Local reaction: B1 (10-30ug)

• 18-55: mild to moderate pain at the injection site; more frequent post-dose-2 within 7 days

• 65-85: 92% reporting mild to moderate pain post-dose-1, and 75% post-dose-2.


Local reaction: B2 (10-30ug)

• Similar pattern observed

• 65-85: no swelling/redness observed


Systemic events: B1 (10-30ug) 

• 18-55: mild to moderate fever and chills post dose 1; 75% reporting fever post dose 2 of 30ug

• 65-85: overall milder reaction; fatigue and headache post-dose-1 or 2; 33% reporting fever post-dose-2

• Overall dose-dependent; greater post-dose-2


Systemic events: B2 (10-30ug) 

• 18-55: 17% reporting mild to moderate fever; small numbers reporting severe systemic events (fatigue, headache, chills, muscle pain, and joint pain) 

• 65-85: 8% reporting mild to moderate fever; no severe events observed 

• Overall milder than B1; 65-85 reporting systemic events similar to placebo group

Safety-Reactogenicity

18-55 YO

• B1: 50% reporting AE compared to 11.1% placebo group 

• B2: 16.7% reporting AE  

65-85 YO

• B1: 16.7% reporting AE 

• B2: 0% reporting AE


Adverse Events and Shifts in Laboratory Values

18-55YO

• B1 (10-30ug): antigen-binding IgG and neutralizing response boosted by dose 2

• B2 (10-30ug): ^

65-85YO

• B1 (10-30ug): lower responses than young

• B2 (10-30ug): ^

Overall 

• clear dose-dependent response between 10-20

• inconsistent response between 20-30 


Immunogenicity

This classification system categorizes 'BL', 'B1', and 'B2' into two distinct levels: a high level, represented by (↑), and a low level, represented by (↓).

Classification of BL, B1, and B2 Levels

Disposition and demographics of trial participants for the BNT162b1/BNT162b2 COVID-19 vaccine candidates (BioNTech/Fosun Pharma/Pfizer): • Age 18-55 (median: 35-37) and 65-85 (median: 68-69) years, split into younger and older cohorts • B1 and B2 candidates each dosed at 10ug, 20ug, or 30ug on a 2-dose schedule, 21 days apart • Participants predominantly white and non-Hispanic/non-Latinx • Among older participants, more female than male

Participant Disposition and Demographics for BNT162b1/BNT162b2 Vaccine Candidates

The Phase 1/2 evaluation of BNT162b1 and BNT162b2 reports results in four domains: participant disposition and demographics, reactogenicity, adverse events and laboratory-value shifts, and immunogenicity.

Keck Graduate Institute

Google

- Lipid nanoparticle-formulated, nucleoside-modified, mRNA vaccines that encode trimerized SARS-CoV-2 spike glycoprotein RBD.
- Currently in Phase 1/2 and testing 3 variations of the vaccines 
- Preliminary report on BNT162b1 available for phase 1/2

BNT162b1/BNT162b2/BNT162b3 Vaccines for COVID-19 by BioNTech/Fosun Pharma/Pfizer

Pfizer and BionTech are producing two vaccine candidates being studied in adults ranging from 18-55 and 65-85 in a placebo-controlled, observer-blinded dose-escalation study with 2 doses over 21-day intervals.
- BNT162b1: encodes a secreted trimerized SARS-CoV-2 receptor-binding domain
- BNT162b2: encodes perfusion stabilized membrane-anchored SARS-CoV-2 spike

The process is to select a single vaccine candidate and dose level for use.

BNT162b1/BNT162b2 from Pfrizer and BionTech

• Advance B2 at 30ug into Phase 2/3 with 18-85YO

• Milder systemic reactogenicity profile of B2, primarily 65-85

• Comparable immune response elicited 

• Lower reactogenicity (B2) may be due to the smaller size of the RNA constructs

• Note that immunogenicity decreased with age, yet still exceeded the base-line (GMT) of the convalescent serum panel

• Higer reactogenicity (B1) may be associated with an innate immune shut down of the host 

• B2 (full length spike) present greater diversity. 

• Limitations include: immunogenicity or safety beyond 7 days post dose-2 not available; uncertain importance of humoral and cellular immunity in protection from COVID-19; degree of protection against COVID also unknown. 

• Plan to address limitation with a bigger sample size, and diverse backgrounds

Discussions and Takeaways

Phase 1/2 Results for BNT162b1 and BNT162b2: Participants, Safety, and Immunogenicity

- Safety and immunogenicity of varying dose levels of BNT162b1 and Bnt162b2. The process was followed by testing the vaccine's safety through the proportion of participants exhibiting adverse events, 
- Immunogenicity assessment through a serum neutralization assay before the 7 and 21-day mark after Dose 1, and 21 days and 35 days after dose 2. 


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