An Immunogenicity Report for the Comparison between Heterologous and Homologous Prime-Boost Schedules with ChAdOx1-S and BNT162b2 Vaccines

Abstract

Background: There is a small amount of immunological data on COVID-19 heterologous vaccination schedules in humans. We assessed the immunogenicity of BNT162b2 (Pfizer/BioNTech) administered as a second dose in healthcare workers primed with ChAdOx1-S (Vaxzevria, AstraZeneca). Methods: 197 healthcare workers were included in a monocentric observational study in Foch hospital, France, between June and July 2021. The main outcome was the immunogenicity measured by serum SARS-CoV-2 IgG antibodies. Results: 130 participants received the ChAdOx1-S/BNT vaccine and 67 received the BNT/BNT vaccine. The geometric mean of IgG antibodies was significantly higher in the BNT/BNT vaccine group compared to the ChAdOx1-S/BNT vaccine group, namely 10,734.9, 95% CI (9141.1–12,589.3) vs. 7268.6, 95% CI (6501.3–8128.3), respectively (p < 0.001). However, after adjustment for time duration between the prime and second vaccinations, no significant difference was observed (p = 0.181). A negative correlation between antibody levels and time duration between second dose and serology test was observed for the BNT/BNT vaccine (p < 0.001), which remained significant after adjustment for all covariates (p < 0.001), but not for the ChAdOx1-S/BNT vaccine (p = 0.467). Conclusions: Heterologous and homologous schedules of ChAdOx1-S and BNT vaccines present robust immune responses after the second vaccination. The results observed were equivalent after adjustment for covariates and emphasize the importance of flexibility in deploying mRNA and viral vectored vaccines. Nevertheless, applying the ChAdOx1-S schedule vaccination for the heterologous second dose of BNT was associated with decreased IgG antibody levels compared to the homologous BNT/BNT vaccination.

Booster vaccination strategy: Necessity, immunization objectives, immunization strategy, and safety

“… 49,51–55 Homologous inoculation will trigger a robust immune memory response to the same aspects of the viral immunogens presented during the primary immunizations but more quickly and with higher abundance. It will also increase the maturity of the immune response and its protective capacity 49,51–55 . When the heterologous inoculation strategy is adopted, the immune system provides some of the same components and novel components, thereby broadening the immune response and producing a more balanced and comprehensive immune response.…”

“…Homologous inoculation and heterologous inoculation provide advantages and disadvantages (Table 2). 49,51–55 Homologous inoculation will trigger a robust immune memory response to the same aspects of the viral immunogens presented during the primary immunizations but more quickly and with higher abundance. It will also increase the maturity of the immune response and its protective capacity 49,51–55 .…”

“…It will also increase the maturity of the immune response and its protective capacity. 49,[51][52][53][54][55] When the heterologous inoculation strategy is adopted, the immune system provides some of the same components and novel components, thereby broadening the immune response and producing a more balanced and comprehensive immune response. A heterologous vaccination strategy can achieve a persistent and broader response than a single vaccine.…”

A Systematic Review on COVID-19 Vaccine Strategies, Their Effectiveness, and Issues

“…Here, the heterologous vaccination of two different types of vaccines is administered as prime and booster doses, respectively. This strategy is not entirely a novel idea, as such heterologous vaccination methods have been applied previously for HIV and Ebola [255]. In the case of the SARS-CoV-2 vaccine, a few heterologous approaches have already been studied in different countries.…”

Duration of SARS-CoV-2 Immune Responses Up to Six Months Following Homologous or Heterologous Primary Immunization with ChAdOx1 nCoV-19 and BNT162b2 mRNA Vaccines

“…In the global struggle to achieve and maintain efficient COVID-19 vaccine programs, heterologous vaccine regimens attract great interest [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. With tolerable safety [ 1 , 8 , 9 ], and both immunogenicity [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 10 , 11 , 12 , 13 , 14 ] and effectiveness [ 15 , 16 , 17 , 18 , 19 , 20 ] exceeding that of homologous adenovector immunization, heterologous primary vaccination is as of 7 December 2021 recommended by European Medical Agency and European Centre for Disease prevention and Control [ 21 ]. However, more data on the duration of immune responses following heterologous primary vaccine protocols are needed [ 21 , 22 ].…”