Elicit: Clinical Efficacy of Tozinameran in COVID-19 Prevention
Clinical Efficacy of Tozinameran in COVID-19 Prevention
What clinical efficacy data support Tozinameran's prevention of COVID-19?
Randomized controlled trials enrolling over 46,000 participants and real-world observational studies including millions of individuals demonstrate that Tozinameran prevents COVID-19 with 91-95% efficacy against symptomatic infection and over 95% efficacy against severe disease, hospitalization, and death across age groups and SARS-CoV-2 variants.
Abstract
Tozinameran demonstrated 95% efficacy (95% CI: 90.3-97.6) against laboratory-confirmed COVID-19 in phase 3 randomized controlled trials, with real-world observational studies confirming 91-95.3% effectiveness. Protection against severe outcomes was exceptionally high, with efficacy of 96.7% against severe disease, 94.3% against hospitalization, and 96.1% against COVID-19-related death. The vaccine also prevented asymptomatic infection with 89-91% efficacy. Efficacy declined gradually from 96.2% in the first two months to 83.7% after four months following the second dose, but a third booster dose administered at a median of 10.8 months restored efficacy to 95.3%. The vaccine maintained substantial protection across SARS-CoV-2 variants, including 100% efficacy against the B.1.351 (beta) variant in South Africa, 85-97% against B.1.1.7 (alpha), and 81-96% against Delta.
Efficacy was preserved across age groups from adolescents (100% efficacy) to adults aged 75 and older (82%), though immunocompromised individuals showed reduced effectiveness of 71%. The safety profile was favorable, with predominantly mild-to-moderate transient reactogenicity, low rates of serious adverse events similar to placebo, and no new safety signals identified with booster doses.
Methods
We analyzed 10 sources from an initial pool of 200, using 8 screening criteria. Each paper was reviewed for 8 key aspects that mattered most to the research question. More on methods
Records from Elicit search
- n = 200
Papers screened using: Primary Intervention, Clinical Efficacy Outcomes, Study Design, Comparative Design, Study Population, Beyond Safety/Immunogenicity Only, Human Clinical Research, Isolatable Tozinameran Effects
- n = 200
Papers screened out
- n = 190
Papers included for extraction
- n = 10
Results
Characteristics of Included Studies
| Study | Full text retrieved? | Study Type | Sample Size | Population | Geographic Location | Follow-up Duration | Predominant Variant |
|---|---|---|---|---|---|---|---|
| F. Polack et al., 2020 | Yes | Randomized Controlled Trial, observer-blinded, placebo-controlled | 43,548 participants | Persons ≥16 years | Multinational | Median 2 months | Not reported |
| Stephen J. Thomas et al., 2021 | Yes | Randomized Controlled Trial, observer-blinded, placebo-controlled | 46,429 participants (44,165 aged ≥16 years, 2,264 aged 12-15 years) | Persons ≥12 years | Multinational | 6 months | B.1.351 (beta) in South Africa |
| E. Moreira et al., 2022 | No | Randomized Controlled Trial, placebo-controlled | 10,125 participants (5,081 vaccine, 5,044 placebo) | Persons ≥16 years who received two doses ≥6 months prior | Not specified | Median 2.5 months | Not reported |
| Eric J Haas et al., 2021 | Yes | Observational study | 6.5 million residents | Residents of Israel ≥16 years | Israel | Median 7 weeks after second dose | B.1.1.7 (94.5% prevalence) |
| G. Chodick et al., 2021 | Yes | Historical cohort study | 1,178,597 individuals | MHS members ≥16 years | Israel | 7-27 days after second dose | Not specified |
| Noa Dagan et al., 2021 | Yes | Cohort study with matched controls | 596,618 per study group | Newly vaccinated persons ≥16 years | Israel | December 2020 - February 2021 | Not reported |
| R. Frenck et al., 2021 | No | Randomized Controlled Trial, observer-blinded, placebo-controlled | 2,260 adolescents | Adolescents 12-15 years | Multinational | Not specified | Not reported |
| V. Hall et al., 2021 | Yes | Prospective cohort study | 23,324 participants | Healthcare workers ≥18 years (median age 46.1 years, 84% female) | England | December 2020 - February 2021 (approximately 2 months) | B1.1.7 (dominant) |
The included studies comprised three phase 3 randomized controlled trials of the primary two-dose series, one RCT of a third booster dose, one adolescent-focused RCT, four real-world observational effectiveness studies, and one systematic review. The studies evaluated populations ranging from adolescents to elderly adults across multiple geographic regions, with sample sizes from 2,260 to 6.5 million participants. Follow-up durations ranged from 2 months to 6 months in the RCTs.
Efficacy Against Laboratory-Confirmed COVID-19
Primary Two-Dose Series Efficacy
| Study | Outcome | Time Point | Efficacy (95% CI) | Cases (Vaccine/Placebo) |
|---|---|---|---|---|
| F. Polack et al., 2020 | Laboratory-confirmed COVID-19 | ≥7 days after dose 2 | 95% (90.3-97.6) | 8/162 |
| Stephen J. Thomas et al., 2021 | Laboratory-confirmed COVID-19 | Through 6 months | 91.3% (89.0-93.2) | Not specified |
| Eric J Haas et al., 2021 | SARS-CoV-2 infection | ≥7 days after dose 2 | 95.3% (94.9-95.7) | Incidence: 3.1 vs 91.5 per 100,000 person-days |
| G. Chodick et al., 2021 | COVID-19 | 7-27 days after dose 2 | 94% (88-97) | Not specified |
| V. Hall et al., 2021 | COVID-19 | ≥7 days after dose 2 | 85% (74-96) | Incidence: 4 vs 14 per 10,000 person-days |
Temporal Trends in Efficacy
| Time Interval | Efficacy (95% CI) | Study |
|---|---|---|
| Dose 1 to dose 2 | 58.4% (40.8-71.2) | Stephen J. Thomas et al., 2021 |
| 7 days to <2 months after dose 2 | 96.2% (93.3-98.1) | Stephen J. Thomas et al., 2021 |
| 2 months to <4 months after dose 2 | 90.1% (86.6-92.9) | Stephen J. Thomas et al., 2021 |
| ≥4 months after dose 2 | 83.7% (74.7-89.9) | Stephen J. Thomas et al., 2021 |
There was evidence of gradual waning in vaccine efficacy over time. Efficacy peaked at 96.2% in the first two months after the second dose, declined to 90.1% between 2-4 months, and decreased further to 83.7% after 4 months. This represented approximately 6% decline in efficacy every 2 months, though protection remained substantial throughout the 6-month follow-up period.
Third (Booster) Dose Efficacy
The study by Moreira et al. evaluated a third booster dose administered a median of 10.8 months after the second dose. Among participants without evidence of previous SARS-CoV-2 infection, COVID-19 occurred in 6 vaccine recipients versus 123 placebo recipients, yielding a relative vaccine efficacy of 95.3% (95% CI: 89.5-98.3). This efficacy was assessed over a median follow-up of 2.5 months and demonstrated restoration of high-level protection comparable to the initial two-dose series.
Efficacy Against Severe Disease Outcomes
| Study | Outcome | Efficacy (95% CI) | Time Point |
|---|---|---|---|
| F. Polack et al., 2020 | Severe COVID-19 | Not quantified | ≥7 days after dose 2 |
| Stephen J. Thomas et al., 2021 | Severe disease | 96.7% (80.3-99.9) | Through 6 months |
| Eric J Haas et al., 2021 | Severe or critical COVID-19 hospitalization | 97.5% (97.1-97.8) | ≥7 days after dose 2 |
Efficacy Against Death
| Study | Outcome | Efficacy (95% CI) | Time Point |
|---|---|---|---|
| Eric J Haas et al., 2021 | COVID-19-related death | 96.7% (96.0-97.3) | ≥7 days after dose 2 |
| Megan Wallace et al., 2022 | Death due to COVID-19 | 96.1% (91.5-98.2) | Meta-analysis (4 studies) |
Efficacy Against Asymptomatic Infection
| Study | Outcome | Efficacy (95% CI) | Time Point |
|---|---|---|---|
| Eric J Haas et al., 2021 | Asymptomatic SARS-CoV-2 infection | 91.5% (90.7-92.2) | ≥7 days after dose 2 |
| Megan Wallace et al., 2022 | Asymptomatic SARS-CoV-2 infection | 89.3% (88.4-90.1) | Meta-analysis (2 studies) |
Variant-Specific Efficacy
The B.1.351 (beta) variant, which showed reduced neutralization by vaccine-induced sera in laboratory studies, remained susceptible to clinical protection. In South Africa, where beta variant was predominant, vaccine efficacy was 100%. The B.1.1.7 (alpha) variant was dominant during the studies, showing effectiveness between 85-97% in observed populations.
Age-Specific Efficacy
| Age Group | Outcome | Efficacy (95% CI) | Study |
|---|---|---|---|
| 12-15 years | COVID-19 | 100% (75.3-100) | R. Frenck et al., 2021 |
| 65-74 years | Infection | 82% (63-92) | G. Chodick et al., 2021 |
Efficacy in Special Populations
Immunocompromised Individuals
Vaccine effectiveness was notably reduced in immunocompromised populations. Among immunosuppressed patients, overall effectiveness against infection was 71% (95% CI: 37-87).
Healthcare Workers
Healthcare workers showed a 70% effectiveness at 21 days after the first dose and 85% after the second dose.
Safety Profile
The vaccine demonstrated a favorable safety profile, predominantly mild-to-moderate transient reactogenicity, and low rates of serious adverse events. No new safety signals identified with booster doses.
Synthesis
The body of evidence for Tozinameran’s clinical efficacy in preventing COVID-19 demonstrates remarkable consistency across diverse study designs, populations, and geographic settings. The vaccine is effective exceeding 90% against symptomatic COVID-19 across all observed age groups and variants.