This study is a non-randomized observation and comparison of immune response betweenbacteriologically confirmed TB patients under treatment cohort who received COVID-19vaccine (n=54) vs healthy individuals (n=54).Each participant will receive single or double doses of one of COVID-19 vaccines(Pfizer-BioNTech COVID-19 vaccine, AstraZeneca vaccine or Janssen Ad26.COV2.S COVID-19vaccine) in the deltoid muscle of the non-dominant arm. Study Duration approximately 1year. The main focus of this study is to compare the humoral and cellular immunologicalresponses of the COVID-19 vaccines between bacteriologically confirmed TB patients undertreatment vs healthy individuals.This study is funded by the Wellcome Trust. The grant reference number is 220211/A/20/Z.
In late 2020, COVID-19 pandemic was occurred globally. Like Tuberculosis (TB), severe
acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is primarily affected in
respiratory tract with increased risk of severe clinical complications especially in
particular risk population like diabetic patients and old ages. Like other viral
infections, there is evidence that both acquired humoral and cellular immunological
responses against the SARS-CoV-2 infection are key in providing protective immunity.
Although the magnitude and durability of both binding and neutralizing antibodies after
seroconversion of COVID-19 patients are highly variable at the individual patient level,
higher level of neutralizing antibodies appears to be correlated with protection against
reinfection.
As natural immunity alone after COVID-19 infection appears to be insufficient for
protection against COVID-19, since the beginning of COVID-19 pandemic, several COVID-19
vaccines developed based on different technical platforms have been introduced globally.
Up to August 2021, twenty COVID-19 vaccines has been included in WHO's Emergency Use
Listing (EUL).
As protection against COVID-19 infection among TB patients is critical to prevent severe
clinical outcomes, COVID-19 immunization program is carrying out among TB patients in the
SMRU TB centers with supply of COVID-19 vaccines from Ministry of public health,
Thailand. In Thailand, Pfizer-BioNTech COVID-19 vaccine, AstraZeneca vaccine and Janssen
Ad26.COV2.S COVID-19 vaccine are widely available in COVID-19 vaccination campaigns.
Pfizer-BioNTech COVID-19 vaccine is an mRNA vaccine and its two-dose regimen with
inter-dose interval of 21 days apart can provide effective protection against SARS-CoV-2-
infection. Mild local and systemic reactions can occur after vaccination but serious
adverse effects can be complicated rarely. It can also be provided for children over 6
months of age and reactogenicity is also less frequent.
AstraZeneca vaccine is a replication-deficient chimpanzee adenovirus-vectored vaccine
expressing full-length SARS CoV-2 spike glycoprotein gene. Efficacy, immunogenicity and
safety profiles of the vaccine are acceptable and reasonably well tolerated in healthy
young and old adults, symptomatic COVID-19 patients and people with HIV infection.
Janssen Ad26.COV2.S COVID-19 vaccine is a recombinant, replication-incompetent adenovirus
serotype 26 (Ad26) vector encoding a full-length and stabilized SARS-CoV-2 spike protein.
The vaccine needs single dose of administration intramuscularly into the deltoid muscle.
Multicenter, placebo-controlled, phase 1-2a trial has shown that single dose of the
vaccine has an efficacy of 66.9% against symptomatic COVID-19 infection, 76.7% against
severe COVID-19 disease after 14 days, and 85.4% after 28 days. The vaccine appears to be
safe like other COVID-19 vaccines because no severe allergic or anaphylactic reaction has
been recorded in clinical trials except from occurrence of a very rare syndrome of blood
clotting combined with low platelet counts in some countries. However, there has been no
sufficient data on pregnancy and people with co-morbidity especially HIV/TB patients.
As there is limited knowledge about immunogenicity of COVID-19 vaccines among TB
patients, examination of immunological responses from the COVID-19 vaccines offering in
community COVID-19 vaccination campaigns among TB patients as well as healthy population
is warranted. Protectability and immune response to the COVID-19 vaccines in TB patients
under treatment should be studied to get better understanding about immunological
responses among population with co-morbidity. Along with antibodies response,
reactogenicity, clinical and laboratory safety profiles of the COVID-19 vaccines in this
specific group will also be assessed and compared with the healthy control.
This study is a non-randomized observational study aimed to compare humoral and cellular
immunological responses of the COVID-19 vaccines between bacteriologically confirmed TB
patients under treatment cohort (n=54) vs healthy individuals (n=54) after receiving a
COVID-19 vaccine. Each participant will receive single or double doses of one of
aforementioned COVID-19 vaccines in the deltoid muscle of the non-dominant arm.
Follow-up appointments will be scheduled on 2nd dose visit and 28 days after 2nd dose in
double dose scheduled COVID-19 vaccines and 28 days and 56 days after vaccination in
single dose scheduled COVID-19 vaccine. For assessment of reactogenicity, participants
will be informed to attend follow-up appointments every day for 7 days following each
dose of vaccination.
Frequency, incidence and nature of solicited local and systemic adverse events (AEs) and
unsolicited AEs will be recorded at their follow up visits. For immunological responses,
humoral and cellular antibody level to SARS-CoV-2 virus will be assessed over time
(before 1st dose, before 2nd dose , 28 days after 2nd dose in double dose scheduled
COVID-19 vaccine or before single dose vaccination, 28 days and 56 days after vaccination
in single dose scheduled COVID-19 vaccine) and compared between TB patients and healthy
individuals. Baseline laboratory investigations such as liver function tests, renal
function tests, serum electrolytes, iron, complete blood count and C reactive protein
will be tested on Day 0 and rechecked on the same days as immunological tests to review
changes after vaccination.
Infection serological tests such as Human immunodeficiency virus (HIV), Hepatitis B
surface antigen (HBsAg), and Hepatitis C antibody (HCV Ab) tests will be performed at
screening visit with consent of potential participants. Moreover, nasopharyngeal swab for
COVID-19 PCR test will be tested before being enrolled. These tests can be repeated if
there are symptoms suggestive of these infections.
Biological: Pfizer-BioNTech COVID-19 vaccine
Pfizer-BioNTech COVID-19 vaccine, Messenger RNA (mRNA) based vaccine encoding the viral
spike glycoprotein (S) Formulation: Frozen concentrate before dilution with 0.9% sodium
chloride solution for injection Route of Administration: Intramuscular (IM) Dosing
regimen: Two doses (0.3 mL per dose) (at least 3 weeks apart)
Biological: AstraZeneca vaccine
AstraZeneca vaccine, a replication-deficient simian adenoviral vector expressing the
spike (S) protein of SARS-CoV-2 Formulation: Aqueous solution for injection Route of
Administration: Intramuscular (IM) Dosing regimen: Two doses (0.5 mL per dose) (at least
12 weeks apart)
Biological: Janssen Ad26.COV2.S COVID-19 vaccine
Janssen Ad26.COV2.S COVID-19 vaccine, recombinant, replication-incompetent adenovirus
serotype 26 (Ad26) vector encoding a full-length and stabilized SARS-CoV-2 spike protein.
Formulation: Suspension for injection Route of Administration: Intramuscular (IM) Dosing
regimen single dose (0.5 mL)
Inclusion Criteria:
- 18 years and above, newly diagnosed bacteriologically confirmed TB patients
including both drug sensitive and resistant TB, who are taking anti TB or MDR-TB
treatment in initial period during study period or clinically healthy individuals
for comparator arm.
- Willing to be followed for four weeks following second dose of Pfizer-BioNTech
COVID-19 vaccine and AstraZeneca vaccine or eight weeks following single dose of
Janssen Ad26.COV2.S COVID-19 vaccine
- Willing to be involved in the pre-enrolment screening.
- For women with child bearing potential only (aged 18-49 years), willing to continue
to use effective contraception methods through the study.
- For women with child bearing potential only (aged 18-49 years), negative pregnancy
test on the day of screening and on the day of vaccination to be eligible to receive
the vaccination.
- Able and willing to comply with all study requirements.
- Ability to understand the study instructions and provide written informed consent
Exclusion Criteria:
- History of laboratory confirmed COVID-19 for any duration before or positive
COVID-19 PCR or antigenic test at screening.
- History of HIV infection
- Participation in other COVID-19 related studies for the duration of the study.
- Participation in other vaccine trials within 90 days before and 30 days after the
study vaccination.
- Administration of any immunoglobulins or any type of COVID-19 vaccine within 90 days
before administration of the vaccine.
- History of allergic disease or reactions likely to be exacerbated by any component
of the vaccine.
- Any previous history of a serious side effect with any kind of vaccine.
- Any history of angioedema.
- Any history of anaphylaxis.
- Women with pregnancy, lactation or planning to get pregnant during the duration of
the study.
- Current diagnosis of or treatment for cancer.
- History of severe psychiatric disorders likely to affect participation in the study.
- Bleeding disorder (e.g. coagulation factor deficiency, coagulopathy or platelet
disorder), history of thrombosis or prior history of significant bleeding or
bruising following IM injections or venipuncture.
- Suspected or known current alcohol or drug dependency (except well controlled
condition).
- Presence of any condition which in the judgement of the investigator would place the
patient at undue risk or interfere with the results of the study.
- Severe and/or uncontrolled cardiovascular disease, gastrointestinal disease, liver
disease, renal disease, endocrine disorder and neurological illness (mild/moderate
well controlled comorbidities are allowed).
Shoklo Malaria Research Unit (SMRU)
Mae Ramat, Tak, Thailand
François Nosten, Professor, Principal Investigator
Shoklo Malaria Research Unit