EFFECTIVENESS, SAFETY AND IMMUNOGENICITY OF THE HALF DOSE OF THE VACCINE ChadOx1 nCoV-19 (AZD1222) for COVID-19

Conditions

SARS-CoV-2

Keywords

vaccines, immunity, covid-19

Brief summary

This study is clinical trial (intervention study with external comparison group) to test vaccination with reduced dose (half dose) of ChAdOx1 nCoV-19 (AZD1222), in a 2-dose schedule with an interval of 8 weeks, including all adults aged 18 to 49 years from Viana city - Espírito Santo (ES)/Brazil, on the incidence of new cases over 12 months following treatment, compared to an external group from same state and adjusted for socio-demographic and epidemiological variables.

Detailed description

This study is clinical trial (intervention study with external comparison group) to test vaccination with reduced dose (half dose) of ChAdOx1 nCoV-19 (AZD1222), in a 2-dose schedule with an interval of 8 weeks, including all adults aged 18 to 49 years from Viana city - Espírito Santo (ES)/Brazil, on the incidence of new cases over 12 months following treatment, compared to an external group from same state and adjusted for socio-demographic and epidemiological variables. Cellular and humoral immunity will be studied in a representative sub-sample compared to an external reference group (cohort of health workers) vaccinated with standard dose. The outcomes will be evaluated at 28 days after the second dose and follow-up after 6 months and 12 months. The main outcome will be to decrease in 60% the incidence of new cases over 6 months after receiving the vaccine. The clinical epidemiological variables will be obtained from e-SUS VS, e-SUS notifica and datasus: number of cases, number of deaths with specific ICD for covid-19, number of hospital admissions for covid-19; number of ICU admissions for the treatment of SARS, total number of tests (RT-PCR) performed and positive. The cellular and humoral immune response will be assessed by viral neutralization assay (neutralizing antibody test), serological assay by chemiluminescence, determination of specific IgM and IgG profiles, measurement of systemic soluble factors (chemokines, cytokines and growth factors), stimulation antigen-specific peripheral blood mononuclear cells in vitro and investigation of memory T and B lymphocytes and intracytoplasmic cytokines. It is estimated to include 29,637 people in the study, to reach 85% vaccination cover of individuals aged 18-49 years. The subsample size immunogenicity test is 600 individuals from the eligible population, estimating losses of 15% and study power of 90%, alpha error of 1%. The hypothesis of the study is that the reduction in the incidence of covid-19 and the cellular and humoral immune response achieved with a half dose will be similar to the reduction expected with the standard dose.

Medeiros-Junior NF, Gouvea MDPG, Camacho LAB, Villela DAM, Lima SMB, Schwarcz WD, Azevedo AS, Neto LFP, Domingues CMAS, Fantoni RNDS, Forechi L, Ruchdeschel T, Albertino LF, Pereira M, Rizzi RB, Muniz SM, Santos HCD, de Oliveira Roza TL, Oliveira YGP, Dias LH, Miyamoto ST, Tapia KRL, Lyra DGP, Jubini JD, Burian APN, Moulaz IR, Araújo MF, Tort LFL, Oliveira ACA, Oliveira Prado R, Pereira AAS, Miranda VHS, Speziali E, Costa-Pereira C, Alves CC, Carvalho KRA, Dos Santos LM, Oliveira-Carvalho N, Oliveira G, Santos TMAFD, Figueiredo ACC, Costa-Rocha IA, Campi-Azevedo AC, Peruhype-Magalhães V, Garcia CC, Siqueira MM, Antonelli LRDV, Coelho-Dos-Reis JGA, Teixeira-Carvalho A, Mill JG, Martins-Filho OA, Valim V.

2025-10-30

10.3390/vaccines13111113

Interventions

BIOLOGICALHalf dose of ChAdOx1 nCoV-19 (AZD1222)

Vaccination with reduced dose (half dose) of ChAdOx1 nCoV-19 (AZD1222), in a 2-dose schedule with an interval of 8 weeks, including all adults aged 18 to 49 years, from non-priority groups, from Viana city - Espírito Santo (ES)/Brazil.

BIOLOGICALStandard dose of ChAdOx1 nCoV-19 (AZD1222)

Vaccination with standad dose of ChAdOx1 nCoV-19 (AZD1222), in a 2-dose schedule with an interval of 8 weeks, in external cohort of health workers aged 18 to 49 years.

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

PREVENTION

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 49 Years

Healthy volunteers

Yes

Inclusion criteria

\- residents of Viana, Espírito Santo, aged between 18 and 49 years

Exclusion criteria

* Pregnant women; * History of severe allergic reaction (anaphylaxis) to any previously administered vaccine; * Having received another vaccine in the last 14 days; * Belonging to a priority risk group for vaccination, as per the PNI recommendations; * Have fever or flu-like symptoms; * Have previously received any vaccine for covid-19 at any time; * Recent diagnosis of covid-19 with onset of symptoms 28 days before vaccination; * Disorders of coagulation and use of anticoagulants.

Design outcomes

Primary

Measure	Time frame	Description
Incidence of new cases	12 months	Incidence of new cases over 12 months following treatment

Secondary

Measure	Time frame	Description
Number of deaths	12 months	Number of deaths with specific ICD for covid-19
number of hospital admissions	12 months	number of hospital admissions for covid-19
number of intensive care unit (ICU) admissions	12 months	number of intensive care unit (ICU) admissions for the treatment of SARS
number of tests (RT-PCR)	12 months	number of tests (RT-PCR) performed and positive
Viral Neutralization Assay	4 and 8 months	Neutralizing antibody titers will be expressed by the ability of antibodies to neutralize up to 50% the number of plaques (PRNT50). Title \> 1:50 will be considered positive.
serological assay	8 and 10 months	Serological test by chemiluminescence. Results are expressed in U/mL and data interpretation will be done as follows: \<0.8 U/mL = non-reactive sample; ≥0.8 U/mL = reactive sample.
IgG	8 and 10 months	Determination of specific IgG profile. Results will be expressed in fluorescence intensity or pg/ml.
systemic soluble factors	8 and 10 months	Dosage of soluble systemic factors (chemokines, cytokines and growth factors). Results will be expressed in pg/ml.
Antigen-specific stimulation of peripheral blood mononuclear cells	10 and 12 months	Antigen-specific stimulation of peripheral blood mononuclear cells in vitro. The results will be expressed in percentage positive frequency for a specific cell phenotype.
Lymphocyte investigation	10 and 12 months	Investigation of memory T and B lymphocytes. The results will be expressed in percentage positive frequency for a specific cell phenotype.
Cytokine investigation	10 and 12 months	Investigation of intracytoplasmic cytokines. The results will be expressed in percentage positive frequency for a specific cell phenotype.
IgM	8 and 10 months	Determination of specific IgM profile. Results will be expressed in fluorescence intensity or pg/ml.

Other

Measure	Time frame	Description
Adverse events	14 months	All adverse events will be followed up to establish severity and causal correlation. There will be surveillance of deaths and will be reported to the ethics committee.

Countries

Brazil

Contacts

Primary ContactValéria Valim, PhD

val.valim@gmail.com+5527999874665

Outcome results

None listed