Search Results (104)

Herpes simplex viruses (HSV-1 and HSV-2) are highly prevalent human pathogens that establish lifelong latency in sensory neurons, posing a persistent challenge to global public health. Their clinical manifestations range from mild, self-limiting orolabial lesions to severe, life-threatening conditions such as disseminated neonatal infections, focal encephalitis, and herpetic stromal keratitis, which can lead to irreversible corneal blindness. Beyond direct pathology, HSV-mediated genital ulcerative disease (GUD) significantly enhances mucosal susceptibility to HIV-1 and other sexually transmitted infections, amplifying co-infection risk and disease burden. Despite decades of clinical reliance on nucleoside analogues such as acyclovir, the therapeutic landscape has stagnated with rising antiviral resistance, toxicity associated with prolonged use, and the complete inability of current drugs to eliminate latency or prevent reactivation continue to undermine effective disease control. These persistent gaps underscore an urgent need for next-generation antivirals that operate through fundamentally new mechanisms. Marine ecosystems, the planet’s most chemically diverse environments, are providing an expanding repertoire of antiviral compounds with significant therapeutic promise. Recent discoveries reveal that marine-derived polysaccharides, sulfated glycans, peptides, alkaloids, and microbial metabolites exhibit remarkably potent and multi-targeted anti-HSV activities, disrupting viral attachment, fusion, replication, and egress, while also reshaping host antiviral immunity. Together, these agents showcase mechanisms and scaffolds entirely distinct from existing therapeutics. This review integrates emerging evidence on structural diversity, mechanistic breadth, and translational promise of marine natural products with anti-HSV activity. Collectively, these advances position marine-derived compounds as powerful, untapped scaffolds capable of reshaping the future of HSV therapeutics. Full article

HSV-2 is the main pathogen causing genital herpes, and its infection increases the infection and transmission of HIV-1. Currently, there are no vaccines to prevent HSV-2 infection or treatment that can fully cure it. Mining key host factors that regulate HSV-2 replication and elucidating their specific regulatory mechanisms are crucial for understanding virus–host interactions and discovering new antiviral targets. In the current study, we identified DDX43 as a cellular factor involved in the suppression of HSV-2 replication through comparative transcriptomic analyses of HSV-2-infected epithelial cells, followed by experimental validation. Comprehensive transcriptomic profiling revealed distinct host cellular gene expression patterns in HeLa and ARPE-19 cell lines post HSV-2 infection. Subsequent orthogonal partial least-squares discriminant analysis (OPLS-DA) pinpointed DDX43 as one of the principal mediators distinguishing the host response between HSV-2-infected HeLa and ARPE-19 cells. Furthermore, overexpression of DDX43 inhibited HSV-2 replication, whereas knockdown of endogenous DDX43 enhanced HSV-2 replication. Additional experiments revealed that human DDX43 inhibits HSV-2 replication in an interferon-independent manner. This study demonstrates that DDX43 serves as a host regulator against HSV-2 infection, underscoring the power of comparative transcriptomics in identifying novel host proteins that modulate viral replications. Full article

Background: Herpes simplex virus (HSV) is a neurotropic virus that can be categorized into two serotypes: HSV-1 and HSV-2. HSV-1 causes symptoms such as herpes labialis, herpetic keratitis, genital ulcers, and encephalitis, and primarily establishes latent infection in the trigeminal ganglion. The complexity of membrane fusion mechanisms and potential infection in nerves allow HSV to easily evade recognition and clearance by host immune cells. Therefore, developing a vaccine that can prevent both primary and reactivated HSV-1 infection is critical. Currently, no preventive or therapeutic HSV-1 vaccines have been approved for marketing. Methods: In this study, we utilized the gC, gD, and gE proteins of HSV-1, which are associated with viral fusion and immune escape, to design a trivalent antigen vaccine that is capable of inducing a cellular immune response. Two formulations of the vaccine are available: a subunit vaccine incorporating oligodeoxynucleotides with CpG motifs (CpG ODNs) and QS-21 as adjuvants, as well as an mRNA vaccine. Mice were immunized via intramuscular injection to evaluate and compare the immunological responses and protective efficacy of the two vaccines. Results: After the challenge, the viral load in the tissues of both vaccine groups was significantly lower than that in the positive control group, indicating that both vaccines were able to control viral proliferation in the tissues. Conclusions: The findings indicated that both mRNA and subunit vaccines were capable of eliciting comparable humoral and cellular immune responses. Full article

Background: Sexually transmitted infections (STIs) are common globally, posing significant public health challenges and financial strain, especially in low- and middle-income countries. Sub-Saharan Africa (SSA) accounts for 40% of global STI prevalence, with South Africa having the highest rates of curable STIs and human immunodeficiency virus (HIV), both of which are closely linked to increasing HIV transmission risk and other STIs. Genital ulcer disease (GUD), primarily caused by HSV-1, HSV-2, and Treponema pallidum, and less frequently by Haemophilus ducreyi, Klebsiella granulomatis, and Chlamydia trachomatis, exemplifies the complex interplay of STIs. Methods: This study analyzed GUD and co-infection with HIV, testing patterns, and co-occurrence trends among public clinic attendees in Mthatha, South Africa, to identify demographic, behavioral, and occupational disparities. Results: Sex-specific analysis revealed higher HIV prevalence among female attendees (47.00%) compared to male attendees (22.00%), alongside notable testing gaps and disparities in diseases such as syphilis, genital herpes, and lymphogranuloma venereum (LGV). Age-specific trends indicated the highest HIV prevalence in individuals aged 30–49, with peaks at 66.67% (30–39) and 76.47% (40–49). Treponema pallidum and HSV-2 prevalence were most pronounced in younger age groups (<20 and 20–29), while older demographics (50+) exhibited significant diagnostic gaps. Occupation-based analysis highlighted elevated HIV (65.91%) and HSV-2 (19.61%) prevalence among unemployed individuals, reflecting socioeconomic vulnerabilities. Co-occurrence analysis revealed notable overlaps, such as HIV and HSV-2 (6.67%) and Chlamydia trachomatis with HSV-1 (5.71%) and HSV-2 (4.76%), driven by shared risk factors. Correlation analysis identified strong links between HSV-1 and Haemophilus ducreyi (0.64) and between Chlamydia trachomatis and HSV-1 (0.56), underscoring the potential for integrated diagnostic strategies. Conclusion: These findings emphasize the need for targeted public health interventions addressing sex, age, and occupational disparities while improving diagnostic coverage and prevention efforts for co-occurring infections. Full article

Vulvar viral infections such as condyloma acuminata, genital herpes, molluscum contagiosum, and Lipschütz ulcers span both sexually and non-sexually transmitted diseases and affect patients across all age groups. Lesions may present as papules, verrucous growths, or painful ulcers, often causing functional impairment and significant psychosocial distress. A multidisciplinary strategy that integrates epidemiology, precise diagnostics, individualized therapy, and psychological support is essential to optimize outcomes. We performed a structured literature search in PubMed, Scopus, and Web of Science using terms “vulvar viral infection,” “HPV,” “HSV,” “molluscum contagiosum,” and “Lipschütz ulcers.” International guidelines from the UK, Europe, and Australia were reviewed, alongside reference lists of key articles. Particular attention was given to paradoxical presentations, pediatric considerations, and cost-effectiveness analyses. HPV vaccination programs have markedly reduced anogenital warts, while early PCR/NAAT for HSV accelerates targeted antiviral therapy. First-line treatments like oral acyclovir/famciclovir for HSV and topical imiquimod or podophyllotoxin (±cryotherapy) for HPV are supported by adjunctive measures for self-limiting conditions. Host factors (hormonal cycles, immune status) and local irritants modulate recurrence risk, informing anticipatory suppressive regimens and barrier-reinforcing care. Validated patient-reported outcome measures (VPAQ, DLQI, FSFI) capture pain, sexual function, and quality-of-life impacts. Health–economic evaluations underscore the long-term value of rapid diagnostics and broad vaccination. Personalized, multidisciplinary management that combines prevention, precision diagnostics, tailored therapy, psychosocial support, and economic considerations offers the greatest promise for improving clinical and quality-of-life outcomes in patients with vulvar viral infections. We aim to outline best practices for the diagnosis and management of common vulvar viral infections, providing practical guidance for clinicians to improve recognition and therapeutic decision-making. Full article

The development of vaccines against many infectious diseases has been a great success of medical science over the last century. However, despite numerous efforts, effective vaccines for herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) remain elusive. Since 1920s, a range of therapeutic vaccine candidates, primarily focusing on neutralizing antibodies, have failed to confer robust and durable protective immunity against recurrent herpes. Recent advances in omics, artificial intelligence, and deep learning have opened new horizons for the rational design of tissue-targeted herpes vaccine strategies for inducing potent and durable HSV-specific CD4⁺ and CD8⁺ T_RM cell immunity at both the sensory ganglia (central immunity), the site of latency/reactivation cycle, and the mucocutaneous epithelial tissues (peripheral immunity), the site of viral replication that causes herpetic lesions. Prime/Pull/Keep ocular and genital herpes vaccine candidates (PPK vaccines) have recently shown success in pre-clinical animal model trials of recurrent ocular and genital herpes. These PPK vaccines used “asymptomatic” epitopes/antigens to prime CD4⁺ and CD8⁺ T cells (Prime); primed T cells are then pulled towards the infected central and peripheral epithelial tissues using T cell-attracting chemokines, such as CXCL11 (Pull), followed by survival cytokines (IL-2, IL-7 and/or IL-15) or mucosal chemokines (CXCL17 and/or CCL28) to maintain the “pulled” tissue-resident T cells longer within infected tissues (Keep). We discuss recent efforts in designing a clinically adapted, all-in-one PPK mucosal therapeutic vaccine that would require a single administration to sequentially trigger all three PPK steps of priming, recruiting, and maintaining antiviral, tissue-resident, protective T cells at the primary sites of viral entry and latency. Full article

Background and Aim: The immunological interactions between soil-transmitted helminths (STHs) and herpes simplex virus type 2 (HSV-2), particularly in the context of co-infection, are poorly understood. Next-generation sequencing (NGS) offers a powerful approach to explore these complex immune responses and uncover potential therapeutic targets. This study leveraged NGS and bioinformatic tools to investigate transcriptional changes and immunological pathways in female genital tract (FGT) tissues of BALB/c mice acutely infected with Nippostrongylus brasiliensis (Nb), HSV-2, or co-infected. Methods: Total RNA was harvested from FGT tissues of BALB/c mice infected with Nb, HSV-2, co-infected with both pathogens, and uninfected controls. Differentially expressed genes (DEGs) were identified by comparing uninfected versus infected FGT tissues in R using edgeR and limma packages. Immune-related genes were identified by intersecting DEGs in each group-wise comparison with immune function gene sets derived from the Mouse Genome Informatics (MGI) database. Functional and pathway enrichment analyses were performed with g: Profiler and protein–protein interaction networks were built using the STRING database and visualized with Cytoscape. Key hub genes and significant gene modules were identified using the Cytoscape plugins CytoHubba and MCODE, followed by further functional analysis of these modules. Results: NGS analysis revealed distinct gene expression profiles in response to single infection with Nb or HSV-2, with both showing significant differences when uninfected controls were compared to infected FGT tissues at a 5% false discovery rate. Notably, there were no significant differences in gene expression profiles between uninfected and co-infected FGT tissues. In the comparison of uninfected versus Nb-infected FGT tissues, 368 DEGs were identified, with 356 genes upregulated and 12 downregulated. Several immune-related genes, such as Ptprc, Ccl11, Ccr2, and Cx3cr1, were significantly altered. Pathway analysis of DEGs, hub genes, and significant modules indicated modulation of immune and defense responses. Notably, Nb infection induced a robust Th2-dominant immune response in the FGT, with downregulation of pro-inflammatory genes. This likely reflects helminth-driven modulation that may impair protective Th1 responses and highlights the systemic impact of Nb on the FGT immunity. In the comparison of uninfected versus HSV-2-infected FGT tissues, 140 DEGs were identified, with 121 upregulated and 19 downregulated. Immune-related genes, including Ldlr, Camk1d, Lrp8 and Epg5, were notably altered. HSV-2 infection led to early and predominant downregulation of immune genes, consistent with viral immune evasion strategies. In addition, functional analysis revealed enrichment in cell cycle and sterol biosynthesis pathways, suggesting that HSV-2 modulates host metabolism to support viral replication while influencing immune responses. In co-infection, no significant transcriptional changes were observed, potentially reflecting immune antagonism where Nb-induced Th2 responses may suppress HSV-2-driven Th1 immune responses. Conclusions: This preliminary study offers insights into the gene expression responses in the FGT to acute single and co-infection with Nb and HSV-2. Together, these findings reveal distinct transcriptomic changes in the FGT following Nb and HSV-2 infection, with co-infection potentially leading to immune antagonism and transcriptional equilibrium. This highlights the complex interplay between helminth- and virus-induced immune modulation in shaping FGT immunity. By leveraging NGS, this study highlights important immune-related pathways and serves as a foundation for further investigations into the mechanistic roles of DEGs in immunity to these pathogens, with potential implications for developing novel therapeutic strategies. Full article

Sexually transmitted infections (STIs) are a significant global health concern, affecting millions of people worldwide, particularly sexually active adolescents and young adults. These infections, caused by various pathogens, including bacteria, viruses, parasites, and fungi, can have profound implications for women’s reproductive health and fertility. This review explores the role of vaginal and uterine infections in women’s infertility, focusing on the most common pathogens and their impact on reproductive outcomes. Bacterial infections, such as those caused by intracellular bacteria (Mycoplasma, Ureaplasma, and Chlamydia), Neisseria gonorrhoeae, and bacterial vaginosis, are among the most prevalent causes of infertility in women. Studies have shown that these infections can lead to pelvic inflammatory disease, tubal occlusion, and endometrial damage, all of which can impair fertility. Mycobacterium tuberculosis, in particular, is a significant cause of genital tuberculosis and infertility in high-incidence countries. Viral infections, such as Human papillomavirus (HPV) and Herpes simplex virus (HSV), can also affect women’s fertility. While the exact role of HPV in female infertility remains unclear, studies suggest that it may increase the risk of endometrial implantation issues and miscarriage. HSV may be associated with unexplained infertility. Parasitic infections, such as trichomoniasis and schistosomiasis, can directly impact the female reproductive system, leading to infertility, ectopic pregnancy, and other complications. Fungal infections, such as candidiasis, are common but rarely have serious outcomes related to fertility. The vaginal microbiome plays a crucial role in maintaining reproductive health, and alterations in the microbial balance can increase susceptibility to STIs and infertility. Probiotics have been proposed as a potential therapeutic strategy to restore the vaginal ecosystem and improve fertility outcomes, although further research is needed to establish their efficacy. In conclusion, vaginal and uterine infections contribute significantly to women’s infertility, with various pathogens affecting the reproductive system through different mechanisms. Early diagnosis, appropriate treatment, and preventive measures are essential to mitigate the impact of these infections on women’s reproductive health and fertility. Full article

Soil-transmitted helminths (STHs) and Herpes Simplex Virus type 2 (HSV-2) are highly prevalent infections with overlapping distribution, particularly in resource-poor regions. STH/HSV-2 co-infections may impact female reproductive health. However, many aspects of STH/HSV-2 co-infections, including the role of microRNAs (miRNAs) in regulating female genital tract (FGT) immunity and their potential contribution to pathologies such as chronic inflammation, impaired mucosal defense, and reproductive tract cancers remain unclear. In this study we investigated the miRNA expression profiles in murine FGT tissues following single or co-infection with Nippostrongylus brasiliensis (Nb) and HSV-2 and explored predicted miRNA-mRNA targets and pathways. An analysis of miRNA sequencing data was conducted to determine differentially expressed (DE) miRNAs between infected FGT tissues and uninfected controls. Ingenuity Pathway Analysis was conducted to predict the immune-related target genes of the DE miRNAs and reveal enriched canonical pathways, top diseases, and biological functions. Selected representative DE miRNAs were validated using RT-qPCR. Our results showed a total of eight DE miRNAs (mmu-miR-218-5p, mmu-miR-449a-5p, mmu-miR-497a-3p, mmu-miR-144-3p, mmu-miR-33-5p, mmu-miR-451a, mmu-miR-194-5p, and mmu-miR-192-5p) in the comparison of Nb-infected versus uninfected controls; nine DE miRNAs (mmu-miR-451a, mmu-miR-449a-5p, mmu-miR-144-3p, mmu-miR-376a-3p, mmu-miR-192-5p, mmu-miR-218-5p, mmu-miR-205-3p, mmu-miR-103-3p, and mmu-miR-200b-3p) in the comparison of HSV-2-infected versus uninfected controls; and one DE miRNA (mmu-miR-199a-5p) in the comparison of Nb/HSV-2 co-infected versus uninfected controls (p-value < 0.05, |logFC| ≥ 1). Core expression analysis showed that, among other canonical pathways, the DE miRNAs and their predicted mRNA targets were involved in neutrophil degranulation, interleukin-4 and interleukin-13 signaling, natural killer cell signaling, interferon alpha/beta signaling, and ISGylation. Additionally, cancer was predicted as one of the significantly enriched diseases, particularly in the co-infected group. This is the first study to provide insights into the FGT miRNA profiles following Nb and HSV-2 single and co-infection, as well as the predicted genes and pathways they regulate, which may influence host immunity and pathology. This study highlights the role of miRNAs in regulating FGT immunity and pathology in the context of STH/HSV-2 co-infection. Full article

Background: The objective of this study is to investigate the prevalence and epidemiological changes of major sexually transmitted infections (STIs) in Korea over the past decade. Methods: From 2010 to 2021, patients diagnosed with STIs based on ICD-10 codes were analyzed using Korean Health insurance data. The analysis included the number of patients, prevalence, and age-specific prevalence (in 5-year intervals) over this period. We examined changes in disease patterns over time by analyzing the annual trends and age-specific prevalence of bacterial STIs such as chlamydia, mycoplasma, gonorrhea, and syphilis; viral STIs such as genital herpes, human papillomavirus (HPV), and human immunodeficiency virus (HIV); and other infections including scabies, pubic lice, and trichomoniasis. Results: In 2010, the STI with the highest prevalence due to an infectious pathogen was trichomoniasis (256.65/100,000), while latent syphilis had the lowest prevalence (5.29/100,000). In 2021, the STI with the highest prevalence was genital herpes (254.54 per 100,000 persons), and latent syphilis continued to have the lowest prevalence. Bacterial STIs showed a decreasing trend. Viral STIs showed a continuous increase throughout the study period, with anogenital warts (AGW) having the highest rate of increase. Other infections showed a decreasing trend. HIV and AGW in men showed a rapid increase. Gender differences varied depending on the disease. Conclusions: While bacterial STIs have gradually declined, viral STIs have continued to increase during last decade. The characteristics of each pathogen vary according to age and gender, necessitating the establishment of risk groups for each pathogen and the development of prevention policies accordingly. Full article

Herpes simplex virus (HSV) is a prevalent and persistent human pathogen belonging to the family Herpesviridae and classified as an alpha-herpesvirus. It comprises two distinct types, HSV-1 and HSV-2, which together infect a significant portion of the global population and pose substantial public health challenges. HSV-1 is typically associated with oral herpes, while HSV-2 primarily causes genital herpes; both are characterized by recurrent lesions, latent infection, and mucocutaneous discomfort. Conventional antiviral drugs such as acyclovir and its derivatives are limited by drug resistance, potential toxicity, and their inability to eradicate latent viral reservoirs. These limitations have prompted increasing interest in alternative therapeutic strategies. Phenolic acids and tannins, plant-derived polyphenolic compounds, have attracted considerable attention due to their potent antiviral properties against various viruses, including HSV. This review summarizes current research on phenolic acids and tannins as promising natural antivirals against HSV, with a focus on their mechanisms of action and efficacy in disrupting multiple stages of the HSV life cycle. Full article

Background: Female sex workers (FSWs) in sub-Saharan Africa bear a disproportionate burden of sexually transmitted infections, including HIV, high-risk HPV (HR-HPV), and herpes simplex virus type 2 (HSV-2). This study evaluated possible association between HR-HPV, HIV, and HSV-2 among FSWs in the Democratic Republic of the Congo. Methods: A cross-sectional study was conducted among 432 FSWs (mean age, 28.1 years) recruited via respondent-driven sampling. Genital self-sampling using the V-Veil UP2™ device was performed, followed by HPV genotyping and quantification by multiplex PCR, and HSV-2 DNA detection by PCR. Results: Among 415 participants, HR-HPV prevalence was 36.9%, with HPV-52 (14.9%), HPV-58 (10.1%), and HPV-16 (6.5%) as leading genotypes. Overall, 89% of HR-HPV-positive women harbored genotypes covered by Gardasil-9^®. Co-infection with HIV and HSV-2 significantly increased HPV prevalence, genotype diversity, and viral load. Notably, HSV-2 positivity was the sole independent predictor of elevated replication of HR-HPV (p < 0.001), vaccine HR-HPV (p < 0.001), and non-vaccine HR-HPV (p < 0.021). Conclusions: FSWs exhibit a high burden of HR-HPV, shaped by co-infections with HIV and HSV-2. HSV-2 independently drives HR-HPV replication, highlighting its role in HPV persistence and cervical cancer risk. Integrated HSV-2 detection and Gardasil-9^® vaccination should be prioritized in cervical cancer elimination strategies targeting high-risk populations in sub-Saharan Africa. Full article

Seroconversion is defined as a four-fold or greater rise in antibody titers. This assay is used in human prophylactic vaccine trials to confirm HSV as the cause of genital lesions and detect subclinical latent infection. We evaluated the accuracy of seroconversion in detecting infection using a guinea pig model of genital infection. Not all animals intravaginally inoculated with HSV-2 become infected, particularly if vaccinated; therefore, we need to establish criteria to determine whether an animal is infected. Our primary analysis involved considering animals to be infected if they had any of the following: (a) genital lesions; (b) HSV-2 DNA in vaginal secretions four or more weeks after HSV-2 inoculation as a marker of reactivation from latency; or (c) HSV-2 DNA in dorsal root ganglia, the site of latency. In the second analysis, we considered animals to be infected if they had positive virus cultures from vaginal swabs obtained on day two or four post HSV-2 inoculation. In the third analysis, we considered animals to be infected if they had any condition included in the first two analyses. We collected sera prior to HSV-2 inoculation and two months later and tested the first 57 animals for seroconversion using Western blotting and gG2 IgG ELISA. The results were concordant in 54 of 57 animals (95%), and when discordant, the gG2 ELISA matched infection results as defined by the primary analysis. The remaining animals were evaluated by gG2 IgG ELISA only. A total of 43 animals were inoculated with HSV-2 but not vaccinated (No vaccine group), and 224 were vaccinated with glycoprotein or mRNA vaccines prior to HSV-2 inoculation (Vaccine group). In the No vaccine group, we detected no false positives (seroconversion without infection) but 24% to 29% false negatives (no seroconversion despite infection) depending on the criteria used to define infection. In the Vaccine group, we detected 8% to 22% false positives and 31% to 37% false negatives. The accuracy of seroconversion was 74% to 79% in the No vaccine group and 71% to 76% in the Vaccine group. These results raise concerns about using seroconversion as a diagnostic test in human vaccine trials. Alternate approaches, such as subject home swabbing for HSV DNA, should be considered as a possible replacement. Full article

The general female population is not considered a high-risk group for screening for sexually transmitted infections (STIs). This retrospective study describes the prevalence of Human Immunodeficiency Virus (HIV), Treponema pallidum (T. pallidum), Chlamydia trachomatis (C. trachomatis), Neisseria gonorrhoeae (N. gonorrhoeae), Trichomonas vaginalis (T. vaginalis), Mycoplasma spp., Ureaplasma spp., genital Herpes simplex virus (HSV), Monkeypox (mpox), Hepatitis B virus (HBV), and Hepatitis C virus (HCV) infections in asymptomatic and symptomatic cisgender women attending our walk-in STI clinic for the first time. Furthermore, it analyzes the number of individuals who returned for follow-up and were diagnosed with new STIs. Over 20 months, 189 women with a median age of 28.4 years were screened [129 (68.3%) asymptomatic and 60 (31.8%) symptomatic]. In order of prevalence, the most common STIs were: Ureaplasma spp. infections (50.3%), C. trachomatis (10.6%), N. gonorrhoeae (5.8%), Mycoplasma hominis infections (5.8%), T. pallidum (2.65%), HSV2 infections (2.65%), and mpox (0.53%). No diagnosis of HIV, trichomoniasis, HBV, or HCV was registered. After the initial evaluation, 128 (67.7%) women returned for follow-up, but only 43 (22.8%) repeated screening; among them, 11 (25.6%) were diagnosed with new STIs. Given the high prevalence of STIs in cisgender women, awareness measures to improve screening and prevention strategies in this neglected population are required. Full article

Background: Herpes simplex virus 2 (HSV-2) is the primary cause of sexually transmitted genital ulcerative diseases, for which no effective prophylactic vaccine is currently available. However, the identification of appropriate targets for an HSV-2 mRNA vaccine remains an area requiring further investigation. Methods: The immunogenicity and protective effects of an HSV-2 UL41 mRNA vaccine were evaluated in a BALB/c mouse model. The mice were intramuscularly immunized twice, followed by HSV-2 infection at 28 days post boost. Clinical signs were monitored daily, and the viral load and tissue inflammation were assessed on days 1, 4, and 7 post infection. Dendritic cell (DC) activation in spleen tissue was analyzed via transcriptome sequencing. Results: A comparison of the clinical, immunological, and pathological characteristics of the groups that were immunized with the UL41 mRNA vaccine and then infected with HSV2, along with the control groups, revealed that the vaccine elicited both cellular and humoral immunity, inhibited viral replication, suppressed the inflammatory response, and provided protective effects against the virus in vivo. Furthermore, in vitro assays of DC expansion revealed that the vaccine immunization increased the induction of DCs from splenic cells. Transcriptomic analysis of these DCs revealed the activation of immune signaling pathways. Conclusions: Our study suggests that the UL41 mRNA vaccine may provide effective protection against HSV-2-related diseases and holds promise as a potential mRNA vaccine candidate. Full article