Background: The accrual of population immunity to COVID-19 could allow life to return to pre- pandemic normality. Immunity can be acquired through natural infections or, preferably, by vaccination. An unprecedented global effort has succeeded in developing a number of COVID-19 vaccines. All vaccines against COVID-19 approved until now have originally been developed as either a single dose or following a homologous two-dose regimen. Inactivated COVID-19 vaccines have shown inferior immunogenicity compared to mRNA vaccines but there are no studies looking into the immunogenicity, reactogenicity and safety profile of mRNA vaccination provided as a booster dose in individuals who have previously received two doses of an inactivated COVID-19 vaccine.
Aims and Objectives: The aims of this study are: (1) to determine whether one dose of mRNA vaccine can boost neutralizing antibodies against SARS-CoV-2 in individuals who have previously received two doses of inactivated COVID-19 vaccines, and (2) to assess the reactogenicity and safety of heterologous 3rd doses of vaccination. The specific primary objective of this study is to assess the vaccine (humoral) immunogenicity, proxy by SARS-CoV-2 serum neutralizing antibody titers, of a 3rd dose dose of mRNA vaccine (using BNT162b2, Fosun/BioNTech) at 28 days after the booster dose in individuals who have previously received two doses of any inactivated COVID-19 vaccines.
Study design: Open label trial in adults aged 30 years of age or older (at enrolment). The duration of participation for each participant will be 12 months from the administration of the 3rd vaccine dose. The immune response and reactogenicity of one dose of BNT162b2 will be investigated in individuals who previously received two doses of any inactivated COVID-19 vaccines at least 3 months earlier. Participants will be enrolled shortly before receiving the booster dose of BNT162b2 (day 0), with blood collection at days 0, 28, 182 and 365 days after enrolment for analysis of humoral immune responses.
Main outcomes: The primary outcome is the vaccine immunogenicity measured as SARS-CoV-2 serum neutralizing antibodies in individuals who previously received two doses of any inactivated COVID-19 vaccines, evaluated as the geometric mean titer (GMT) at 28 days after the 3rd dose. The secondary outcomes include (1) a comparison of SARS- CoV-2 serum neutralizing antibodies as the geometric mean fold rise from baseline to each post-vaccination timepoint (i.e. at days 28, 182 and 365), and (2) descriptive analysis of the reactogenicity and safety profile of the 3rd dose.
Target population: Adults aged 30 years or older
Number of Subjects Planned: 300 participants to be recruited between September 2021 and December 2021
Study duration: 12 months for each participant
Potential implications: This study will provide important evidence into the effects of using a 3rd dose of mRNA vaccines to boost the immune response in individuals that had previously received two doses of inactivated vaccines. This information together with data collected on reactogenicity and safety could inform COVID-19 vaccination policy locally and internationally.
