What is Vaccine Efficacy?
Vaccine efficacy (VE) is a measure of the proportionate reduction in disease attack rate among vaccinated individuals compared to unvaccinated individuals, as determined in controlled clinical trials. It answers the fundamental question: "By what percentage does this vaccine reduce the risk of disease?"
A vaccine efficacy of 90% means that vaccinated individuals had 90% fewer cases of the disease compared to the unvaccinated control group. This does not mean that 10% of vaccinated people will get sick; rather, it means the risk of infection is reduced by 90% relative to the baseline (unvaccinated) risk.
VE was first formalized by Greenwood and Yule in 1915 and remains the primary metric used to evaluate vaccine performance in randomized controlled trials (RCTs).
Vaccine Efficacy Formulas
Primary Formula
Where ARU = attack rate in the unvaccinated group and ARV = attack rate in the vaccinated group.
Equivalent Using Relative Risk
Absolute Risk Reduction
Number Needed to Vaccinate (NNV)
NNV represents the number of people who need to be vaccinated to prevent one additional case of disease. Lower NNV values indicate more impactful vaccines in the context of the disease's baseline incidence.
Interpretation Guide
| VE Range | Assessment | Interpretation |
|---|---|---|
| ≥90% | Excellent | Highly effective; dramatic reduction in disease risk |
| 70–89% | Good | Strong protection; most recipients well-protected |
| 50–69% | Moderate | Meaningful protection; may be sufficient for licensure |
| 30–49% | Low | Limited protection; may still have public health value |
| <30% | Minimal | Poor protection; generally considered insufficient |
| ≤0% | No efficacy | Vaccine provides no benefit or may increase risk |
Note: Regulatory agencies like the FDA typically require VE ≥50% for vaccine approval, though this threshold can vary based on disease severity and available alternatives.
Vaccine Efficacy Visualization
Efficacy vs Effectiveness
These two terms are often confused but have distinct meanings in vaccinology:
- Vaccine Efficacy: Performance under ideal, controlled conditions (randomized clinical trials). Participants are carefully selected, dosing schedules are strictly followed, and storage conditions are optimal.
- Vaccine Effectiveness: Performance under real-world conditions (observational studies). Reflects actual population-level impact, including imperfect adherence, diverse populations, varying storage conditions, and circulating variant strains.
Vaccine effectiveness is typically lower than efficacy because real-world conditions introduce variability. However, effectiveness data is more clinically relevant for public health decision-making.
How VE is Measured in Clinical Trials
Vaccine efficacy is determined through randomized controlled trials (RCTs), considered the gold standard for establishing causal relationships:
- Randomization: Participants are randomly assigned to receive either the vaccine or a placebo (control). This minimizes confounding variables.
- Blinding: Ideally double-blind, where neither participants nor investigators know who received the vaccine versus placebo, eliminating bias.
- Follow-up: Both groups are monitored over time for the occurrence of the target disease, using standardized case definitions.
- Analysis: Attack rates are calculated for each group, and VE is computed from the relative reduction.
Key considerations include adequate sample size (powered to detect meaningful differences), sufficient follow-up duration, and a high enough disease incidence in the population to generate enough cases for statistical significance.
Herd Immunity Threshold
Herd immunity occurs when a sufficient proportion of the population is immune, making disease spread unlikely and indirectly protecting unvaccinated individuals. The threshold depends on both the disease's basic reproduction number (R0) and the vaccine efficacy:
| Disease | R0 | Herd Immunity (100% VE) | Herd Immunity (90% VE) |
|---|---|---|---|
| Measles | 12–18 | 92–94% | >100% (not achievable) |
| Pertussis | 12–17 | 92–94% | >100% (not achievable) |
| COVID-19 (original) | 2–3 | 50–67% | 56–74% |
| Influenza | 1.5–2 | 33–50% | 37–56% |
| Polio | 5–7 | 80–86% | 89–95% |
Limitations of VE
- Does not capture severity reduction: A vaccine with moderate VE against infection may still dramatically reduce severe disease, hospitalization, and death
- Population-specific: VE may differ by age, sex, comorbidities, immunocompromised status, and geographic region
- Time-dependent: Efficacy often wanes over time as immunity decreases, necessitating boosters
- Variant-dependent: New pathogen variants may escape vaccine-induced immunity, reducing effectiveness
- Confounding in observational studies: Vaccine effectiveness estimates can be biased by healthy vaccinee effect, differential healthcare-seeking behavior, or prior immunity
- NNV depends on disease incidence: A highly efficacious vaccine may have a high NNV in low-incidence settings
Worked Example
In a clinical trial, 1,000 unvaccinated individuals had an attack rate of 10% (100 infected) and 1,000 vaccinated individuals had an attack rate of 1% (10 infected):
The vaccine is 90% efficacious. Vaccinated individuals have only 10% of the risk (RR = 0.10) compared to unvaccinated. The absolute risk is reduced by 9 percentage points, and approximately 11 people need to be vaccinated to prevent one case.
Frequently Asked Questions
What is a good vaccine efficacy?
Generally, VE ≥50% is considered the minimum threshold for regulatory approval by agencies like the FDA. VE ≥70% is considered good, and VE ≥90% is excellent. However, even vaccines with moderate efficacy (50–70%) can have enormous public health impact, especially for diseases with high incidence or severity.
What does 95% vaccine efficacy mean?
It means that among the study population, vaccinated individuals had 95% fewer cases of disease compared to unvaccinated individuals. It does NOT mean that 5% of vaccinated people will get the disease. The actual individual risk depends on the underlying attack rate in the population.
What is Number Needed to Vaccinate (NNV)?
NNV is the number of people who must be vaccinated to prevent one additional case of disease. It is the reciprocal of the absolute risk reduction. Unlike VE (which is relative), NNV accounts for the baseline disease risk, making it more useful for cost-effectiveness analysis and public health planning.
Can vaccine efficacy be negative?
Technically, yes. A negative VE would mean vaccinated individuals had a higher attack rate than unvaccinated. This could indicate antibody-dependent enhancement (ADE), an increased susceptibility to a different strain, or confounding in the study. Negative VE results are rare and typically prompt immediate investigation.
Why does vaccine effectiveness differ from efficacy?
Efficacy is measured under ideal trial conditions, while effectiveness reflects real-world performance. Real-world factors that reduce effectiveness include: improper storage (cold chain breaks), incorrect dosing intervals, diverse populations with varying immune responses, circulating variants different from trial strains, and waning immunity over time.