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. 2022 Aug 16;3(8):100706.
doi: 10.1016/j.xcrm.2022.100706. Epub 2022 Aug 3.

Immunogenicity and reactogenicity of heterologous immunization against SARS CoV-2 using Sputnik V, ChAdOx1-S, BBIBP-CorV, Ad5-nCoV, and mRNA-1273

Carla A Pascuale  1 , Augusto Varese  2 , Diego S Ojeda  1 , Marina E Pasinovich  3 , Laura Lopez  4 , Andres H Rossi  1 , Pamela E Rodriguez  1 , Esteban A Miglietta  1 ; Laboratorio SeVa Group  1 ; Ignacio Mazzitelli  2 , Facundo Di Diego Garcia  2 , Lautaro Sanchez  1 , Santiago Oviedo Rouco  1 , María Mora Gonzalez Lopez Ledesma  1 , Juan Pablo Zurano  5 , Bianca Mazzitelli  2 , Graciela Scruzzi  4 , Paula Barbero  4 , Diego Cardozo  4 , Sandra Gallego  6 , Mariel Borda  4 , Miguel Diaz  4 ; Ministerio de Salud de la Provincia de Córdoba Group  4 ; UNC-Fac. Cs. Médicas-InViV Group  6 ; Francisco Ridao  7 , Angela Brigido Rosales  7 ; Ministerio de Salud de la Provincia de La Rioja Group  7 ; Jorge Bhon  8 , Juan M Talia  8 , María E Diangelo  9 , María A Lacaze  8 ; Ministerio de Salud de la Provincia de San Luis Group  8 ; Balanzino Aime  10 , Sebastian Isaac Gutierrez  10 , Regina Ercole  11 , Rosana Toro  12 , Lorena Tau  13 , Laura Delaplace  13 , Malena Ferreyra Compagnucci  13 ; Universidad Nacional de La Plata Group  13 ; Celeste Sartori  14 , Isabel Desimone  15 , Cecilia Echegoyen  16 , Pilar Velazquez  17 , Clarisa Testa  17 ; Ministerio de Salud de la Provincia de Buenos Aires Group  17 ; Daniela Hozbor  18 , Guillermo Docena  13 , Carlos H Laino  7 , Nicolas Kreplak  17 , Marina Pifano  17 , Gabriela Barbas  4 , Analía Rearte  3 , Carla Vizzotti  3 , Juan M Castelli  19 , Jorge Geffner  20 , Andrea V Gamarnik  21
Affiliations

Immunogenicity and reactogenicity of heterologous immunization against SARS CoV-2 using Sputnik V, ChAdOx1-S, BBIBP-CorV, Ad5-nCoV, and mRNA-1273

Carla A Pascuale et al. Cell Rep Med. .

Abstract

Heterologous vaccination against coronavirus disease 2019 (COVID-19) provides a rational strategy to rapidly increase vaccination coverage in many regions of the world. Although data regarding messenger RNA (mRNA) and ChAdOx1 vaccine combinations are available, there is limited information about the combination of these platforms with other vaccines widely used in developing countries, such as BBIBP-CorV and Sputnik V. Here, we assess the immunogenicity and reactogenicity of 15 vaccine combinations in 1,314 participants. We evaluate immunoglobulin G (IgG) anti-spike response and virus neutralizing titers and observe that a number of heterologous vaccine combinations are equivalent or superior to homologous schemes. For all cohorts in this study, the highest antibody response is induced by mRNA-1273 as the second dose. No serious adverse events are detected in any of the schedules analyzed. Our observations provide rational support for the use of different vaccine combinations to achieve wide vaccine coverage in the shortest possible time.

Keywords: Ad5-nCoV; BBIBP-CorV; ChAdOx1-S; Omicron variant; SARS-CoV-2; Sputnik V; heterologous vaccination; humoral response; mRNA-1273; neutralizing antibodies.

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Conflict of interest statement

Declaration of interests All authors declare no competing interests. This study has received funding from the Russian Direct Investment Fund, which manufactures and markets the vaccine Sputnik V, developed by the Gamaleya Research Center of Epidemiology and Microbiology.

Figures

None
Graphical abstract
Figure 1
Figure 1
Cohort description For each scheme, the number of participants, the median time, and the range between doses are indicated.
Figure 2
Figure 2
Adverse events of solicited local and systemic reactions in days 0–7 following the application of the second vaccine dose by study arm via telephone contacting Adverse events included either local reactions (A) (pain, erythema, and swelling) or systemic reactions (B) (headache, fever, and diarrhea). The proportion of participants with local or systemic adverse event was reported by vaccine schedule, and statistical analysis was performed using the χ2 test. Statistical significance is shown with the following notations: ∗p < 0.05, ns, not significant. Sputnik V C1 vaccine (rAd26, Gamaleya), Sputnik V C2 vaccine (rAd5, Gamaleya), ChAdOx1-S vaccine (AstraZeneca), BBIBP-CorV vaccine (Sinopharm), Ad5-nCoV vaccine (CanSino), mRNA-1273 vaccine (Moderna).
Figure 3
Figure 3
Antibody response in participants with homologous and heterologous vaccine combinations evaluated at day 14 after second dose administration (A) IgG anti-spike antibody levels quantified according to the WHO International Antibody Standard. The geometric means with 95% confidence intervals are shown. As reference, the level of IgG anti-spike antibodies for convalescents and a group that was vaccinated with a two-dose scheme of mRNA-1273 are shown on the right. (B) Neutralizing titers of serum antibodies against the ancestral SARS-CoV-2 B1 variant of samples shown in (A). The geometric means with 95% confidence intervals are shown. Mann-Whitney test was used to compare the two-dose mRNA-1273 vaccine reference with the heterologous arms including Sputnik V C1, ChAdOx1-S, and BBIBP-CorV as first dose and the mRNA-1273 vaccine as second dose. (C) Non-inferiority analysis for the antibody response of heterologous schedules compared with homologous schedules at day 14 after the administration of the second dose. The heterologous group was considered inferior or superior to the homologous group if the lower limit of the one-sided 97.5% confidence interval (CI) was lower than 0.63 or greater than 1, respectively. Geometric mean ratio (GMR) and two-sided 95% CIs are presented. Sputnik V C1 vaccine (rAd26, Gamaleya), Sputnik V C2 vaccine (rAd5, Gamaleya), ChAdOx1-S vaccine (AstraZeneca), BBIBP-CorV vaccine (Sinopharm), Ad5-nCoV vaccine (CanSino), mRNA-1273 vaccine (Moderna). See also Figures S1–S3.
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