Ethical and policy considerations for COVID-19 vaccination modalities: delayed second dose, fractional dose, mixed vaccines

Wolff, Jonathan; Atuire, Caesar; Bhan, Anant; Emanuel, Ezekiel; Faden, Ruth R.; Ghimire, Prakash; Greco, Dirceu Bartolomeu; Ho, Calvin; Kochhar, Sonali; Moon, S. H.; Schaefer, Owen; Gooshki, Ehsan Shamsi; Singh, Jerome Amir; Smith, Maxwell J.; Thomé, Beatriz; Touré, Aissatou; Upshar, Ross

doi:10.1136/bmjgh-2021-005912

Cited by 6 publications

(5 citation statements)

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“…The program has delivered approximately one billion vaccine doses to 144 participating countries, but current production capacity for COVID-19 vaccines does not cover the global needs, thus delaying the end of the pandemic. We acknowledge that the use of fractional doses is associated with a number of programmatic and operational challenges which may hamper its roll-out, such as the possible need for special syringes, adjustments of diluent volumes, or exacerbated vaccine hesitancy due to lower antibody levels (22, 23). Nevertheless, we believe that these challenges are rather limited and can still be solved relatively quickly for the most part.…”

Section: Discussionmentioning

confidence: 99%

Safety and immunogenicity of a reduced dose of the BNT162b2 mRNA COVID-19 vaccine (REDU-VAC): a single blind, randomized, non-inferiority trial

Pannus

Depickère

Kemlin

et al. 2022

Preprint

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Background The use of fractional dose regimens of COVID-19 vaccines has the potential to accelerate vaccination rates in low-income countries. Dose-finding studies of the mRNA vaccine BNT162b2 (Pfizer-BioNTech) have suggested that a fractional dose induces comparable antibody responses to the full, licensed dose in people below 55 years old. Here, we report the safety and immunogenicity of a fractional dose regimen of the BNT162b2 vaccine. Methods REDU-VAC is a participant-blinded, randomised, phase 4, multicentre, non-inferiority study investigating safety, reactogenicity and immunogenicity of BNT162b2. Adults aged between 18 and 55 years, without uncontrolled co-morbidities, either previously infected or infection naive, were eligible and recruited at five sites across Belgium. Participants were randomly assigned to receive 20ug/20ug (fractional dose) or 30ug/30ug (full dose) of BNT162b2, administered intra-muscularly at a three-week interval. The primary endpoint was the geometric mean ratio (GMR) of serum SARS-CoV-2 anti-RBD IgG titres at 28 days post second dose between the reduced and the full dose regimens. The reduced dose was considered non-inferior to the full dose if the lower limit of the two-sided 95% CI of the GMR was greater than 0.67. The primary analysis was done on the per-protocol population, including infection naive participants only. Findings Between April 19 and April 23, 2021, 145 participants were enrolled in the study and randomized, of whom 141 were vaccinated and reached the primary endpoint. Participants were mostly female (69.5%), of European origin (95%), with a mean age of 40.4 years (SD 7.9). At 28 days post second dose, the geometric mean titre (GMT) of SARS-CoV-2 anti-RBD IgG of the reduced dose regimen (1,705 BAU/mL) was not non-inferior to the full dose regimen (2,387 BAU/mL), with a GMR of 0.714 (two-sided 95% CI 0.540-0.944). No serious adverse events occurred. Conclusions While non-inferiority of the reduced dose regimen was not demonstrated, the SARS-CoV-2 anti-RBD IgG titre was only moderately lower than that of the full dose regimen and, importantly, still markedly higher than the reported antibody response to the licensed adenoviral vector vaccines. These data suggest that reduced doses of the BNT162b2 mRNA vaccine may offer additional benefit as compared to the vaccines currently in use in most low and middle-income countries, warranting larger immunogenicity and effectiveness trials. The trial is registered at ClinicalTrials.gov (NCT04852861).

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Section: Discussionmentioning

confidence: 99%

Safety and immunogenicity of a reduced dose of the BNT162b2 mRNA COVID-19 vaccine (REDU-VAC): a single blind, randomized, non-inferiority trial

Pannus

Depickère

Kemlin

et al. 2022

Preprint

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“…In addition, if concerns about the efficacy or safety of the first vaccine were raised, changing to another vaccine type would be a reasonable option. 115 …”

Section: Administration Of Different First and Second Vaccine Dosesmentioning

confidence: 99%

COVID-19 vaccination challenges: A mini-review

Afshar

Barary

Hosseinzadeh

et al. 2022

Human Vaccines & Immunotherapeutics

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The emergence of SARS-CoV-2 has led to the infection of many people across the globe, over six million deaths, and has placed an unprecedented burden on public health worldwide. The pandemic has led to the high-speed development and production of vaccines against the COVID-19, as vaccines can end the pandemic. At the beginning of the program, vaccinations were initially targeted only at high-risk groups, such as the elderly, those with comorbidities, or healthcare workers. Although most of the mentioned populations have received the two recommended doses, limited resources have left many authorities with an effective vaccine undersupply. Therefore, policies have been implemented to manage the available doses of the vaccines more efficiently. As there is no universally agreed consensus on this topic, we discuss the different recommendations and guidelines regarding the time interval between the two vaccine doses and explain the different scenarios for applying the two doses.

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“…The program has delivered approximately one billion vaccine doses to 144 participating countries, but current production capacity for COVID-19 vaccines does not cover the global needs, thus delaying the end of the pandemic. We acknowledge that the use of fractional doses is associated with a number of programmatic and operational challenges which may hamper its roll-out, such as the possible need for special syringes, adjustments of diluent volumes, or exacerbated vaccine hesitancy due to lower antibody levels [23,24]. Nevertheless, we believe that these challenges are rather limited and can still be solved relatively quickly, with the important exception of vaccine hesitancy which already presents a major barrier to effective roll-out even without fractional dosing.…”

Section: Plos Global Public Healthmentioning

confidence: 99%

Safety and immunogenicity of a reduced dose of the BNT162b2 mRNA COVID-19 vaccine (REDU-VAC): A single blind, randomized, non-inferiority trial

Pannus

Depickère

Kemlin

et al. 2022

PLOS Glob Public Health

View full text Add to dashboard Cite

Fractional dosing of COVID-19 vaccines could accelerate vaccination rates in low-income countries. Dose-finding studies of the mRNA vaccine BNT162b2 (Pfizer-BioNTech) suggest that a fractional dose induces comparable antibody responses to the full dose in people <55 years. Here, we report the safety and immunogenicity of a fractional dose regimen of the BNT162b2 vaccine. REDU-VAC is a participant-blinded, randomised, phase 4, non-inferiority study. Adults 18–55 years old, either previously infected or infection naïve, were randomly assigned to receive 20μg/20μg (fractional dose) or 30μg/30μg (full dose) of BNT162b2. The primary endpoint was the geometric mean ratio (GMR) of SARS-CoV-2 anti-RBD IgG titres at 28 days post second dose between the reduced and full dose regimens. The reduced dose was considered non-inferior to the full dose if the lower limit of the two-sided 95% CI of the GMR was >0.67. Primary analysis was done on the per-protocol population, including infection naïve participants only. 145 participants were enrolled and randomized, were mostly female (69.5%), of European origin (95%), with a mean age of 40.4 years (SD 7.9). At 28 days post second dose, the geometric mean titre (GMT) of anti-RBD IgG of the reduced dose regimen (1,705 BAU/mL) was not non-inferior to the full dose regimen (2,387 BAU/mL), with a GMR of 0.714 (two-sided 95% CI 0.540–0.944). No serious adverse events occurred. While non-inferiority of the reduced dose regimen was not demonstrated, the anti-RBD IgG titre was only moderately lower than that of the full dose regimen and, importantly, still markedly higher than the reported antibody response to the licensed adenoviral vector vaccines. These data suggest that reduced doses of the BNT162b2 mRNA vaccine may offer additional benefit as compared to the vaccines currently in use in most low and middle-income countries, warranting larger immunogenicity and effectiveness trials. Trial Registration: The trial is registered at ClinicalTrials.gov (NCT04852861).

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Ethical and policy considerations for COVID-19 vaccination modalities: delayed second dose, fractional dose, mixed vaccines

Cited by 6 publications

References 0 publications

Safety and immunogenicity of a reduced dose of the BNT162b2 mRNA COVID-19 vaccine (REDU-VAC): a single blind, randomized, non-inferiority trial

Safety and immunogenicity of a reduced dose of the BNT162b2 mRNA COVID-19 vaccine (REDU-VAC): a single blind, randomized, non-inferiority trial

COVID-19 vaccination challenges: A mini-review

Safety and immunogenicity of a reduced dose of the BNT162b2 mRNA COVID-19 vaccine (REDU-VAC): A single blind, randomized, non-inferiority trial

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