Evaluating Safety and Immune Response of Janssen, Moderna, Pfizer/BNT, and Novavax COVID-19 Vaccines for Same and Mixed Boosters in Adolescents and Adults Aged 12-64 With and Without HIV in Kenya, DRC, and Rwanda

NCT07408297 | Completed Phase 2 DMC

• 1 other identifier: VIBRI COVID-19-001/2021
• Study Type: interventional
• Target: 1,919
• Locations: 1 country
• Sites: 1

Brief Summary

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that emerged in the human population in Wuhan City, Hubei Province, China in December 2019. As of Jan 2022, there are over 328 million SARS-CoV-2 case worldwide and over 5.54 million deaths as a result of infection with SARS-CoV-2 (COVID-19). According to WHO Situation Report on 17 January 2022, Africa has 7 million confirmed cases with over 160, 804 deaths. The COVID-19 pandemic has caused global suffering, mortality, and severe economic pressures. There is thus a continued urgent global need to develop effective and safe vaccines and drugs to make them available at scale and equitably across all countries including in Africa. Despite the rapid successes in vaccine development and issuance of WHO Emergency Use Listings (EUL), the WHO SAGE Interim Reports and FDA Emergency Use Authorization (EUA) for COVID-19 vaccine evaluations have reported limitations on safety and efficacy data in certain populations including children and adolescents, pregnant women, and immunocompromised individuals such as those with HIV/AIDS who are at higher risk of severe COVID-19 disease. Africa is especially vulnerable in this respect given the high prevalence of HIV/AIDS in countries such as Kenya where the prevalence is over 20% in some places. The risk of recurring new waves of COVID-19 cases caused by Variants of Concern (VOC) exacerbates global public health crisis. A weak immune response to either single or two doses of primary vaccination against SARS-CoV-2 has been observed in immunocompromised population. Emerging data from observational studies consistently show waning immunity to primary vaccination for SARS-CoV-2 mutants, and a decline in vaccine effectiveness against SARS-CoV-2 infection and COVID-19 with time since primary vaccinations. These factors have led to consideration of the potential need for, and optimal timing of, booster doses for vaccinated populations. However, vaccine inequality, lack of availability of the same vaccine product used for primary vaccinations and unpredictable vaccine supply remain a challenge in LMIC. Consideration of heterologous COVID-19 vaccine to allow interchangeability (mix and match) use of vaccine products available in LMIC would therefore allow for programmatic flexibility. Based on a recent systematic review and meta-regression analysis, across the four WHO EUL COVID-19 vaccines with the most data (i.e., BNT162b2, mRNA 1273, Ad26.COV2.S and ChAdOx1-S \[recombinant\] vaccine), vaccine effectiveness against severe COVID-19 decreased by about 8% (95% confidence interval (CI): 4-15%) over a period of 6 months in all age groups. In adults above 50 years, vaccine effectiveness against severe disease decreased by about 10% (95% CI: 6 - 15%) over the same period. Vaccine effectiveness against symptomatic disease decreased by 32% (95% CI: 11 - 69%) for those above 50 years of age. For some inactivated vaccines (CoronaVac and COVID-19 vaccine BIBP), WHO has already issued the recommendation for the administration of an additional dose to those aged 60 years or older as part of the primary series to make initial immunity more robust. The FDA issued a EUA for the Janssen Ad26.COV.S1 COVID-19 vaccine for active immunization to prevent COVID-19 caused by SARS-CoV-2 in individuals 18 years of age and older. In September 2021, both the single dose and 2 dose Janssen COVID-19 vaccine regimens demonstrated high efficacy (79% protection (CI, 77%-80%) for COVID-19-related infections and 81 percent (CI, 79%-84%) for COVID-19-related hospitalizations. vs 94% (CI, 58%-100%) protection against symptomatic COVID-19 in the U.S. respectively. Furthermore, the safety profile of the vaccine remained consistent and generally well-tolerated in the 2 regimens. Finally, when a booster of the Janssen COVID-19 vaccine given 6 months after the single shot, antibody levels increased nine-fold one week after the booster and continued to climb to 12-fold higher four weeks after the booster. On June 14, 2021, Novavax reported the results of its PREVENT-19 pivotal Phase 3 trial of the NVX-CoV2373. The results showed an overall vaccine efficacy of 90.4% (95% CI: 82.9 - 94.6) in the US and Mexico. Sequenced data showed a vaccine efficacy was 93.2% (95% CI: 83.9 - 97.1) against Variants of Concern and Variants of Interest which represented 82% of cases. Studies of NVX-CoV2373 with Matrix-M adjuvant have demonstrated an acceptable safety and reactogenicity profile in adults ≥18 years of age. On December 20, 2021, the WHO issued interim recommendations and authorized under its emergency use listing (EUL) procedure, the NVX-CoV2373 COVID-19 vaccine developed by Novavax and Serum Institute of India. The pivotal phase 3 registration trial of the Moderna mRNA-1273 COVID-19 vaccine was conducted in the United States of America and involved about 30 000 participants aged 18 years or older with no known history of SARS-CoV-2 infection.

Conditions

COVID -19; SARS CoV 2 Infection

Keywords

Mix and match

Outcome Measures

Primary Outcomes (7)

• Solicited Local Adverse Events

  Occurrence of solicited local AEs (pain, redness, swelling)

  Within 7 days after booster vaccination

• Solicited Systemic Adverse Events

  Occurrence of solicited systemic AEs (fever, headache, fatigue)

  Within 7 days after booster vaccination

• Incidences of vaccine Related Serious Adverse Events

  Incidence of SAEs assessed as related to study vaccination

  Through study completion

• Immunogenicity Objective 1: Neutralizing Antibody Titer

  GMT of SARS-CoV-2 neutralizing antibodies measured by pVNA

  At Day 28 post-booster

• Immunogenicity Objective 2:Anti-Spike IgG Titer

  GMT of SARS-CoV-2 spike-specific IgG antibodies measured by ELISA

  At Day 28 post-booster

• Immunogenicity Objective 3: Fold Rise in Neutralizing Antibodies

  GMFR in neutralizing antibody titers from baseline to Day 28

  Baseline (Day 0) and Day 28

• Immunogenicity Objective 4: Fold Rise in Anti-Spike IgG

  GMFR in spike-specific IgG titers from baseline to Day 28

  Baseline (Day 0) and Day 28

Secondary Outcomes (14)

• Incidence of Unsolicited Adverse Events

  Through 28 days after booster vaccination.

• Incidence of Treatment-Emergent Adverse Events (TEAEs)

  From Day 0 (booster) to Day 85.

• Incidence of Adverse Events of Special Interest (AESIs)

  From Booster (Day 0) through study completion, an average of 1 year

• Incidence of All Serious Adverse Events (SAEs)

  From Day 0 through study completion, an average of 1 year

• Heterologous vs. Homologous Boost: Neutralizing Antibody Titer

  At Day 28 post-booster.

Other Outcomes (10)

• Incidence of Virologically Confirmed SARS-CoV-2 Infection

  From Day 28 post-booster through study completion, an average of 1 year

• Severity of Breakthrough SARS-CoV-2 Infection

  From Day 28 through study completion, an average of 1 year

• Time to Symptom Resolution

  From symptom onset through study completion, an average of 1 year

Study Arms (4)

Heterologous Novavax Boost

EXPERIMENTAL

Biological: Janssen Ad26COVS1; Biological: Pfizer-BioNTech vaccine COVID-19 vaccine; Biological: Inactivated Sinopharm or Sinovac COVID-19 vaccine

Homologous Janssen Boost

EXPERIMENTAL

Biological: Janssen Ad26COVS1

Heterologous Janssen Boost

EXPERIMENTAL

Biological: Pfizer-BioNTech vaccine COVID-19 vaccine; Biological: Inactivated Sinopharm or Sinovac COVID-19 vaccine

Homologous mRNA Boost

EXPERIMENTAL

Biological: Pfizer-BioNTech vaccine COVID-19 vaccine

Interventions

Janssen Ad26COVS1 BIOLOGICAL

Janssen Ad26COVS1 is formulated to contain recombinant, replication-incompetent adenovirus type 26 expressing the SARS-CoV-2 spike protein, citric acid monohydrate, trisodium citrate dihydrate, ethanol, 2-hydroxypropyl-β-cyclodextrin (HBCD), polysorbate-80, sodium chloride.

Heterologous Novavax Boost; Homologous Janssen Boost

Pfizer-BioNTech vaccine COVID-19 vaccine BIOLOGICAL

Pfizer-BioNTech COVID-19 vaccine, BNT162b2, is an mRNA vaccine encoding a P2 mutant spike protein (PS 2) and formulated as an RNA-lipid nanoparticle of nucleoside-modified mRNA (modRNA). BNT162b2 elicits a blunted innate immune sensor activating capacity and thus augments antigen expression.

Heterologous Janssen Boost; Heterologous Novavax Boost; Homologous mRNA Boost

Inactivated Sinopharm or Sinovac COVID-19 vaccine BIOLOGICAL

Sinopharm's BBIBP-CorV and Sinovac's CoronaVac are inactivated whole-virus COVID-19 vaccines. Both are produced by chemically inactivating (using beta-propiolactone) the whole SARS-CoV-2 virus (strain CN02 or similar) and then adsorbing the inactivated viral particles onto an aluminum hydroxide (alum) adjuvant. This traditional vaccine platform presents the immune system with the entire structural repertoire of the virus including spike, nucleocapsid, and membrane proteins in a non-replicating form, thereby inducing a broad antibody and cellular immune response against multiple viral antigens.

Heterologous Janssen Boost; Heterologous Novavax Boost

Eligibility Criteria

• Age: 12 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• \. Adolescent male or female aged ≥ 12 to 17 years at screening and adult male or female aged ≥ 18 to 64 years at screening (inclusive).
• \. Written informed consent (and assent if adolescent), after review of the consent form and having adequate opportunity to discuss the study with an investigator or a qualified designee. For participants who cannot read or write, the consent must be witnessed by a literate third party not involved in study conduct.
• \. Comply with study procedures, including potential home visits for COVID-19 follow-up.
• \. Has completed a primary homologous vaccination series at least 3 months prior to enrollment. Vaccinations allowed include:
• a) mRNA (Moderna mRNA-1273 or Pfizer/BNT) - primary series is 2 doses
• b) Adenovector 26 (Janssen Ad26COVS1) - primary series is 1 dose;
• c) Inactivated whole virus (Sinopharm-BIBP or Sinovac) - primary series is 2 doses;
• \. Female participants of childbearing potential (defined as any female who has experienced menarche and who is NOT surgically sterile \[i.e, hysterectomy, bilateral tubal ligation, or bilateral oophorectomy\] or postmenopausal \[defined as amenorrhea at least 12 consecutive months or documented plasma follicle-stimulating hormone level ≥40 mIU/mL\]) must agree to consistently use an effective method of contraception from enrolment and agree to continue adequate contraception until 12 weeks after vaccination:
• a. Condoms (male or female)
• b. Diaphragm with spermicide
• c. Cervical cap with spermicide
• d. Intrauterine device
• e. Oral or patch contraceptives
• f. Hormonal Contraceptives implants or injection e.g., Norplant®, Depo-Provera®.
• g. Abstinence, as a form of contraception, is acceptable if in line with the participant's lifestyle.

You may not qualify if:

• \. Use of a heterologous COVID-19 primary series at the platform level (mRNA, Adenovector and inactivated vaccine).
• \. Use of an extended primary vaccination series or prior booster with any SARS-COV2 vaccine.
• \. Any subject with prior Adverse Events of Special Interest Relevant to COVID-19 (see table 6).
• \. Unstable or Severe Chronic disease inclusive of:
• a. Hypertension (elevated blood pressure \[SBP\>180mmHg or DBP\>110mmHg\]). Note that participants can be retested once after resting or return on another day for retesting. Participants may also have anti-hypertensive medication adjusted and may be reassessed after at least 2 weeks.
• b. Congestive heart failure (CHF) stage 3 or greater or diagnosed cardiovascular disease that is not controlled using medication in the past 6 months.
• c. Chronic obstructive pulmonary disease (COPD) with a history of an acute exacerbations repeated in the past 2 years. Note: If participant has been stable the last 6 months and are not Gold stage 3 or greater, they may be included.
• d. Asthma stage 4 and/or unstable cases with asthma therapy adjustments in the past that 2 months.
• e. Type 1 or any type 2 diabetes (adult onset) of severe grade by history/medical review or with an HbA1c \> 8.5 in the last 6 months.
• f. Chronic kidney disease requiring dialysis or GFR \<30 (may use associated creatinine based on age and gender).
• g. Chronic hepatic disease with evidence of hepatic compromise by history/medical review. Includes known Hepatitis B or C.
• h. Chronic or serious neurological diseases (e.g. cerebrovascular disease (including transient ischemic attacks), autoimmune disorders, neurologic deterioration (including dementia), Guillain Barre syndrome).
• i. Any ongoing, symptomatic acute illness requiring medical or surgical care or chronic illness of severe grade or that is not stable over the past 6 months (at the discretion of the investigator).
• j. HIV Stage III/IV
• \. Cognitive impairment - congenital or acquired

Sponsors & Collaborators

• Victoria Biomedical Research Institute: lead
• Rinda Ubuzima, Rwanda: collaborator
• University of Kinshasa: collaborator
• Coalition for Epidemic Preparedness Innovations: collaborator

Study Sites (1)

Victoria Biomedical Research Institute

Kisumu, Kenya

Location

MeSH Terms

Conditions

COVID-19

Interventions

BNT162 Vaccine; sinovac COVID-19 vaccine

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

mRNA Vaccines; Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Recombinant Proteins; Proteins; Amino Acids, Peptides, and Proteins; Vaccines; Biological Products; Complex Mixtures; COVID-19 Vaccines; Viral Vaccines; Antigens; Biological Factors

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Parallel with multiple arms

Study Record Dates

• First Submitted: January 5, 2026
• First Posted: February 13, 2026
• Study Start: May 18, 2022
• Primary Completion: June 27, 2024
• Study Completion: June 27, 2024
• Last Updated: February 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

KE (1)