SARS-CoV-2 is a highly transmissible and pathogenic coronavirus that emerged in late 2019and has caused a pandemic of acute respiratory disease, collectively known as COVID-19.Given the relatively short duration of protection after vaccination or SARS-CoV-2infection and the evolution of immune-evading strains, it is likely that the populationwill have to be repeatedly boosted until a "universal" Pan-Sarbecovirus vaccine isavailable.SARS-CoV-2 protein subunit vaccine candidates have shown that, despite adjuvantation,their safety/reactogenicity profile seems to be preferable over mRNA or vectoredvaccines, whilst inducing non-inferior immune responses (1,2).In this regard, serious adverse events of special interest from mRNA vaccines seem to behave been substantially underestimated/underreported. In a preliminary analysis by anInternational consortium, the true incidence seems to be 1,250/million excess risk invaccinees instead of the 1-2/million reported by the Department of Health and HumanServices (3,4). Additionally, in a recent study, the Clover SCB-2019 protein subunitvaccine candidate has shown higher neutralizing antibodies titers against the omicronvariant, when compared to an inactivated vaccine (data not published yet). AlthoughBrazil has various vaccine platforms authorized for emergency use or licensed, such asmRNA vaccines, vector-based vaccines, inactivated vaccines, so far Brazil has no accessto adjuvanted or non-adjuvanted protein-based vaccines.This study will involve two vaccines registered in Brazil and a protein-based adjuvantedvaccine candidate, SCB-2019/Clover. Protein-based adjuvanted vaccines have the advantageof being from a known and licensed technology that can produce high quantities of vaccineat reasonable Costs of Goods. Protein-based adjuvanted vaccines have also been shown tobe highly immunogenic, both in the context of COVID-19 (2,5) and other licensed vaccines(6), with long persistence of immunity and protection.Over 80% of the Brazilian population above the age of 18 years have received a fullprimary vaccination and another 7% at least one dose of vaccine. The overall boostercoverage is about 48% (64% of the adults) (7). Anvisa has authorized 1st and 2nd boosterdoses of various vaccines in line with the MoH policy which was last updated in March2022. It can be speculated that, like in other geographies, a third booster will berecommended soon, especially to at risk populations and in the scenario of highcirculation of the Omicron BA.5 strain.This study will explore the immunogenicity, safety and reactogenicity of a booster doseof various platforms in fully primed individuals regardless of the number of boosterdoses they have received prior to the enrollment in the study.This mimics the "real world scenario" at vaccination centers where individuals withdifferent background vaccination schemes show up for "a booster". It would facilitatelogistics of immunization substantially if vaccines for boosting, independent of theimmunization status, could be interchangeable with respect to safety/reactogenicity andimmunogenicity. This study will enroll fully-primed individuals (2 doses of either PfizermRNA or Oxford/AZ/Fiocruz or Sinovac/Butantan or 1 dose of Janssen vaccine) who havereceived their last vaccine dose at least 4 months prior to study entry and who havereceived either no booster, or 1 or 2 boosters. Individuals will be stratified in cohortsby number of boosters and then randomized to receive one of 3 booster vaccines(AstraZeneca/Fiocruz, Pfizer/Wyeth, SCB-2019/Clover).
Not Provided
Biological: SCB-2019/Clover
SCB-2019/Clover Vaccine
Biological: AstraZeneca/Fiocruz
AstraZeneca/Fiocruz Vaccine
Biological: Pfizer/Wyeth
Pfizer/Wyeth Vaccine
Inclusion Criteria:
1. Male or female ≥18 years of age.
2. Individuals are willing and able to comply with study requirements, including all
scheduled visits, vaccination, laboratory tests, and other study procedures.
3. Individuals are willing and able to give an informed consent, prior to screening.
4. Individuals must have completed vaccine priming, regardless of vaccine regimen.
Primary vaccination and previous booster scheme data will be annotated as patient
history.
5. Interval between last dose and current study dose of a minimum of 4 months and a
maximum of 24 months (to optimize candidate participation).
6. Healthy participants or participants with pre-existing medical conditions who are in
a stable medical condition. A stable medical condition is defined as disease not
requiring significant change in therapy or hospitalization for worsening disease
during the 3 months before enrollment.
7. Female participants are eligible to participate in the study if not pregnant, not
breastfeeding, and at least 1 of the following criteria apply:
- Women of non-childbearing potential;
- Women of childbearing potential (WOCBP) must have a negative urine pregnancy
test prior to study vaccination. A confirmatory serum pregnancy test may be
conducted at the investigator's discretion. They must be using a highly
effective licensed method of birth control during the study, until 90 days
after the study vaccination.
Exclusion Criteria:
Participants are excluded from the study if any of the following criteria apply:
1. Individuals with fever >37.5°C (axillary), or any acute illness at baseline (Day 0)
or within 3 days prior to randomization. Participants meeting this criterion may be
rescheduled within the relevant window. Febrile participants with minor illnesses
can be enrolled at the discretion of the investigator.
2. Self-reported confirmed COVID-19 infection, through RT-PCR or lateral flow test, in
the last 4 weeks.
3. Individuals who did not complete the primary vaccination scheme for any licensed
COVID vaccine or plan to receive another COVID-19 vaccine (other than the study
vaccines) during the study period, a drug for COVID-19 prevention or treatment
(e.g., drugs, monoclonal antibodies, such as Rituximab or any other anti-CD20
monoclonal antibodies during the study period.).
4. Individuals who have a history of severe adverse reaction associated with a vaccine
or severe allergic reaction (e.g., anaphylaxis, venal or arterial thrombosis,
thrombocytopenia) to any component of the study vaccines (Pfizer/Wyeth,
AstraZeneca/Fiocruz, CpG 1018, aluminum, or SCB-2019 components, as outlined in the
latest summary of product characteristics for Pfizer/Wyeth, AstraZeneca/Fiocruz, and
the IB for SCB-2019/Clover).
5. Individuals with capillary leakage syndrome or thrombosis with thrombocytopenia
syndrome
- TTS (possibly associated with vaccination with the AstraZeneca/Fiocruz
vaccine).
6. Individuals who had pericarditis or myocarditis (these pathologies may be associated
with the Pfizer/Wyeth vaccine, especially in young men).
7. Individuals with known bleeding disorder that, in the opinion of the investigator,
contraindicate intramuscular injection.
8. Individuals who have a history of malignancy within 1 year before screening
(exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ
of the cervix which have been cured, or other malignancies with minimal risk of
recurrence).
9. Individuals with any progressive or severe neurologic disorder, seizure disorder, or
history of Guillain-Barré syndrome.
10. Individuals who received treatment with immunosuppressive therapy in the last 90
days, including cytotoxic agents or systemic corticosteroids, or planned receipt
during the study period. If a short-term course of systemic corticosteroid
immunosuppressive dose has been used for the treatment of acute illness, the
participant should not be included in the study until corticosteroid therapy has
been discontinued for at least 15 days prior to first study vaccination.
If the participant has used an immunosuppressive dose of a depot corticosteroid,
intra-muscular or intra-articular, they must wait 60 days for inclusion in the
study. Inhaled nebulized, intra-articular, intrabursal, or topical (skin or eyes)
corticosteroids are permitted.
11. Individuals with autoimmune diseases, except: Hashimoto's thyroiditis, vitiligo,
psoriasis, lupus discord and alike; HIV-positive individuals and/or on HIV
treatment.
12. Individuals who have received any other investigational product within 30 days prior
to Day 0 or intend to participate in another clinical study at any time during the
conduct of this study.
13. Individuals who have received any other licensed vaccines within 14 days prior to
enrollment in this study or who are planning to receive any vaccine up to 28 days
after the last vaccination.
14. Individuals who have received treatment with Rituximab or any other anti-CD20
monoclonal antibodies within 9 months prior to Day 0 or planned during the study
period.
15. Administration of intravenous immunoglobulins and/or any blood products within 3
months prior to enrollment or planned administration during the study period.
16. Individuals with any condition that, in the opinion of the investigator, would
interfere with the primary study objectives or pose additional risk to the
participant.
17. Pregnancy.
18. Breastfeeding.
Centro de Estudos e Pesquisas em Moléstias Infecciosas - CEPCLIN
Natal, Rio Grande Do Norte, Brazil
Centro de Referência para Imunobiológicos Especiais - CRIE - UNIFESP
São Paulo, Brazil
Sue Ann C Clemens, MD, phD, Study Chair
University of Oxford