300 adults ≥30 years of age who have previously received two doses of an inactivatedCOVID-19 vaccine at least 3 months earlier will receive a third dose with an mRNA vaccine(BNT162b2, BioNTech). Investigators will monitor reactogenicity and measure the immuneresponse to the third dose.
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.
Biological: BNT162b2
BNT162b2 mRNA vaccine (Cominarty®, BioNTech/Fosun Pharma), one dose (0.3mL after
dilution) contains 30 micrograms of COVID-19 mRNA Vaccine embedded in lipid
nanoparticles.
Other Name: Comirnaty
Inclusion Criteria:
- Aged 30 years or older at enrolment.
- Have received two doses of any inactivated COVID-19 vaccines (for example Sinovac-
CoronaVac, Sinopharm-BIBP) with the most recent dose at least 90 days prior to
enrolment.
- Currently resident and planning to remain resident in Hong Kong during the duration
of the study, i.e. for 12 months after enrolment.
- Agreement to refrain from blood donation during the course of the study.
- Willing to provide blood samples for all the required time points.
- The individual or their caregiver have a home phone or cellular or mobile phone for
communications purpose.
- Capable of providing informed consent.
Exclusion Criteria:
- A history of laboratory-confirmed or clinically confirmed COVID-19 infection. Have
received (at least one dose of) any COVID-19 vaccines other than inactivated
vaccines.
- Individuals who report any medical condition, or as determined by a clinician, not
suitable to receive mRNA vaccines, including but not limited to allergies to the
active substance or other ingredients of the vaccine.
- With diagnosed medical conditions related to their immune system.
- Use of medication that impairs immune system in the last 6 months, except topical
steroids or short-term oral steroids (course lasting ≤ 14 days).
- Have used immunoglobulins and/or any blood products within 90 days prior to
enrolment (administration of the study vaccine).
- Pregnancy, lactation or intention to become pregnant in the coming 3 months.
The University of Hong Kong
Hong Kong, Hong Kong
Benjamin J Cowling, PhD, Principal Investigator
The University of Hong Kong