Towards a Rational Design of an Asymptomatic Clinical Herpes Vaccine: The Old, the New, and the Unknown

Table 2

Herpes vaccine formulas used in clinical trials.

Type of HSV vaccine	Formulation	Strain	Route of administration	Clinical outcome
Live	Live HSV	Varies	Autoinoculation	(i) Unsuccessful; (ii) Recurrence not affected; (iii) Lesions at infection and injection sites [125, 126]
Live-attenuated	Recombinant R7020	HSV-1(F) and HSV-2(G)	Intramuscular	(i) Unsuccessful; (ii) Poor immunogenicity; (iii) Adverse effects in HSV-1; seropositive individuals [127, 128]
Whole inactivated	Heat inactivated (Lupidon G and H)	HSV-2(Silow); and HSV-1(L3)	Subcutaneous	(i) Statistically significant effect on recurrence of genital and facial herpes [129–131]
	Formalin inactivated	—	—	(ii) No significant difference in recurrence compared to placebo [132]
Inactivated subunit	Skinner: Ac NFU1, (S-) MRC	HSV-1; (Troisbell)	Subcutaneous	(i) Some statistically significant results in vaccinated males; (ii) No consistent efficacy or immunogenicity [133]
Recombinant subunit (glycoproteins)	Chiron gD2gB2-MF59	HSV-2	Intramuscular	(i) No significant effects on recurrence or shedding of virus [17]
	GlaxoSmithKline gD2-Alum MPL	HSV-2	Intramuscular	(ii) Fewer recurrences; (iii) Higher antibody and gD2-specific EIA titers compared to placebo [1, 134]
Disabled infectious single cycle (DISC)	TA-HSV-2	HSV-2(25766); HSV-1(HFEM); HSV-1(SC16); HSV-1(KOS); HSV-1(tsQ26)	?	(i) Good immunogenicity in early clinical trials; (ii) Unsuccessful phase II trials; (iii) No significant differences in recurrences or asymptomatic shedding compared to placebo [135]

The table summaries past and present HSV vaccine formulations, HSV-1/2 strains used, route of administration, and clinical outcomes.