A combination of potently neutralizing monoclonal antibodies isolated from an Indian convalescent donor protects against the SARS-CoV-2 Delta variant.

Although efficacious vaccines have significantly reduced the morbidity and mortality of COVID-19, there remains an unmet medical need for treatment options, which monoclonal antibodies (mAbs) can potentially fill. This unmet need is exacerbated by the emergence and spread of SARS-CoV-2 variants of concern (VOCs) that have shown some resistance to vaccine responses. Here we report the isolation of five neutralizing mAbs from an Indian convalescent donor, out of which two (THSC20.HVTR04 and THSC20.HVTR26) showed potent neutralization of SARS-CoV-2 VOCs at picomolar concentrations, including the Delta variant (B.1.617.2). One of these (THSC20.HVTR26) also retained activity against the Omicron variant. These two mAbs target non-overlapping epitopes on the receptor-binding domain (RBD) of the spike protein and prevent virus attachment to its host receptor, human angiotensin converting enzyme-2 (hACE2). Furthermore, the mAb cocktail demonstrated protection against the Delta variant at low antibody doses when passively administered in the K18 hACE2 transgenic mice model, highlighting their potential as a cocktail for prophylactic and therapeutic applications. Developing the capacity to rapidly discover and develop mAbs effective against highly transmissible pathogens like coronaviruses at a local level, especially in a low- and middle-income country (LMIC) such as India, will enable prompt responses to future pandemics as an important component of global pandemic preparedness.

Development and Utilization of VHH Antibodies Derived from Camelus Dromedarius Against Foot-and-Mouth Disease Virus.

Foot-and-mouth disease (FMD) is an acute, highly contagious, and economically devastating viral disease of domestic and wildlife species. For effective implementation of FMD control program, there is an imperative need for developing a rapid, sensitive, and specific diagnostics which help in the identification of serotypes involved in the outbreaks. The humoral immune response of the Camelidae is unique since in these animals 75% of circulating antibodies are constituted by heavy-chain antibodies and 25% are conventional immunoglobulin with two identical heavy chains. In the present study, we developed and characterized FMD virus-specific single-domain heavy-chain antibodies (VHHs) against inactivated whole-virus antigens of FMDV serotypes O (INDR2/1975), A (IND40/2000), and Asia 1 (IND63/1972) vaccine strains. After six rounds of panning and enrichment, these VHHs were stably expressed in Escherichia coli cells. The VHHs directed against outer capsid proteins of FMD virus were successfully utilized as the capture antibody in liquid-phase blocking ELISA (LPBE) thus replacing rabbit coating antibodies. Our study demonstrated the utility of FMD virus-specific VHHs as potential candidates in FMD research and diagnostic application.

Sub-optimal neutralisation of omicron (B.1.1.529) variant by antibodies induced by vaccine alone or SARS-CoV-2 Infection plus vaccine (hybrid immunity) post 6-months.

BACKGROUND: Rapid spread of the omicron SARS-CoV-2 variant despite extensive vaccination suggests immune escape. The neutralising ability of different vaccines alone or with natural SARS-CoV-2 infection against omicron is not well-known. METHODS: In this cross-sectional study, we tested the ability of vaccine and natural infection induced antibodies to neutralise omicron variant in a live virus neutralisation assay in four groups of individuals: (i) ChAdOx1 nCoV-19 vaccination, (ii) ChAdOx1 nCoV-19 vaccination plus prior SARS-CoV-2 infection, (iii) vaccination with inactivated virus vaccine (BBV152), and (iv) BBV152 vaccination plus prior SARS-CoV-2 infection. Primary outcome was fold-change in virus neutralisation titre against omicron compared with ancestral virus. FINDINGS: We included 80 subjects. The geometric mean titre (GMT) of the 50% focus reduction neutralisation test (FRNT50) was 380·4 (95% CI: 221·1, 654·7) against the ancestral virus with BBV152 vaccination and 379·3 (95% CI: 185·6, 775·2) with ChAdOx1 nCov-19 vaccination alone. GMT for vaccination plus infection groups were 806·1 (95% CI: 478·5, 1357·8) and 1526·2 (95% CI: 853·2, 2730·0), respectively. Against omicron variant, only 5 out of 20 in both BBV152 and ChAdOx1 nCoV-19 vaccine only groups, 6 out of 20 in BBV152 plus prior SARS-CoV-2 infection group, and 9 out of 20 in ChAdOx1 nCoV-19 plus prior SARS-CoV-2 infection group exhibited neutralisation titres above the lower limit of quantification (1:20) suggesting better neutralisation with prior infection. A reduction of 26·6 and 25·7 fold in FRNT50 titres against Omicron compared to ancestral SARS-CoV-2 strain was observed for individuals without prior SARS-CoV-2 infection vaccinated with BBV152 and ChAdOx1 nCoV-19, respectively. The corresponding reduction was 57·1 and 58·1 fold, respectively, for vaccinated individuals with prior infection. The 50% neutralisation titre against omicron demonstrated moderate correlation with serum anti-RBD IgG levels [Spearman r: 0·58 (0·41, 0·71)]. INTERPRETATION: Significant reduction in the neutralising ability of both vaccine-induced and vaccine plus infection-induced antibodies was observed for omicron variant which might explain immune escape. FUNDING: Department of Biotechnology, India; Bill & Melinda Gates Foundation, USA.