Tackling cutaneous herpes simplex virus disease with topical immunomodulators—a call to action
Journal
Clinical Microbiology Reviews
ISSN
0893-8512
Date Issued
2025-03-13
Author(s)
Javier Carbone-Schellman
Susan M. Bueno
Alexis M. Kalergis
Claudia A. Riedel
Pablo A. González
Type
journal-article
Abstract
Antivirals play important roles in restricting viral diseases. Nevertheless, they act on a relatively limited number of viruses and occasionally display partial effectiveness in some tissues or against escape variants. Although vaccination remains the most cost-effective approach for preventing microbial diseases, developing prophylactic or therapeutic solutions for pathogens, such as herpes simplex viruses (HSVs), that effectively reduce their clinical manifestations in the skin has proven exceptionally challenging despite extensive research. Alternatively, a less explored approach for tackling HSV skin infection involves using topical immunomodulatory molecules to potentiate the host’s innate antiviral immune responses. When applied directly to herpetic skin lesions where viral antigen is present, this strategy has the potential to elicit virus-specific adaptive immunity. Based on currently available data, we foresee substantial potential for this approach in addressing HSV skin infections, along with additional prospects to advance understanding of skin biology and apply relevant new findings to other dermatological conditions. However, due to the limited number of case studies evaluating this method and its safety profile, particularly in immunocompromised individuals and pregnant women, further research is crucial, especially to assess the effects of immunomodulators in these vulnerable populations. Here, we revisit and discuss the use of immunomodulatory molecules for potentiating the host immune response against HSV skin infection and call for action for increased research and clinical trials regarding the possible benefits of this latter strategy for treating HSV cutaneous disease and recurrences. We also revisit and discuss antivirals and vaccine candidates against HSVs.
Subjects
administration
;
topical
;
animals
;
antiviral agents
;
herpes simplex
;
humans
;
immunologic factors
;
immunomodulating agents
;
simplexvirus
;
aciclovir
;
amenamevir
;
beta interferon
;
brincidofovir
;
cidofovir
;
cutaneous t cell attracting chemokine
;
cxcl9 chemokine
;
epithelial derived neutrophil activating factor 78
;
gamma interferon
;
gamma interferon inducible protein 10
;
immunomodulating agent
;
interferon induced helicase c domain containing protein 1
;
interleukin 1
;
interleukin 12
;
interleukin 12p70
;
interleukin 15
;
interleukin 17
;
interleukin 1beta
;
interleukin 6
;
interleukin 8
;
macrophage inflammatory protein 1alpha
;
macrophage inflammatory protein 1beta
;
macrophage inflammatory protein 3alpha
;
monoclonal antibody
;
myeloid differentiation factor 88
;
nectin 1
;
penciclovir
;
protein vp22
;
rantes
;
retinoic acid inducible protein i
;
toll like receptor 2
;
toll like receptor 3
;
toll like receptor 4
;
tumor necrosis factor
;
virus antigen
;
antivirus agent
;
immunologic factor
;
immunomodulating agent
;
adaptive immunity
;
antiviral activity
;
cd8+ t lymphocyte
;
cell migration
;
cutaneous herpes simplex virus disease
;
dendritic cell
;
hek293t cell line
;
hela cell line
;
herpes simplex
;
human
;
immune response
;
immunotherapy
;
innate immunity
;
keratinocyte
;
nf kb signaling
;
nonhuman
;
phenotype
;
review
;
thp-1 cell line
;
vaccination
;
virus entry
;
virus load
;
virus replication
;
animal
;
drug effect
;
drug therapy
;
immunology
;
simplexvirus
;
topical drug administration
;
acyclovir
;
dendritic cells
;
herpetic skin lesions
;
herpetic skin recurrences
;
hsv
;
immune response modifiers
;
immunity
;
immunotherapy
;
therapy
;
vaccine