Norovirus Vaccine Research Articles

Lipid nanoparticles as adjuvant of norovirus VLP vaccine augment cellular and humoral immune responses in a TLR9- and type I IFN-dependent pathway.

Norovirus (NoV) virus-like particles (VLPs) adjuvanted with aluminum hydroxide (Alum) are common vaccine candidates in clinical studies. Alum adjuvants usually inefficiently assist recombinant proteins to induce cellular immune responses. Thus, novel adjuvants are required to develop NoV vaccines that could induce both efficient humoral and robust cellular immune responses. Lipid nanoparticles (LNPs) are well-known mRNA delivery vehicles. Increasing evidence suggests that LNPs may have intrinsic adjuvant activity and can be used as adjuvants for recombinant protein vaccines; however, the underlying mechanism remains poorly understood. In this study, we compared the adjuvant effect of LNPs and Alum for a bivalent GI.1/GII.4 NoV VLP vaccine. Compared with Alum, LNP-adjuvanted vaccines induced earlier production of binding, blocking, and neutralizing antibodies and promoted a more balanced IgG2a/IgG1 ratio. It is crucial that LNP-adjuvanted vaccines induced stronger Th1-type cytokine-producing CD4+ T cell and CD8+ T cell responses than Alum. The adjuvant activity of LNPs depended on the ionizable lipid components. Mechanistically, LNPs activated innate immune responses in a type I IFN-dependent manner and were partially dependent on Toll-like receptor (TLR) 9, thus affecting the adaptive immune responses of the vaccine. This conclusion was supported by RNA-seq analysis and in vitro cell experiments and by the deeply blunted T cell responses in IFNαR1-/- mice immunized with LNP-adjuvanted vaccines. This study not only identified LNPs as a high quality adjuvant for NoV VLP vaccines, but also clarified the underlying mechanism of LNPs as a potent immunostimulatory component for improving protein subunit vaccines.IMPORTANCEWith the rapid development of mRNA vaccines, recurrent studies show that lipid nanoparticles (LNPs) have adjuvant activity. However, the mechanism of its adjuvant effect in protein vaccines remains unknown. In this study, we found that the LNP-adjuvanted norovirus bivalent virus-like particle vaccines led to durable antibody responses as well as Th1-type cytokine-producing CD4+ T cell and CD8+ T cell responses, which exceeded the efficiency of the conventional adjuvant aluminum hydroxide. Mechanistically, LNPs activated innate immune responses in a type I IFN-dependent manner and were partially dependent on Toll-like receptor 9, thus affecting the adaptive immune responses of the vaccine. This work unveils that LNPs as a potent immunostimulatory component may be ideal for generating CD8+ T cell and B cell responses for recombinant protein vaccines.

Bivalent norovirus mRNA vaccine elicits cellular and humoral responses protecting human enteroids from GII.4 infection

Nucleoside-modified mRNA-LNP vaccines have revolutionized vaccine development against infectious pathogens due to their ability to elicit potent humoral and cellular immune responses. In this article, we present the results of the first norovirus vaccine candidate employing mRNA-LNP platform technology. The mRNA-LNP bivalent vaccine encoding the major capsid protein VP1 from GI.1 and GII.4 of human norovirus, generated high levels of neutralizing antibodies, robust cellular responses, and effectively protected human enteroids from infection by the most prevalent genotype (GII.4). These results serve as a proof of concept, demonstrating that a modified-nucleoside mRNA-LNP vaccine based on norovirus VP1 sequences can stimulate an immunogenic response in vivo and generates neutralizing antibodies capable of preventing viral infection in models of human gastrointestinal tract infection.

A quadrivalent norovirus vaccine based on a chimpanzee adenovirus vector induces potent immunity in mice

Norovirus (NoV) infection is a major cause of gastroenteritis worldwide. The virus poses great challenges in developing vaccines with broad immune protection due to its genetic and antigenic diversity. To date, there are no approved NoV vaccines for clinical use. Here, we aimed to develop a broad-acting quadrivalent NoV vaccine based on a chimpanzee adenovirus vector, AdC68, carrying the major capsid protein (VP1) of noroviral GI and GII genotypes. Compared to intramuscular (i.m.), intranasal (i.n.), or other prime-boost immunization regimens (i.m. ​+ ​i.m., i.m. ​+ ​i.n., i.n. ​+ ​i.m.), AdC68-GI.1-GII.3 (E1)-GII.4-GII.17 (E3), administered via i.n. ​+ ​i.n. induced higher titers of serum IgG antibodies and higher IgA antibodies in bronchoalveolar lavage fluid (BALF) and saliva against the four homologous VP1s in mice. It also significantly stimulated the production of blocking antibodies against the four genotypes. In response to re-stimulation with virus-like particles (VLP)-GI.1, VLP-GII.3, VLP-GII.4, and VLP-GII.17, the quadrivalent vaccine administered according to the i.n. ​+ ​i.n. regimen effectively triggered specific cell-mediated immune responses, primarily characterized by IFN-γ secretion. Furthermore, the preparation of this novel quadrivalent NoV vaccine requires only a single recombinant adenovirus to provide broad preventive immunity against the major GI/GII epidemic strains, making it a promising vaccine candidate for further development.

GI.1 Norovirus Neutralizing Antibody Levels Are Correlated with GI.1 Histo-blood Group Antigen-Blocking Antibody Levels.

The in vitro cultivation of human noroviruses allows a comparison of antibody levels measured in neutralization and histoblood group antigen (HBGA)-blocking assays. Serum samples collected during the evaluation of an investigational norovirus vaccine (HIL-214 [formerly TAK-214]) were assayed for neutralizing antibody levels against the vaccine's prototype Norwalk virus/GI.1 (P1) virus strain. Results were compared to those previously determined using HBGA-blocking assays. Neutralizing antibody seroresponses were observed in 83% of 24 vaccinated adults, and antibody levels were highly correlated (r=0.81, P<0.001) with those measured by HBGA-blocking. GI.1-specific HBGA-blocking antibodies are a surrogate for neutralization of GI.1 norovirus.

GII.6 norovirus major capsid protein VP1 derived from distinct clusters induce cross-blocking effects

Unlike pandemic GII.4 norovirus, GII.6 norovirus shows limited sequence variation in its major capsid protein VP1. In this study, we investigated the VP1 expression profiles, binding abilities, and cross-blocking effects of three GII.6 norovirus strains derived from three distinct variants. Norovirus VP1 was expressed using a recombinant baculovirus expression system and characterized by transmission electron microscopy, mass spectrometry, salivary histo-blood group antigen (HBGA)-virus like particles (VLPs) binding and binding blockade assays. Mass spectrometry revealed the expected molecular weight (MW) of full-length proteins and degraded or cleaved fragments of all three VP1 proteins. Peptide mapping showed loss of 2 and 3 amino acids from the N- and C-terminus, respectively. Further, the co-expression of VP1 and VP2 proteins did not lead to extra fragmentation during mass spectrometry. Salivary HBGA-VLP binding assay revealed similar binding patterns of the three GII.6 VP1 proteins. Salivary HBGA-VLP binding blockade assay induced cross-blocking effects. Our results demonstrate similar binding abilities against salivary HBGAs and specific cross-blocking effects for GII.6 norovirus strains derived from distinct variants, suggesting that fewer GII.6 strains from different evolutionary variants are needed for the development of norovirus vaccines.

Noroviruses: Evolutionary Dynamics, Epidemiology, Pathogenesis, and Vaccine Advances-A Comprehensive Review.

Noroviruses constitute a significant aetiology of sporadic and epidemic gastroenteritis in human hosts worldwide, especially among young children, the elderly, and immunocompromised patients. The low infectious dose of the virus, protracted shedding in faeces, and the ability to persist in the environment promote viral transmission in different socioeconomic settings. Considering the substantial disease burden across healthcare and community settings and the difficulty in controlling the disease, we review aspects related to current knowledge about norovirus biology, mechanisms driving the evolutionary trends, epidemiology and molecular diversity, pathogenic mechanism, and immunity to viral infection. Additionally, we discuss the reservoir hosts, intra-inter host dynamics, and potential eco-evolutionary significance. Finally, we review norovirus vaccines in the development pipeline and further discuss the various host and pathogen factors that may complicate vaccine development.

Health Care Utilization and Clinical Management of All-Cause and Norovirus-Associated Acute Gastroenteritis Within a US Integrated Health Care System.

Norovirus-associated acute gastroenteritis (AGE) exacts a substantial disease burden, yet the health care utilization for and clinical management of norovirus-associated AGE are not well characterized. We describe the health care encounters and therapeutics used for patients with all-cause and norovirus-associated AGE in the Kaiser Permanente Northwest health system from 1 April 2014 through 30 September 2016. Medical encounters for patients with AGE were extracted from electronic health records, and encounters within 30 days of one another were grouped into single episodes. An age-stratified random sample of patients completed surveys and provided stool samples for norovirus testing. In total, 40 348 individuals had 52 509 AGE episodes; 460 (14%) of 3310 participants in the substudy tested positive for norovirus. An overall 35% of all-cause AGE episodes and 29% of norovirus-associated AGE episodes had ≥2 encounters. While 80% of norovirus-associated AGE episodes had at least 1 encounter in the outpatient setting, all levels of the health care system were affected: 10%, 22%, 10%, and 2% of norovirus-associated AGE episodes had at least 1 encounter in virtual, urgent care, emergency department, and inpatient settings, respectively. Corresponding proportions of therapeutic use between norovirus-positive and norovirus-negative episodes were 13% and 10% for intravenous hydration (P = .07), 65% and 50% for oral rehydration (P < .001), 7% and 14% for empiric antibiotic therapy (P < .001), and 33% and 18% for antiemetics (P < .001). Increased health care utilization and therapeutics are likely needed for norovirus-associated AGE episodes during peak norovirus winter seasons, and these data illustrate that effective norovirus vaccines will likely result in less health care utilization.

Transmission Patterns of Norovirus From Infected Children to Household Members in León, Nicaragua.

Norovirus is a common and highly transmissible gastrointestinal pathogen. Among 34 Nicaraguan households with a norovirus-infected child, 48% experienced norovirus transmission within 1 week, infecting 18% of household members; GII norovirus was more commonly transmitted than GI. Pediatric norovirus vaccines could prevent both index cases and transmission to close contacts.

Human norovirus cultivation models, immune response and vaccine landscape.

Norovirus infections are a leading cause of gastroenteritis worldwide. Despite the substantial global health burden and economic impact, there are currently no approved antiviral therapeutics or vaccines. Additionally, much of our knowledge of norovirus comes from experiments using surrogate viruses, such as murine norovirus and feline calicivirus. The challenge surrounding human norovirus research arises from a lack of robust cell culture systems and efficient animal models. In this review, we explore recent advances in the in vitro cultivation of human norovirus and reverse genetics systems and discuss commonly used in vivo models. We summarize the current understanding of both innate and adaptive immune responses to norovirus infection and provide an overview of vaccine strategies and the current clinical trial landscape, with a focus on the only vaccine candidate that has reached phase III clinical development stage.

UK's first potential norovirus vaccine to be trialled by UK government partnership with Moderna

UK's first potential norovirus vaccine to be trialled by UK government partnership with Moderna

Vaccine value profile for norovirus

Norovirus is attributed to nearly 1 out of every 5 episodes of diarrheal disease globally and is estimated to cause approximately 200,000 deaths annually worldwide, with 70,000 or more among children in developing countries. Noroviruses remain a leading cause of sporadic disease and outbreaks of acute gastroenteritis even in industrialized settings, highlighting that improved hygiene and sanitation alone may not be fully effective in controlling norovirus. Strengths in global progress towards a Norovirus vaccine include a diverse though not deep pipeline which includes multiple approaches, including some with proven technology platforms (e.g., VLP-based HPV vaccines). However, several gaps in knowledge persist, including a fulsome mechanistic understanding of how the virus attaches to human host cells, internalizes, and induces disease.

Biological and physico-chemical characterization of human norovirus-like particles under various environmental conditions

Human noroviruses (HuNoVs) are the predominant etiological agent of viral gastroenteritis in all age groups worldwide. Mutations over the years have affected noroviruses' responses to environmental conditions due to the arrangement of amino acid residues exposed on the VP1 capsid surface of each strain. The GII.4 HuNoV genotype has been the predominant variant for decades, while the GII.17 genotype has often been detected in East Asia since 2014. Here, GII.17 and GII.4 baculovirus-expressed VLPs (virus-like particles) were used to study the biological (binding to HuNoV ligand, namely the ABO and Lewis antigens) and physicochemical properties (size, morphology, and charge) of the HuNoV capsid under different conditions (temperature, pH, and ionic strength). GII.17 showed stability at low and high ionic strength, while GII.4 aggregated at an ionic strength of 10 mM. The nature of the buffers influences the morphology and stability of the VLPs. Here, both VLPs were highly stable from pH 7–8.5 at 25 °C. VLPs retained HBGA binding capability for the pH, ionic strength and temperature encountered in the stomach (fed state) and the small intestine. Increasing the temperature to above 65 °C altered the morphology of VLPs, causing aggregation, and decreased their affinity to HBGAs. Comparing both isolates, GII.17 showed a better stability profile and higher affinity to HBGAs than GII.4, making them interesting candidate particles for a future norovirus vaccine. Biological and physicochemical studies of VLPs are as pertinent as ever in view of the future arrival of VLP-based HuNoV vaccines.

Unraveling the interplay between norovirus infection, gut microbiota, and novel antiviral approaches: a comprehensive review.

Norovirus infection is a leading cause of acute gastroenteritis worldwide and can also cause harmful chronic infections in individuals with weakened immune systems. The role of the gut microbiota in the interactions between the host and noroviruses has been extensively studied. While most past studies were conducted in vitro or focused on murine noroviruses, recent research has expanded to human noroviruses using in vivo or ex vivo human intestinal enteroids culture studies. The gut microbiota has been observed to have both promoting and inhibiting effects on human noroviruses. Understanding the interaction between noroviruses and the gut microbiota or probiotics is crucial for studying the pathogenesis of norovirus infection and its potential implications, including probiotics and vaccines for infection control. Recently, several clinical trials of probiotics and norovirus vaccines have also been published. Therefore, in this review, we discuss the current understanding and recent updates on the interactions between noroviruses and gut microbiota, including the impact of norovirus on the microbiota profile, pro-viral and antiviral effects of microbiota on norovirus infection, the use of probiotics for treating norovirus infections, and human norovirus vaccine development.

Extracellular Production of the Taiwan-Native Norovirus P Domain Overexpressed in Pichia pastoris

Many efforts in norovirus vaccine development have focused on subunit or recombinant protein vaccines, such as subviral P particles formed by the protruding (P) domain of VP1. P particles are immunogenic and have a region with a human histo-blood group antigen binding site, an interaction critical for infecting the host. In the past, only intracellular NoV P proteins expressed in Escherichia coli and Pichia pastoris were reported, and the low yield and difficulty in purification limited their applications. In this study, the Taiwan-native NoV P domain was successfully expressed and secreted by P. pastoris. The secretion efficiency was greatly enhanced by integrating oligosaccharyl transferase (Ost1) into the α-factor signal peptide and coexpressing Hac1. The production of NoV P in fermentation cultures reached 345 mg/L, and the purity and recovery were 94.8% and 66.9%, respectively, after only ion-exchange chromatography. Transmission electron microscopy analysis showed that the small P particles were mostly ring-, square-, and triangle-shaped, with diameters of 10-15 nm. The biological activity of NoV P was confirmed by saliva-binding assay using human histo-blood group antigen. This study describes the secretion and characterization of the Taiwan-native norovirus P domain in P. pastoris. Particles formed from the P domain were similar in size, morphology, and binding ability to those expressed intracellularly. The strategy described in this study provides great potential in scale-up production and antiviral vaccine development.

Immunoinformatics-guided design of a multi-valent vaccine against Rotavirus and Norovirus (ChRNV22)

Rotavirus (RV) and Norovirus (NV) are the main viral etiologic agents of acute gastroenteritis (AG), a serious pediatric condition associated with significant death rates and long-term complications. Anti-RV vaccination has been proved efficient in the reduction of severe AG worldwide, however, the available vaccines are all attenuated and have suboptimal efficiencies in developing countries, where AG leads to substantial disease burden. On the other hand, no NV vaccine has been licensed so far. Therefore, we used immunoinformatics tools to develop a multi-epitope vaccine (ChRNV22) to prevent severe AG by RV and NV. Epitopes were predicted against 17 prevalent genotypes of four structural proteins (NV's VP1, RV's VP4, VP6 and VP7), and then assembled in a chimeric protein, with two small adjuvant sequences (tetanus toxin P2 epitope and a conserved sequence of RV's enterotoxin, NSP4). Simulations of the immune response and interactions with immune receptors indicated the immunogenic properties of ChRNV22, including a Th1-biased response. In silico search for putative host-homologous, allergenic and toxic regions also indicated the vaccine safety. In summary, we developed a multi-epitope vaccine against different NV and RV genotypes that seems promising for the prevention of severe AG, which will be further assessed by in vivo tests.

Immunogenicity and tolerability of a bivalent virus-like particle norovirus vaccine candidate in children from 6 months up to 4 years of age: A phase 2 randomized, double-blind trial

ABSTRACT We conducted a dose-finding phase 2 study of the HilleVax bivalent virus-like particle (VLP) vaccine candidate (HIL-214) in two cohorts of children, 6–≤12 months and 1–≤4 years of age (N = 120 per cohort), in Panama and Colombia (ClinicalTrials.gov, identifier NCT02153112). On Day 1, children randomized to one of the four equal groups received intramuscular injections of four different HIL-214 formulations containing 15/15, 15/50, 50/50, or 50/150 μg of GI.1/GII.4c genotype VLPs and 0.5 mg Al(OH)3. On Day 29, half the children in each group received a second vaccination (N = 60), while the other half received saline placebo injections to maintain the blind. VLP-specific ELISA Pan-Ig and histo-blood group binding antigen-blocking antibodies (HBGA) were measured on Days 1, 29, 57 and 210. On Day 29, after one dose, there were large Pan-Ig and HBGA responses in both age cohorts with some indication of dose-dependence, and higher geometric mean titers (GMT) in the older children. A further increase in titers was observed 28 days after a second dose in the 6–≤12-month-old groups, but less so in the 1–≤4-year-old groups; GMTs at Day 57 were broadly similar across doses and in both age groups. GMTs of Pan-Ig and HBGA persisted above baseline up to Day 210. All formulations were well tolerated with mostly mild-to-moderate transient solicited adverse events reported by parents/guardians, and no vaccine-related serious adverse events occurred. Further development of HIL-214 is warranted to protect the most susceptible young children against norovirus.

Generation of Recombinant Rotaviruses Expressing Human Norovirus Capsid Proteins.

Rotavirus, a segmented double-stranded RNA virus of the Reoviridae family, is a primary cause of acute gastroenteritis in young children. In countries where rotavirus vaccines are widely used, norovirus (NoV) has emerged as the major cause of acute gastroenteritis. Towards the goal of creating a combined rotavirus-NoV vaccine, we explored the possibility of generating recombinant rotaviruses (rRVs) expressing all or portions of the NoV GII.4 VP1 capsid protein. This was accomplished by replacing the segment 7 NSP3 open reading frame with a cassette encoding, sequentially, NSP3, a 2A stop-restart translation element, and all or portions (P, P2) of NoV VP1. In addition to successfully recovering rRVs with modified SA11 segment 7 RNAs encoding NoV capsid proteins, analogous rRVs were recovered through modification of the segment 7 RNA of the RIX4414 vaccine strain. An immunoblot assay confirmed that rRVs expressed NoV capsid proteins as independent products. Moreover, VP1 expressed by rRVs underwent dimerization and was recognized by conformational-dependent anti-VP1 antibodies. Serially passaged rRVs that expressed the NoV P and P2 were genetically stable, retaining additional sequences of up to 1.1 kbp without change. However, serially passaged rRVs containing the longer 1.6-kb VP1 sequence were less stable and gave rise to virus populations with segment 7 RNAs lacking VP1 coding sequences. Together, these studies suggest that it may be possible to develop combined rotavirus-NoV vaccines using modified segment 7 RNA to express NoV P or P2. In contrast, development of potential rotavirus-NoV vaccines expressing NoV VP1 will need additional efforts to improve genetic stability. IMPORTANCE Rotavirus (RV) and norovirus (NoV) are the two most important causes of acute viral gastroenteritis (AGE) in infants and young children. While the incidence of RV AGE has been brought under control in many countries through the introduction of universal mass vaccination with live attenuated RV vaccines, similar highly effective NoV vaccines are not available. To pursue the development of a combined RV-NoV vaccine, we examined the potential of using RV as an expression vector of all or portions of the NoV capsid protein VP1. Our results showed that by replacing the NSP3 open reading frame in RV genome segment 7 RNA with a coding cassette for NSP3, a 2A stop-restart translation element, and VP1, recombinant RVs can be generated that express NoV capsid proteins. These findings raise the possibility of developing new generations of RV-based combination vaccines that provide protection against a second enteric pathogen, such as NoV.

Epidemiology of Norovirus in the First 2 Years of Life in an Australian Community-based Birth Cohort.

Noroviruses are a leading cause of acute gastroenteritis across all age groups in Australia. We explored the epidemiology of symptomatic and asymptomatic norovirus infection and assessed risk factors and the related healthcare burden in Australian children during their first 2 years of life. Participants in the Observational Research in Childhood Infectious Diseases birth cohort provided weekly stool swabs, daily gastrointestinal symptoms (vomiting and loose stools) observations and healthcare data. Swabs were batch-tested for norovirus genogroups (GI and GII) using real-time polymerase chain reaction assays. Overall, 158 children returned 11,124 swabs. There were 221 infection episodes, of which 183 (82.8%) were GII. The incidence rate was 0.90 infections per child-year [95% confidence interval (CI): 0.74-1.09]. The symptomatic infection incidence rate was 0.39 per child-year (95% CI: 0.31-0.48), peaking between ages 6 and 11 months [0.58 (95% CI: 0.41-0.81)]. Incidence increased significantly with age and childcare attendance. Of 209 episodes with symptom diary data, 82 (39.2%) were symptomatic; of these 70 (85.4%) were associated with vomiting and 29 (35.4%) with diarrhea. Forty-one percent of symptomatic episodes required healthcare, including 4 emergency department presentations and 1 hospitalization. Children with initial infections had almost twice the risk of seeking primary healthcare compared to subsequent infections (adjusted risk ratio 1.92; 95% CI: 1.01-3.65). Norovirus infections, particularly GII, are common in Australian children 6-23 months of age. Estimates of norovirus incidence, including symptomatic infections and healthcare utilization in community settings in young children, are crucial for planning norovirus vaccine programs and determining vaccine effectiveness.

Norovirus Infection in Young Nicaraguan Children Induces Durable and Genotype-Specific Antibody Immunity.

There are significant challenges to the development of a pediatric norovirus vaccine, mainly due to the antigenic diversity among strains infecting young children. Characterizing human norovirus serotypes and understanding norovirus immunity in naïve children would provide key information for designing rational vaccine platforms. In this study, 26 Nicaraguan children experiencing their first norovirus acute gastroenteritis (AGE) episode during the first 18 months of life were investigated. We used a surrogate neutralization assay that measured antibodies blocking the binding of 13 different norovirus virus-like particles (VLPs) to histo-blood group antigens (HBGAs) in pre- and post-infection sera. To assess for asymptomatic norovirus infections, stools from asymptomatic children were collected monthly, screened for norovirus by RT-qPCR and genotyped by sequencing. Seroconversion of an HBGA-blocking antibody matched the infecting genotype in 25 (96%) of the 26 children. A subset of 13 (50%) and 4 (15%) of the 26 children experienced monotypic GII and GI seroconversion, respectively, strongly suggesting a type-specific response in naïve children, and 9 (35%) showed multitypic seroconversion. The most frequent pairing in multitypic seroconversion (8/12) were GII.4 Sydney and GII.12 noroviruses, both co-circulating at the time. Blocking antibody titers to these two genotypes did not correlate with each other, suggesting multiple exposure rather than cross-reactivity between genotypes. In addition, GII titers remained consistent for at least 19 months post-infection, demonstrating durable immunity. In conclusion, the first natural norovirus gastroenteritis episodes in these young children were dominated by a limited number of genotypes and induced responses of antibodies blocking binding of norovirus VLPs in a genotype-specific manner, suggesting that an effective pediatric norovirus vaccine likely needs to be multivalent and include globally dominant genotypes. The duration of protection from natural infections provides optimism for pediatric norovirus vaccines administered early in life.

Optimal control theory of a novel stochastic human norovirus model and vaccine development

Norovirus is a contagious disease that causes diarrhea and vomiting and has a significant impact on humanity in terms of medical costs, deaths and mortalities. In this research work, the stochastic modeling techniques are utilized and a novel human norovirus model is investigated keeping in view the contamination of food and water with vaccination effects. It is proved that the model has a unique global solution and by using Lyapunov function theory, sufficient conditions are derived under which the proposed model has a unique ergodic stationary distribution for [Formula: see text]. It is observed that the disease will extinct out of the population whenever [Formula: see text]. To demonstrate the analytical results, two independent examples are depicted graphically by using standard numerical algorithm. To reduce the spread of the virus, we employed certain control measures and an optimal control problem is presented. To further validate the obtained analytical results, additional graphical solutions were generated. This study might provide a robust theoretical framework for a global understanding of chronic communicable illnesses. Our method also aims to provide a method for producing Lyapunov functions, which can be used to explore the stationary distribution of disease models having nonlinear stochastic perturbations.