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Crimean-Congo hemorrhagic fever virus (CCHFV) is a zoonotic, tick-borne pathogen that is endemic to some parts of Europe, Africa, and Asia. The disease causes fever and hemorrhagic manifestations in humans but not in animals. Domestic and wild animals are asymptomatic hosts of CCHFV and are critical in the transmission cycle. Hyalomma marginatum spp. has been identified as the natural reservoir and vector of the virus in Turkiye. A few studies have been conducted on domesticated animals showing the seroprevalence of CCHFV in them, but seroevidence in wild animals is absent. For contributing this antrum to the understanding of virus transmission in Turkiye, we performed a seroprevalence investigation of CCHFV in both wild and domesticated animals in various geographical areas of Turkiye. In-house IgG iELISA was performed for the screening of sera IgG in a total of 582 animal samples collected from boar (n = 40), cattle (n = 259), goat (n = 132), hare (n = 21), and sheep (n = 130). Results from ELISA performed on domestic animals revealed 10.81%, 15.15%, and 19.23% anti-CCHF virus seropositivity in cattle, goats, and sheep, respectively, in collected serum samples. ELISA tests performed in wild animals showed 23.81% and 2.5% positivity in hare and wild boars, respectively, suggesting the importance of wild animals in CCHF virus epidemiology in Turkiye. This study performed the first serological investigation of CCHFV in wild animals and provided the first seroevidence of CCHFV in wild boars and hare in Turkiye.

This study- a secondary analysis of data from a randomized, observer-blinded, non-inferiority study among volunteers between 18–55 y old in Türkiye- evaluated the impact of previous SARS-CoV-2 infection before the first dose of inactive TURKOVAC on post-vaccine local and systemic adverse events (AEs) comparing with CoronaVac. Of 1266 participants analyzed, 27.7% had a previous COVID-19 history. Local and systemic AEs were observed in 37.3% and 39% of the participants. The frequency of AEs was slightly higher in the first 30 minutes and 24 hours among participants with a COVID-19 history; none were severe. 1203 participants had a second dose vaccination, and 27.3% had a history of COVID-19. The frequencies of local and systemic AEs after the second dose were similar between those with and without a COVID-19 history. The TURKOVAC and CoronaVac showed similar frequencies of local and systemic AEs in the first 30 minutes after vaccination.

Abstract Background Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus of the genus Nairovirus family Bunyaviridae, which are enveloped viruses containing tripartite, negative polarity, single-stranded RNA. CCHF is characterized by high case mortality, occurring in Asia, Africa, the Middle East and Europe. Currently, there are no specific treatments or licensed vaccines available for CCHFV. Recently, two research groups have found adult mice with defective interferon responses allowed to lethal CCHFV infection. These mouse models could provide invaluable information for further studies. Efforts to develop a vaccine against CCHFV are being made. To determine the efficacy of vaccine candidates it is important to conduct serological studies that can accurately measure levels of protective antibodies. In the present study, a pseudo-plaque reduction neutralization test (PPRNT) based on enzyme-catalyzed color development of infected cells probed with anti-CCHFV antibodies was used to measure neutralization antibody of CCHFV. Methods Sixty-nine human serum samples (20 acute and 49 convalescent) were tested. The presence of CCHFV antibodies was determined and confirmed by a commercial ELISA kit. CCHFV RNA was determined by RT-PCR. All the samples were analyzed by PPRNT and fluorescent focus reduction neutralization test (FFRNT) to measure of CCHFV-neutralizing antibodies. Results Pseudo-plaque reduction neutralization test showed a high sensitivity (98%), specificity (100%) and agreement (96,6%) in qualitative comparison with those of the FFRNT. There was a high correlation between the titers obtained in PPRNT and FFRNT (R2 = 0.92). The inter- and intra-assay variation of PPRNT revealed good reproducibility and positive cut-off of PPRNT was defined as 1:4 by the geometric mean titers for the individual samples distributed. Conclusion The pseudo-plaque reduction neutralization test described in this study is a fast, reproducible and sensitive method for the measurement of CCHF neutralizing antibodies. This novel assay could serve as useful tools for CCHF research in epidemiology, vaccine development and other studies of immunity. It also provides an alternative to PRNT when viruses with no or poor CPE in cell culture.

Vaccine-induced immunity wanes over time and warrants booster doses. We investigated the long-term (32 weeks) immunogenicity and safety of a third, homologous, open-label booster dose of TURKOVAC, administered 12 weeks after completion of the primary series in a randomized, controlled, double-blind, phase 2 study. Forty-two participants included in the analysis were evaluated for neutralizing antibodies (NAbs) (with microneutralization (MNT50) and focus reduction (FRNT50) tests), SARS-CoV-2 S1 RBD (Spike S1 Receptor Binding Domain), and whole SARS-CoV-2 (with ELISA) IgGs on the day of booster injection and at weeks 1, 2, 4, 8, 16, 24, and 32 thereafter. Antibody titers increased significantly from week 1 and remained higher than the pre-booster titers until at least week 4 (week 8 for whole SARS-CoV-2) (p < 0.05 for all). Seroconversion (titers ≥ 4-fold compared with pre-immune status) persisted 16 weeks (MNT50: 6-fold; FRNT50: 5.4-fold) for NAbs and 32 weeks for S1 RBD (7.9-fold) and whole SARS-CoV-2 (9.4-fold) IgGs. Nine participants (20.9%) tested positive for SARS-CoV-2 RT-PCR between weeks 8 and 32 of booster vaccination; none of them were hospitalized or died. These findings suggest that boosting with TURKOVAC can provide effective protection against COVID-19 for at least 8 weeks and reduce the severity of the disease.

The rapid spread of SARS-CoV-2 with its mutating strains has posed a global threat to safety during this COVID-19 pandemic. Thus far, there are 123 candidate vaccines in human clinical trials and more than 190 candidates in preclinical development worldwide as per the WHO on 1 October 2021. The various types of vaccines that are currently approved for emergency use include viral vectors (e.g., adenovirus, University of Oxford/AstraZeneca, Gamaleya Sputnik V, and Johnson & Johnson), mRNA (Moderna and Pfizer-BioNTech), and whole inactivated (Sinovac Biotech and Sinopharm) vaccines. Amidst the emerging cases and shortages of vaccines for global distribution, it is vital to develop a vaccine candidate that recapitulates the severe and fatal progression of COVID-19 and further helps to cope with the current outbreak. Hence, we present the preclinical immunogenicity, protective efficacy, and safety evaluation of a whole-virion inactivated SARS-CoV-2 vaccine candidate (ERUCoV-VAC) formulated in aluminium hydroxide, in three animal models, BALB/c mice, transgenic mice (K18-hACE2), and ferrets. The hCoV-19/Turkey/ERAGEM-001/2020 strain was used for the safety evaluation of ERUCoV-VAC. It was found that ERUCoV-VAC was highly immunogenic and elicited a strong immune response in BALB/c mice. The protective efficacy of the vaccine in K18-hACE2 showed that ERUCoV-VAC induced complete protection of the mice from a lethal SARS-CoV-2 challenge. Similar viral clearance rates with the safety evaluation of the vaccine in upper respiratory tracts were also positively appreciable in the ferret models. ERUCoV-VAC has been authorized by the Turkish Medicines and Medical Devices Agency and has now entered phase 3 clinical development (NCT04942405). The name of ERUCoV-VAC has been changed to TURKOVAC in the phase 3 clinical trial.

The COVID-19 pandemic has put global public health at high risk, rapidly spreading around the world. Although several COVID-19 vaccines are available for mass immunization, the world still urgently needs highly effective, reliable, cost-effective, and safe SARS-CoV-2 coronavirus vaccines, as well as antiviral and therapeutic drugs, to control the COVID-19 pandemic given the emerging variant strains of the virus. Recently, we successfully produced receptor-binding domain (RBD) variants in the Nicotiana benthamiana plant as promising vaccine candidates against COVID-19 and demonstrated that mice immunized with these antigens elicited a high titer of RBD-specific antibodies with potent neutralizing activity against SARS-CoV-2. In this study, we engineered the nucleocapsid (N) protein and co-expressed it with RBD of SARS-CoV-2 in Nicotiana benthamiana plant to produce an antigen cocktail. The purification yields were about 22 or 24 mg of pure protein/kg of plant biomass for N or N+RBD antigens, respectively. The purified plant produced N protein was recognized by N protein-specific monoclonal and polyclonal antibodies demonstrating specific reactivity of mAb to plant-produced N protein. In this study, for the first time, we report the co-expression of RBD with N protein to produce a cocktail antigen of SARS-CoV-2, which elicited high-titer antibodies with potent neutralizing activity against SARS-CoV-2. Thus, obtained data support that a plant-produced antigen cocktail, developed in this study, is a promising vaccine candidate against COVID-19.

Human toxocariasis is commonly seen in places where stray and Toxocara canis-infected dog population is high. There is a strong correlation between frequency of Toxocara infection, life style, and infection risk. Institutionalization of mental retarded patients increases to risk of toxocariasis. In this study, we aimed at investigating the frequency of Toxocara infection among children with mental retardation not requiring institutionalization. The study included 96 cases, who had educatable mental retardation and 85 healthy subjects who comprised the control group. Anti-Toxocara IgG or IgM antibodies were investigated in all serum samples, using ELISA method. The frequency of Toxocara infection was found significantly higher in mental retarded cases than in those in the control group (18.8% and 7.1% respectively) (p < 0.05). There was no significant difference between mental retarded children and the control group in terms of mean age, age groups, gender, owning dogs and cats and duration of their ownership, socio-economic level and behavioural factors, and personal hygiene (p > 0.05). We did not find any significant difference between Toxocara seropositive and seronegative mental retarded children in terms of demographic factors and epidemiological factors that could increase the risk of Toxocara infection (p > 0.05). The present study is the first seroprevalence study carried out with a mental retarded group not requiring institutionalization. Determination of high frequency of Toxocara infection suggests that these subjects constitute a risk factor for Toxocara infection, which may be attributed to their behavioural patterns.

SARS-CoV-2, the virus responsible for the COVID-19 pandemic, belongs to the betacoronavirus genus. This virus has a high mutation rate, which rapidly evolves into new variants with different properties, such as increased transmissibility or immune evasion. Currently, the most prevalent global SARS-CoV-2 variant is Omicron, which is more transmissible than previous variants. Current available vaccines may be less effective against some currently existing SARS-CoV-2 variants, including the Omicron variant. The S1 subunit of the spike protein of SARS-CoV-2 has been a major target for COVID-19 vaccine development. It plays a crucial role in the virus’s entry into host cells and is the primary target for neutralizing antibodies. In this study, the S1 subunit of the spike protein of SARS-CoV-2 was engineered and produced at a high level in Nicotiana benthamiana plant. The expression level of the recombinant S1 protein was greater than the 0.5-g/kg fresh weight, and the purification yield was at least ~0.3 g of pure protein/kg of plant biomass, which would make a plant-produced S1 antigen an ideal vaccine candidate for commercialization. Purified, the plant-produced SARS-CoV-2 S1 protein exhibited significantly higher binding to the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2). Moreover, we also show that recombinant S1 protein/antigen-elicited antibodies can neutralize the Delta or Omicron variants. Collectively, our results demonstrate that a plant-produced S1 antigen could be a promising vaccine candidate against SARS-CoV-2 variants including Omicron.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel and highly pathogenic coronavirus that caused an outbreak in Wuhan City, China, in 2019 and then spread rapidly throughout the world. Although several coronavirus disease 2019 (COVID-19) vaccines are currently available for mass immunization, they are less effective against emerging SARS-CoV-2 variants, especially the Omicron (B.1.1.529). Recently, we successfully produced receptor-binding domain (RBD) variants of the spike (S) protein of SARS-CoV-2 and an antigen cocktail in Nicotiana benthamiana, which are highly produced in plants and elicited high-titer antibodies with potent neutralizing activity against SARS-CoV-2. In this study, based on neutralization ability, we demonstrate that plant-produced RBD and cocktail-based vaccine candidates are highly effective against SARS-CoV-2, independently of its emerging variants. These data demonstrate that plant-produced RBD and cocktail-based proteins are the most promising vaccine candidates and may protect against Delta and Omicron-mediated COVID-19. This is the first report describing vaccines against SARS-CoV-2, which demonstrate significant activities against Delta and Omicron variants.

Protective neutralizing antibody titers reduce in time after COVID-19 vaccinations, as in individuals who have had COVID-19. This study aimed to evaluate the safety and immunogenicity of CoronaVac and TURKOVAC vaccines used as a booster dose after CoronaVac primary vaccination. This double-blind, randomized, controlled, phase II, multicenter study included healthy male and female adults (18–60 years) who were vaccinated with two doses of CoronaVac vaccine and did not exceed the duration of at least 90 days and a maximum of 270 days from the second dose of vaccination. Among 236 eligible volunteers, 222 were recruited for randomization between July 12, 2021 and September 10, 2021; 108 and 114 were randomized to the TURKOVAC and CoronaVac arms, respectively. The primary endpoint was adverse events (AEs) (ClinicalTrials.gov; Identifier: NCT04979949). On day 28, at the neutralizing antibody threshold of 1/6, the positivity rate reached 100% from 46.2% to 98.2% from 52.6% in the TURKOVAC and CoronaVac arms, respectively, against the Wuhan variant and the positivity rate reached 80.6% from 8.7% in the TURKOVAC arm vs. 71.9% from 14.0% in the CoronaVac arm against the Delta variant. IgG spike antibody positivity rate increased from 57.3% to 98.1% and from 57.9% to 97.4% in the TURKOVAC and CoronaVac arms, respectively. The TURKOVAC and CoronaVac arms were comparable regarding the frequency of overall AEs. Both vaccines administered as booster yielded higher antibody titers with acceptable safety profiles.

Crimean–Congo hemorrhagic fever virus (CCHFV), a member of the Nairoviridae family and Bunyavirales order, is transmitted to humans via tick bites or contact with the blood of infected animals. It can cause severe symptoms, including hemorrhagic fever, with a mortality rate between 5 to 30%. CCHFV is classified as a high-priority pathogen by the World Health Organization (WHO) due to its high fatality rate and the absence of effective medical countermeasures. CCHFV is endemic in several regions across the world, including Africa, Europe, the Middle East, and Asia, and has the potential for global spread. The emergence of the disease in new areas, as well as the presence of the tick vector in countries without reported cases, emphasizes the need for preventive measures to be taken. In the past, the lack of a suitable animal model susceptible to CCHFV infection has been a major obstacle in the development of vaccines and treatments. However, recent advances in biotechnology and the availability of suitable animal models have significantly expedited the development of vaccines against CCHF. These advancements have not only contributed to an enhanced understanding of the pathogenesis of CCHF but have also facilitated the evaluation of potential vaccine candidates. This review outlines the immune response to CCHFV and animal models utilized for the study of CCHFV and highlights the progress made in CCHFV vaccine studies. Despite remarkable advancements in vaccine development for CCHFV, it remains crucial to prioritize continued research, collaboration, and investment in this field.

The immunogenicity of vaccines decreases over time, causing a need for booster doses. This study aimed to present the long-term (Day 84) immunogenicity results of the double-blind, randomized, controlled, phase II Hybrid COV-RAPEL TR Study (NCT04979949), in which the TURKOVAC or CoronaVac vaccines were used as a booster after the second dose of primary vaccination with CoronaVac. A total of 190 participants from the Hybrid COV-RAPEL TR Study, who had both Day 28 and Day 84 immunogenicity results, were included. The immunogenicity on Day 84, regarding the neutralizing antibody positivity (Wuhan and Delta variants) and anti-spike immunoglobulin (Ig) G (IgG) antibody positivity, was compared between TURKOVAC and CoronaVac vaccine arms according to sex and age groups. Overall, antibody positivity showed a slight decrease on Day 84 vs. Day 28, but was not different between TURKOVAC and CoronaVac arms either for sexes or for age groups. However, TURKOVAC produced better antibody response against the Delta variant than CoronaVac, while CoronaVac was superior over TURKOVAC regarding neutralizing antibody positivity in the 50–60 years age group, regardless of the variant. A single booster dose, after the completion of the primary vaccination, increases antibody positivity on Day 28 which persists until Day 84 with a slight decrease. However, an additional booster dose may be required thereafter, since the decrease in antibody titer may be faster over time.

Crimean–Congo hemorrhagic fever (CCHF) is an emerging zoonotic infectious disease caused by Crimean–Congo hemorrhagic fever virus (CCHFV). The first clinical CCHF infection was described in 1944 in the Crimean Peninsula, exclusively in humans, with case-fatality rates exceeding 30%. The increasing number of cases, high mortality rate, and lack of effective therapy make CCHF a serious threat to public health and a potential bioterrorism agent. The present study evaluated the development, immunogenicity, and immune response durations for cell-culture-derived inactivated vaccine (CCVax) formulations in comparison with those of mouse-brain-derived vaccine (MBVax) formulations. In this study, the Kelkit06 CCHF virus strain was propagated in both suckling mice and Vero E6 cells, and purified with a sucrose gradient. Formalin-inactivated vaccine candidates were formulated at various doses [low dose (LD), 5 μg; medium dose (MD), 10 μg; high dose (HD), 20 μg)] and mixed with an alum adjuvant. BALB/c mice received the same doses of the vaccine formulations three times at 3-week intervals. The humoral endpoint IgG responses were evaluated and compared for the MBVax and CCVax treatments. The duration of the presence of IgG and neutralizing antibody (Ab) titers was evaluated and compared until up to 1 year after immunization. The humoral IgG responses indicated that the CCVax and MBVax candidates enhanced the IgG endpoint titers in a dose-dependent manner, which were induced more strongly in all the CCVax groups than in the MBVax mice. The fold changes in neutralizing Ab levels were also found to be higher in the CCVax groups: between 2- and 7.6-fold after the second week of the last immunization. The neutralization titers peaked 4 months after immunization in all the vaccine-receiving groups, but these were still comparable at the end of the first year. The CCVax formulations induced higher IgG and neutralizing Ab titers at all the measured time points. In this study, we showed that cell-culture-purified and formalin-inactivated vaccine candidates induced strong and robust immunity in vaccinated mice dose-dependently, more so than mouse-brain-derived vaccines.

We present the interim results of the efficacy, immunogenicity, and safety of the two-dose schedules of TURKOVAC versus CoronaVac. This was a randomized, observer-blinded, non-inferiority trial (NCT04942405). Volunteers were 18–55 years old and randomized at a 1:1 ratio to receive either TURKOVAC or CoronaVac at Day 0 and Day 28, both of which are 3 μg/0.5 mL of inactivated severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) adsorbed to aluminum hydroxide. The primary efficacy outcome was the prevention of polymerase chain reaction (PCR)-confirmed symptomatic coronavirus disease 2019 (COVID-19) at least 14 days after the second dose in the modified per-protocol (mPP) group. Safety analyses were performed in the modified intention-to-treat (mITT) group. Between 22 June 2021 and 7 January 2022, 1290 participants were randomized. The mITT group consisted of 915 participants, and the mPP group consisted of 732 participants. During a median follow-up of 90 (IQR 86–90) days, the relative risk reduction with TURKOVAC compared to CoronaVac was 41.03% (95% CI 12.95–60.06) for preventing PCR-confirmed symptomatic COVID-19. The incidences of adverse events (AEs) overall were 58.8% in TURKOVAC and 49.7% in CoronaVac arms (p = 0.006), with no fatalities or grade four AEs. TURKOVAC was non-inferior to CoronaVac in terms of efficacy and demonstrated a good safety and tolerability profile.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus in the Nairoviridae family within the Bunyavirales order of viruses. Crimean-Congo hemorrhagic fever (CCHF) is the most widespread among tick-borne human viral diseases. It is endemic in many areas of Africa, Asia, the Middle East, in the Balkans, Russia and countries of the former Soviet Union. The confirmed CCHF cases were seen in Spain in 2016 to signify expansion of the virus into new geographical areas. CCHFV causes a viral human disease characterized by sudden onset of fever, headache, abdominal pain, nausea, hypotension, hemorrhage, and hepatic dysfunction with fatality rates up to 30%. Currently, there are no spesific treatments or licensed vaccines available for CCHFV. The absence of a susceptible animal model for CCHFV infection was severely hindered work on the development of vaccines. However, several animal models of CCHFV infection have been recently developed and used to assess vaccine efficacy. In this study, we have used the transiently immune-suppressed (IS) mouse model that MAb-5A3 was used to block IFN-I signaling in immune intact, wild-type mice at the time of CCHFV infection to evaluate the immune response and efficacy of the cell culture based and the mouse brain derived inactivated vaccines against CCHFV. Both vaccine preparations have provided complete protection but the cell culture based vaccine more effectively induced to CCFHV spesific antibodies and T cell responses. This is the first comparison of the cell culture based and the mouse brain derived vaccines for assessing the protective efficacy and the immunogenicity in the IS mouse CCHFV model.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and associated with severe respiratory illness emerged in Wuhan, China, in late 2019. The virus has been able to spread promptly across all continents in the world. The current pandemic has posed a great threat to public health concern and safety. Currently, there are no specific treatments or licensed vaccines available for COVID-19. We isolated SARS-CoV-2 from the nasopharyngeal sample of a patient in Turkey with confirmed COVID-19. We determined that the Vero E6 and MA-104 cell lines are suitable for supporting SARS-CoV-2 that supports viral replication, development of cytopathic effect (CPE) and subsequent cell death. Phylogenetic analyses of the whole genome sequences showed that the hCoV-19/Turkey/ERAGEM-001/2020 strain clustered with the strains primarily from Australia, Canada, England, Iran and Kuwait and that the cases in the nearby clusters were reported to have travel history to Iran and to share the common unique nucleotide substitutions.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and associated with severe respiratory illness emerged in Wuhan, China, in late 2019. The virus has been able to spread promptly across all continents in the world. The current pandemic has posed a great threat to public health concern and safety. Currently, there are no specific treatments or licensed vaccines available for COVID-19. We isolated SARS-CoV-2 from the nasopharyngeal sample of a patient in Turkey with confirmed COVID-19. We determined that the Vero E6 and MA-104 cell lines are suitable for supporting SARS-CoV-2 that supports viral replication, development of cytopathic effect (CPE) and subsequent cell death. Phylogenetic analyses of the whole genome sequences showed that the hCoV-19/Turkey/ERAGEM-001/2020 strain clustered with the strains primarily from Australia, Canada, England, Iran and Kuwait and that the cases in the nearby clusters were reported to have travel history to Iran and to share the common unique nucleotide substitutions.

The COVID-19 pandemic, caused by SARS-CoV-2, has rapidly spread to more than 222 countries and has put global public health at high risk. The world urgently needs cost-effective and safe SARS-CoV-2 vaccines, antiviral, and therapeutic drugs to control it. In this study, we engineered the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein and produced it in the plant Nicotiana benthamiana in a glycosylated and deglycosylated form. Expression levels of both glycosylated (gRBD) and deglycosylated (dRBD) RBD were greater than 45 mg/kg fresh weight. The purification yields were 22 mg of pure protein/kg of plant biomass for gRBD and 20 mg for dRBD, which would be sufficient for commercialization of these vaccine candidates. The purified plant-produced RBD protein was recognized by an S protein-specific monoclonal antibody, demonstrating specific reactivity of the antibody to the plant-produced RBD proteins. The SARS-CoV-2 RBD showed specific binding to angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 receptor. In mice, the plant-produced RBD antigens elicited high titers of antibodies with a potent virus-neutralizing activity. To our knowledge, this is the first report demonstrating that mice immunized with plant-produced deglycosylated RBD form elicited high titer of RBD-specific antibodies with potent neutralizing activity against SARS-CoV-2 infection. Thus, obtained data support that plant-produced glycosylated and in vivo deglycosylated RBD antigens, developed in this study, are promising vaccine candidates for the prevention of COVID-19.

Crimean-Congo hemorrhagic fever (CCHF) is an acute tick-borne zoonotic disease. The disease has been reported in many countries of Africa, Asia, the Middle East, and in Eurasia. During the past decade, new foci of CCHF have emerged in the Balkan Peninsula, southwest Russia, the Middle East, western China, India, Africa, and Turkey. CCHF virus produces severe hemorrhagic manifestations in humans with fatality rates up to 30%. Vaccine development efforts have been significantly hampered by a lack of animal models and therefore, no protective vaccine has been achieved. Lately, IFN α/β receptor deficient (IFNAR-/-) mice have been established as a novel small animal model of CCHF virus infection. In the present study, we found that IFNAR-/- mice highly susceptible to CCHF virus Turkey-Kelkit06 strain. Immunization with the cell culture based vaccine elicited a significant level of protection against high dose challenge (1,000 PPFU) with a homologous CCHF virus in IFNAR-/- mice.