L7: Vaccine Trials Phases I & II

Flashcards testing core vocabulary and key concepts from Lecture 7 on early phase vaccine clinical trials, study designs, objectives, and global research landscape.

Phase I Vaccine Trial:

(Safety & dose finding)

First-in-human clinical testing: assessing safety, tolerability, reactogenicity, dose selection, and immune response in a small cohort

Phase II Vaccine Trial

(expanded safety and immunogenicity) + optimal dose, formulation and schedule

An expanded clinical study typically 100’s of participants to further characterise safety, immunogenicity, dose, and schedule

– target populations or healthy volunteers

What is Vaccine Immunogenicity

How is it measures

What does immunogenicity not equate to

Evidence that a vaccine candidate stimulates an immune response

Measured by seroconversion and antibody titres

Does NOT equal definitive clinical efficacy

Seroconversion

The development of specific detectable antibodies in blood serum following vaccination, used as a primary marker for measuring immunogenicity.

Vaccine Efficacy

The measure of disease prevention assessed by comparing vaccine and placebo groups for clinical outcomes such as symptomatic cases, hospitalisations, or deaths.

Reactogenicity

Acute post-vaccination reactions and physical manifestations of the inflammatory response evaluated across dose and adjuvant groups during safety monitoring.

Adjuvant

A component included in a vaccine formulation to enhance or modify the body's immune response to the target antigen

– escalating antigen doses may be tested with & w/out adjuvant to justify progression

Phase I vax trials: typical design

Randomised

Double blinded

Placebo controlled

Dose comparison (multiple doses)

Adjuvant comparison (with & w/out)

Phase I vax trial: primary and secondary objectives

Primary: safety, tolerability, reactogenicity

Secondary: immunogenicity

Phase I vaccine trial: study schedule (5)

1) Screening: informed consent, eligibility checks.

2) Vaccination: pre-dose checks, intramuscular injection, acute observation

3) arly safety follow-up: diary review, symptoms, adverse events and safety labs

4) Final safety follow-up: safety window closure and ongoing AE review

5) Long-term follow-up: immunogenicity samples and selected safety monitoring

Phase I trials: common exclusion features when recruiting participants (4)

• Pregnant or breastfeeding

• Recent vaccination or active febrile illness

• Relevant travel restrictions

• Medical history that may affect safety interpretation

Phase I trials: common inclusion features when recruiting participants (3)

• Healthy adults, 18+

• Upper age cut-off or older-adult subgroup depending on protocol

• Ability to comply with visits, diaries and follow-up

Phase II eligibility

Expanding toward intended-use populations

• Older adults and those with stable comorbidities may be included where relevant

• Children, adolescents or pregnant women may be considered only with appropriate prior data, ethics and regulatory support.

Phase II objectives

Which preparation, dose and schedule has the best balance of safety, tolerability and immune response?

Is the immune response strong, durable and interpretable enough to justify a larger confirmatory Phase III program?