Randomized comparison of 3rd dose with inactivated vaccine (CoronaVac) or mRNA vaccine(Comirnaty) in adults who previously received two doses of CoronaVac (Sinovac) or twodoses of BNT162b2 (Comirnaty, BioNTech/Fosun Pharma) at least 6 months earlier.
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 comparing the advantages of alternative booster
doses in individuals who have previously received two doses of an inactivated COVID-19
vaccine or two doses of an mRNA vaccine.
Aims and primary objectives: The aims of this study are: (1) to compare the SARS-CoV-2
antibody responses to one dose of BNT162b2 (mRNA vaccine, Fosun/BioNTech) versus one dose
of CoronaVac (inactivated vaccine, Sinovac) in individuals who have previously received
two doses of COVID-19 vaccination using BNT162b2 (mRNA vaccine, Fosun/BioNTech) or
CoronaVac (inactivated vaccine, Sinovac), and (2) to assess the reactogenicity and safety
of one booster dose of BNT162b2 and CoronaVac. The specific primary objective of our
study is to assess the vaccine (humoral) immunogenicity, proxied by SARS-CoV-2 serum
neutralizing antibody titers, of one booster dose of BNT162b2 or CoronaVac at 28 days
after the booster dose in individuals who have previously received two doses of a
COVID-19 vaccine.
Study design: Randomized open label trial in adults aged 18 years of age or older (at
enrolment). The duration of participation for each participant will be 12 months from the
administration of the vaccination booster dose. The immune response and reactogenicity of
one dose of BNT162b2 or CoronaVac will be investigated in individuals who previously
received two doses of COVID-19 vaccine at least 6 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. A subset of 25% of participants will provide additional blood samples at day
0, 7 and 30 for assessment of cellular immune responses.
Main outcomes: The primary outcome is the vaccine (humoral) immunogenicity measured as
SARS- CoV-2 serum neutralizing antibodies, evaluated as the geometric mean titer (GMT) at
28 days after the booster doses. 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); (2) a comparison of
cellular immune responses at day 7 and 30 compared to day 0; (3) descriptive analysis of
the reactogenicity and safety profiles of the booster doses.
Target population: Adults aged 18 years or older
Number of subjects planned: 400 participants to be recruited in 2021-22
Study Duration: 12 months, from September 2021 through to March 2023
Potential implications: This study will provide important evidence into the comparative
effects of using a dose of mRNA vaccine or inactivated vaccine to boost the immune
response in individuals that had previously received two doses of COVID-19 vaccination.
This information together with data collected on reactogenicity and safety could inform
COVID-19 vaccination policy locally and internationally.
Biological: BNT162b2
BNT162b2 is a nucleoside-modified mRNA encoding the trimerized SARS-CoV-2 spike
glycoprotein. The vaccine is formulated in lipid nanoparticles that increase the
efficiency of delivery of the mRNA into cells after intramuscular injection. BNT162b2
encodes the SARS- CoV-2 full-length spike, modified by two proline mutations to lock it
in the prefusion conformation and more closely recreate the intact virus with which the
elicited virus- neutralizing antibodies interact. mRNA vaccines use the pathogen's
genetic code as the vaccine; hence they exploit the host cells to translate the code and
generate the target spike protein. The protein then acts as an intracellular antigen to
stimulate the immune response of the vaccinated individual. The mRNA is then degraded
within days.
Other Name: Comirnaty
Biological: CoronaVac
CoronaVac is a Vero cell-based, aluminium hydroxide-adjuvanted, β-propiolactone-
inactivated vaccine based on the CZ02 strain. This strain of SARS-CoV-2 was isolated from
the bronchoalveolar lavage of a hospitalized patient and is closely related to the
2019-nCoV- BetaCoV Wuhan/WIV04/2019 strain. Each 0.5 ml dose is composed of 3 μg of
inactivated SARS-CoV-2 virus. The excipients are aluminium hydroxide, disodium hydrogen
phosphate, sodium dihydrogen phosphate, sodium chloride, and water for injection.
Inclusion Criteria:
- Aged 18 years or older at enrolment.
- Have received two doses of BNT162b2 OR two doses of CoronaVac, with the most recent
dose at least six months 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 prior
to enrolment.
- Have previously already received one or two doses of any COVID-19 vaccines except
CoronaVac or BNT162b2, for example but not limited to BBIBP-CorV (inactivated
vaccine, Sinopharm), AZD1222 (adenovirus vector-based vaccine, Oxford/AstraZeneca),
Sputnik V (adenovirus vector-based vaccine, Gamaleya Research Institute) and
Ad26.COV2.S (adenovirus vector-based vaccine, Johnson & Johnson).
- Individuals who report any medical condition, or as determined by a clinician, not
suitable to receive mRNA or inactivated COVID-19 vaccines, including but not limited
to allergies to the active substance or other ingredients of the vaccine.
- Currently 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).
- Administration of immunoglobulins and/or any blood products within 90 days preceding
the planned administration of the study vaccines.
- 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