5) - HSV-2 gB489–505 (CD8⁺ T cell epitope)	Mice	Solution	Vaginal (lipo)/vaginal (rAdv5)	n/a	Not reported	Induction of IFN-γ-producing CD8⁺ T cells; CTL responses 8 months after vacc. with lipo/rAdv5	Heterologous prime/boost induced potent and durable CD8⁺ T cell response that protected against HSV	[152]
Viral vector: HPV pseudovirus (PsV) - HSV-2 gB or gD	Mice	Solution	Vaginal (+ i.m.)	n/a	Splenic memory CD8⁺ T cells; serum HSV-neutralizing Abs	IFN-γ and TNF-α-secreting CD8⁺ T cells; CD8⁺ T_RM cells 4 wks after vacc.	Ivag and ivag + i.m. vacc. with combined gB and gD improved survival and reduced genital lesions and viral shedding	[108]