COVID-19 is an infectious disease caused by SARS-CoV-2 virus, causing millions of deathsaround the globe since the beginning of the pandemic. COVID-19 vaccination was proven tobe effective at reducing both mortality and development of severe COVID-19 afterinfection. Vaccine-elicited protection is particularly important for immunocompromisedpatients, as they are more susceptible to infections with their defective immuneresponse, for instance, previous review had suggested that patients with malignancies andrecipients of solid organ transplants may be at increased risk of developing severeCOVID-19 disease and even death.To further complicate the scenario, there are two obstacles: firstly, immunocompromisedindividuals may have suboptimal response from vaccinations, as studies have shown thatrecipients of solid organ transplant have suboptimal or even are seronegative after thefourth dose booster vaccination . Secondly, with constant mutation of the SARS-CoV-2viruses, new variants evolve over time, leading to reduction in vaccine efficacy andbreakthrough infection in healthy individuals. Therefore, novel vaccine strategy shouldbe considered to enhance the vaccine response in these immunocompromised individuals.In this study, intradermal injection instead of intramuscular injection for vaccinedelivery is proposed, as the investigators have observed improved immunogenicity and fewadverse events from previous experience of influenza vaccination. The study aims toevaluate the immunogenicity, safety and tolerability of intradermal COVID-19 vaccinationin immunocompromised patients.
This is a randomized controlled trial performed in the Hong Kong West Cluster Hospitals
under the Hospital Authority in Hong Kong. Immunocompromised individuals who completed
two doses of COVID-19 vaccine are recruited and received a booster dose of BNT162b2
vaccine. Recruited individuals include patients who received solid organ transplant
(SOT), patients who received stem cell or bone marrow transplant (SCBOT), patients who
are undergoing chemotherapy or immunotherapy (COI) and patients who are receiving
biologics therapy (BI). The study was approved by the institutional review board of the
University of Hong Kong and Hospital Authority (UW 21-214).
After recruitment, participants are randomized to receive either one 30-μg dose (0.3 mL)
of intramuscular BNT162b2 booster dose vaccination or one 30-μg dose (0.3 mL) of
intradermal BNT162b2 booster dose vaccination. In addition, participants are further
subdivided into different groups based on the priming vaccine received. Participant's
blood samples are collected before booster vaccination (baseline), 28 days after booster
dose, 3 months after booster dose and 6 months after booster dose vaccination. Blood
samples collected are tested with live virus microneutralization assay (vMN), performed
in the Biosafety level 3 facility of HKU to determine the level of neutralizing antibody
in sera. Serial 2-fold dilutions of serum starting from 1:10 are incubated with 100
median tissue culture infectious doses (TCID50) of ancestral strain SARS-CoV-2, BA.1,
BA.5.2, and XBB for 1.5 h at 37 °C. Then, a serum-virus mixture is added to
VeroE6/TMPRSS2 cells (JCRB Cell Bank Catalogue no. JCRB1819) on 96-well plates. After 72
h of incubation at 37 °C and 5% CO2, the cytopathic effect (CPE) is examined and the
antibody titre is determined by the highest dilution with 50% inhibition of CPE. In
addition, A Surrogate SARS-CoV-2 neutralizing antibody (NAb) is performed to determine
the level of NAb in serum sample. Testing is performed using a one-step competitive
chemiluminescence immunoassay on the iFlash 1800 analyzer, as described in our previous
study.
To assess the safety and adverse events of the vaccination, participants are asked to
record any adverse events for 4 weeks after the booster dose.
The primary endpoint of this study is the vMN geometric mean titre (GMT) against WT,
BA.1, BA.5.2 and XBB. The secondary endpoints are GMT fold increase and safety. Severe
adverse events (SAEs) are defined as death, disabling or life-threatening conditions
related to vaccine; Adverse events (AE) include fever (>38 °C), chills, headache,
tiredness, nausea, vomit, diarrhea, muscle pain, joint pain, facial dropping, skin rash
or injection site reactions (pain, redness, swelling, ecchymoses, itching).
Biological: ID BNT162b2 vaccine
intradermal BNT162b2 vaccine
Biological: IM BNT162b2 vaccine
intramuscular BNT162b2 vaccine
Inclusion Criteria:
1. Recruited subjects include adult subjects ≥18 years
2. Immunocompromised subjects as defined by the following.
1. Patients who have undergone solid organ or stem cell transplantation and on
immunosuppressive medication.
2. Patients who are on chemotherapy, biologics or other immunosuppressive therapy.
3. Patients who are on high-dose corticosteroid (prednisolone 0.5mg/kg daily or
equivalent)
3. Negative IgG antibody response against Covid19 14 days after the second dose of
Covid19 vaccination.
4. All subjects have to give written informed consent.
5. Subjects must be available to complete the study and comply with study procedures.
Willingness to allow for serum samples to be stored beyond the study period, for
potential additional future testing to better characterize immune response
Exclusion Criteria:
1. Inability to comprehend and to follow all required study procedures.
2. Have a recent history (documented, confirmed or suspected) of a flu-like disease
within a week of vaccination.
3. Have a known allergy to polyethylene glycol (PEG) or other components of the study
vaccines, or history of any anaphylaxis, serious vaccine reactions, to any
excipients.
4. Have known active human immunodeficiency virus (HIV) infection.
5. Received an experimental agent (vaccine, drug, biologic, device, blood product, or
medication) within 1 month prior to vaccination in this study or expect to receive
an experimental agent during this study. Unwilling to refuse participation in
another clinical study through the end of this study.
6. Tympanic temperature ≥ 38°C within 3 days of intended study vaccination
7. Have a history of alcohol or drug abuse in the last 5 years.
8. Have any condition that the investigator believes may interfere with successful
completion of the study
Queen Mary Hospital
Hong Kong, Hong Kong
Investigator: Ivan FN Hung, MD
Contact: 22553424
ivanhung@hku.hk
Ivan FN Hung, MD
22553424
ivanhung@hku.hk
Ricky Zhang, PhD
22554049
zhangrq@hku.hk
Ivan FN Hung, MD, Principal Investigator
The University of Hong Kong