Immunogenicity and reactogenicity of heterologous immunization schedules using Sputnik V, ChAdOx1-S, BBIBP-CorV, Ad5-nCoV and mRNA-1273
Heterologous vaccination regimens against COVID-19 provide a rational strategy to rapidly increase the rate of coverage in many regions of the world. In Argentina, a number of different vaccine platforms are being used, including the non-replicating adenovirus vaccines ChAdOx1-S, Ad5-nCoV, and Sputnik V; the mRNA vaccines BNT162b2 and mRNA-1273; and the inactivated SARS-CoV-2 vaccine BBIBP-CorV. Although data are available about mRNA and ChAdOx1 vaccines combination, very limited information has been reported combining these platforms with other vaccines widely used in developing countries, such as BBIBP-CorV and Sputnik V. We assessed the immunogenicity and reactogenicity of 15 vaccine combinations in a cohort of 1314 participants. The antibody response was evaluated by determining IgG antibodies anti-spike and serum neutralizing titers. We observed that a number of heterologous vaccine combinations are equivalent or superior to the homologous schemes. For all the cohorts analyzed, the highest antibody response was induced by mRNA-1273 as second dose. The results also highlight the benefit of using heterologous schedules in individuals primed with BBIBP-CorV. No serious adverse events were detected in any of the schedules analyzed. Our observations provide rational support for the use of different vaccine combinations with the aim of achieving wide vaccine coverage in the shortest possible time.
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Assessment of immunogenicity Antibodies to SARS-CoV-2 trimeric spike protein were quantified using an established two step ELISA previously described9. For end point titrations, samples were serially diluted in IgG SARS29 CoV-2 negative serum or fetal bovine serum (FBS) from 1/50 to 1/12800. The SARS-CoV-2 antibody concentration of each sample expressed in International Units/mL (UI/mL) was calculated by extrapolation of the OD 450 nm value on a calibration curve. For construction of the calibration curve, a WHO International Standard for anti-SARS-CoV-2 immunoglobulin was used. The linear range was defined 1 to be from 0.2 to 1.5 OD 450nm. Serial dilutions of the samples were performed to fit adequately in the linear range of the calibration curve. Serum neutralizing capacity was evaluated using the ancestral SARS-CoV-2 reference strain 2019 B.1 (GISAID Accession ID: EPI_ISL_499083), provided by Dr. Sandra Gallegos (InViV working group). Vero cells (ATCC) were cultured at 37°C in 5% CO2 in Dulbecco´s Modified Eagle’s high glucose medium (DMEM, Thermo Fisher Scientific) supplemented with 10% fetal bovine serum (FBS) (GIBCO). Serum samples were heat-inactivated (30 min, 56°C) and serial dilutions (1/2 to 1/8192) were incubated for 1h/37°C with SARS-CoV-2 in DMEM 2% FBS. Fifty l of the mixture was incubated with Vero cell in monolayers for 1 h/37°C (MOI = 0.01). The media was removed and replaced by DMEM 2% FBS. After 72 h of culture, cells were fixed with PFA 4% (4°C/20 min) and stained with crystal violet solution in methanol. The viral cytopathic effect on the monolayer was analyzed, and the neutralization titer was defined as the highest serum dilution that prevented any cytopathic effect.