Study of Kyasanur forest disease viremia, antibody kinetics, and virus infection in target organs of Macaca radiata

Patil, Dilip R.; Yadav, Pragya D; Shete, Anita M.; Chaubal, Gouri; Mohandas, Sreelekshmy; Sahay, Rima R.; Jain, Rajlaxmi; Mote, Chandrashekhar; Kumar, Sandeep; Kaushal, Himanshu; Kore, Pravin; Patil, Savita; Majumdar, Triparna; Fulari, Siddharam; Suryawanshi, Annasaheb; Kadam, Manoj; Pardeshi, Prachi; Lakra, Rajen; Sarkale, Prasad; Mourya, Devendra T.

doi:10.1038/s41598-020-67599-x

Cited by 13 publications

(16 citation statements)

References 26 publications

(56 reference statements)

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“…All the animals were clinically evaluated for skin/systemic disorders, haemoglobin, total leukocyte count, differential leukocyte count, platelet count, packed cell volume, biochemical parameters (AST, ALT, bilirubin, serum proteins, alkaline phosphatase, LDH, BUN, creatinine, cholesterol, triglycerides, sodium, potassium and glucose), abdominal ultrasonography, chest X-ray and tuberculin test and were found fit for the study. Animals were screened for Kyasanur forest disease virus and SARS-CoV-2 and IgG antibodies were found to be negative 29,30 . Biomedic data systems temperature transponder was implanted in the interscapular region subcutaneously for monitoring of body temperature during the study.…”

Section: Methodsmentioning

confidence: 99%

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Immunogenicity and protective efficacy of inactivated SARS-CoV-2 vaccine candidate, BBV152 in rhesus macaques

et al. 2021

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The COVID-19 pandemic is a global health crisis that poses a great challenge to the public health system of affected countries. Safe and effective vaccines are needed to overcome this crisis. Here, we develop and assess the protective efficacy and immunogenicity of an inactivated SARS-CoV-2 vaccine in rhesus macaques. Twenty macaques were divided into four groups of five animals each. One group was administered a placebo, while three groups were immunized with three different vaccine candidates of BBV152 at 0 and 14 days. All the macaques were challenged with SARS-CoV-2 fourteen days after the second dose. The protective response was observed with increasing SARS-CoV-2 specific IgG and neutralizing antibody titers from 3rd-week post-immunization. Viral clearance was observed from bronchoalveolar lavage fluid, nasal swab, throat swab and lung tissues at 7 days post-infection in the vaccinated groups. No evidence of pneumonia was observed by histopathological examination in vaccinated groups, unlike the placebo group which exhibited interstitial pneumonia and localization of viral antigen in the alveolar epithelium and macrophages by immunohistochemistry. This vaccine candidate BBV152 has completed Phase I/II (NCT04471519) clinical trials in India and is presently in phase III, data of this study substantiates the immunogenicity and protective efficacy of the vaccine candidates.

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Section: Methodsmentioning

confidence: 99%

“…Anti-SARS-CoV-2 immunoreactivity in the lung tissues was assessed using mouse polyclonal serum. For IHC, mouse polyclonal serum was used as the primary antibody (1:500) and anti-mouse HRP antibody was used as secondary antibody 29,36 .…”

Section: Methodsmentioning

confidence: 99%

Immunogenicity and protective efficacy of inactivated SARS-CoV-2 vaccine candidate, BBV152 in rhesus macaques

et al. 2021

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“…The acute phase is characterized by dehydration, hypotension, bradycardia and diarrhea, while neurological signs such as tremors may be observed in the second phase (17,18,20,21). However, platelets were only mildly decreased over infection, and no hemorrhagic signs were reported in these animals (18,19).…”

Section: Introductionmentioning

confidence: 80%

“…Experimental infection of these two NHP species demonstrated that blackfaced langurs in particular are highly susceptible to KFDV and succumbed to infection during the viremic phase (17). Bonnet macaques infected with KFDV experience a biphasic illness with 10-100% lethality depending on the study (17)(18)(19)(20). The acute phase is characterized by dehydration, hypotension, bradycardia and diarrhea, while neurological signs such as tremors may be observed in the second phase (17,18,20,21).…”

Section: Introductionmentioning

confidence: 99%

A pigtailed macaque model for Kyasanur Forest disease virus and Alkhurma hemorrhagic disease virus

Feldmann

McNally

et al. 2021

Preprint

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Kyasanur Forest disease virus (KFDV) and the closely related Alkhurma hemorrhagic disease virus (AHFV) are emerging flaviviruses that cause severe viral hemorrhagic fevers in humans. Increasing geographical expansion and case numbers, particularly of KFDV in southwest India, class these viruses as a public health threat. Viral pathogenesis is not well understood and additional vaccines and antivirals are needed to effectively counter the impact of these viruses. However, current animal models for KFDV do not accurately reproduce viral tissue tropism or clinical outcomes observed in humans. Here, we show pigtailed macaques (Macaca nemestrina) infected with KFDV or AHFV develop viremia that peaks 2 to 4 days following inoculation. Over the course of infection, animals developed lymphocytopenia, thrombocytopenia, and elevated liver enzymes. Infected animals exhibited hallmark signs of human disease characterized by a flushed appearance, piloerection, dehydration, loss of appetite, weakness, and hemorrhagic signs such as epistaxis. Virus was commonly present in the gastrointestinal tract, consistent with human disease caused by KFDV and AHFV where gastrointestinal symptoms (hemorrhage, vomiting, diarrhea) are common. This work characterizes a nonhuman primate model for KFDV and AHFV that closely resembles human disease for further utilization in understanding host immunity and development of antiviral countermeasures.Author SummaryKyasanur Forest disease virus (KFDV) and Alkhurma hemorrhagic disease virus (AHFV) are tick-borne flaviviruses that cause viral hemorrhagic fevers in India and the Arabian Peninsula, respectively. Bonnet macaques and black-faced langurs are susceptible to KFDV infection, but these animals do not experience hemorrhagic signs as seen in human cases with KFDV. This work characterizes for the first time experimental infection of KFDV and AHFV in pigtailed macaques (PTMs). Infected PTMs can develop moderate to severe disease that mirrors many aspects of human disease, including some hemorrhagic signs. Together these data describe the PTM model for KFDV and AHFV as a valuable tool for future work to study viral pathogenesis and for assessing the efficacy of vaccines and antivirals.

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“…Gross examination of lungs was done to assess the degree and extent of consolidation and congestion as per the recommendation of the Working Group of the Society of Toxicologic Pathology’s Scientific and Regulatory Policy Committee (38). Histopathological examination of various lung lobes was carried out to assess the extent of interstial pneumonia, alveolar damage, haemorrhages, inflammatory cell infiltration, hyaline membrane formation and accumulation of eosinophilic oedematous exudate using the procedure as described earlier (39, 40). Immunohistochemistry (IHC) was performed on the lung tissue to detect the presence of SARS-CoV-2 antigen on type-II pneumocytes and alveolar macrophages using the techniques described elsewhere (data not shown here) (39).…”

Section: Methodsmentioning

confidence: 99%

Assessment of immunogenicity and protective efficacy of ZyCoV-D DNA vaccine candidates in Rhesus macaques against SARS-CoV-2 infection

Yadav

Kumar

Agarwal

et al. 2021

Preprint

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Vaccines remains the key protective measure to achieve herd immunity to control the disease burden and stop COVID-19 pandemic. We have developed and assessed the immunogenicity and protective efficacy of two formulations (1mg and 2mg) of ZyCoV-D (a plasmid DNA based vaccine candidates) administered through Needle Free Injection System (NFIS) and syringe-needle (intradermal) in rhesus macaques with three dose vaccine regimens. The vaccine candidate 2mg dose administered using Needle Free Injection System (NFIS) elicited a significant immune response with development of SARS-CoV-2 S1 spike region specific IgG and neutralizing antibody (NAb) titers during the immunization phase and significant enhancement in the levels after the virus challenge. In 2 mg NFIS group the IgG and NAb titers were maintained and showed gradual rise during the immunization period (15 weeks) and till 2 weeks after the virus challenge. It also conferred better protection to macaques evident by the viral clearance from nasal swab, throat swab and bronchoalveolar lavage fluid specimens in comparison with macaques from other immunized groups. In contrast, the animals from placebo group developed high levels of viremia and lung disease following the virus challenge. Besides this, the vaccine candidate also induced increase lymphocyte proliferation and cytokines response (IL-6, IL-5).The administration of the vaccine candidate with NFIS generated a better immunogenicity response in comparison to syringe-needle (intradermal route). The study demonstrated immunogenicity and protective efficacy of the vaccine candidate, ZyCoV-D in rhesus macaques.

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Study of Kyasanur forest disease viremia, antibody kinetics, and virus infection in target organs of Macaca radiata

Cited by 13 publications

References 26 publications

Immunogenicity and protective efficacy of inactivated SARS-CoV-2 vaccine candidate, BBV152 in rhesus macaques

Immunogenicity and protective efficacy of inactivated SARS-CoV-2 vaccine candidate, BBV152 in rhesus macaques

A pigtailed macaque model for Kyasanur Forest disease virus and Alkhurma hemorrhagic disease virus

Assessment of immunogenicity and protective efficacy of ZyCoV-D DNA vaccine candidates in Rhesus macaques against SARS-CoV-2 infection

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