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.

The COVID-19 pandemic is a global health crisis that has severely affected mankind and posed a great challenge to the public health system of affected countries. The availability of a safe and effective vaccine is the need of the hour to overcome this crisis. Here, we have developed and assessed the protective efficacy and immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152) in rhesus macaques (Macaca mulata). 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 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 showed features of interstitial pneumonia and localization of viral antigen in the alveolar epithelium and macrophages by immunohistochemistry. Data from this study substantiate the immunogenicity of the vaccine candidates and BBV152 is being evaluated in Phase I clinical trials in India (NCT04471519).

Background & objectives: Since the beginning of the year 2020, the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacted humankind adversely in almost all spheres of life. The virus belongs to the genus Betacoronavirus of the family Coronaviridae . SARS-CoV-2 causes the disease known as coronavirus disease 2019 (COVID-19) with mild-to-severe respiratory illness. The currently available diagnostic tools for the diagnosis of COVID-19 are mainly based on molecular assays. Real-time reverse transcription-polymerase chain reaction is the only diagnostic method currently recommended by the World Health Organization for COVID-19. With the rapid spread of SARS-CoV-2, it is necessary to utilize other tests, which would determine the burden of the disease as well as the spread of the outbreak. Considering the need for the development of such a screening test, an attempt was made to develop and evaluate an IgG-based ELISA for COVID-19. Methods: A total of 513 blood samples (131 positive, 382 negative for SARS-CoV-2) were collected and tested by microneutralization test (MNT). Antigen stock of SARS-CoV-2 was prepared by propagating the virus in Vero CCL-81 cells. An IgG capture ELISA was developed for serological detection of anti-SARS-CoV-2 IgG in serum samples. The end point cut-off values were determined by using receiver operating characteristic (ROC) curve. Inter-assay variability was determined. Results: The developed ELISA was found to be 92.37 per cent sensitive, 97.9 per cent specific, robust and reproducible. The positive and negative predictive values were 94.44 and 98.14 per cent, respectively. Interpretation & conclusions: This indigenously developed IgG ELISA was found to be sensitive and specific for the detection of anti-SARS-CoV-2 IgG in human serum samples. This assay may be used for determining seroprevalence of SARS-CoV-2 in a population exposed to the virus.

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Japanese encephalitis virus (JEV) is one of the leading causes of epidemic encephalitis in South Asian countries. Due to the short-term viremia, detecting IgM antibodies by ELISA is treated as the front-line diagnostic assay. Co-circulation and multiple exposures to antigenically cross-reactive flaviviruses in India pose a challenge in serodiagnosis. Replacing the whole virus antigen currently used in the JE IgM detection kits (ELISA) may improve the specificity and sensitivity of the existing JE MAC ELISA kits. For this purpose, we developed a stably transfected cell clone, BHK-IE6, which expresses a high amount of VLPs up to 37 µg/ml and is consistent in expression up to 40 passages. For the expression of VLPs in the secretory form, we cloned the JEV G-I prM-E coding gene along with the C-terminal signal sequence of capsid protein in the BHK-21 cells using the pcDNA3.1 + mammalian expression vector. The immune assays performed demonstrated its immune reactivity equivalent to the parental JEV strain. Simultaneously performed ELISAs using the whole virus antigen and newly developed antigen gave comparable results for JE positive and negative samples, which established the utility of developed JEV E-VLP as an antigen. Reduced cross-reactivity and increased specificity were observed when tested with dual positive sera for anti-JEV and DENV antibodies. These findings confirm the efficiency and reliability of newly developed recombinant E-VLP antigen expressed by the BHK-IE6 cell clone as an antigen in serodiagnostic assays. The implementation and progress in developing cross-reactivity-reduced antigens would improve serodiagnosis and disease burden estimates of flavivirus infection. Key points • pcDNA3.1/JE-Sig-prM-E plasmid transfected BHK-21 cells stably express VLPs. • Sodium butyrate induction enhanced the extracellular expression of VLPs.• Application of JEV-E VLPs increases the specificity of JE IgM ELISA.