[jinnoman]

The repeat dose toxicity evaluations were conducted on COMIRNATY and a similar vaccine termed BNT162b2 (V8). COMIRNATY and BNT162b2 (V8) have identical amino acid sequences of the encoded antigens but COMIRNATY includes the presence of
optimized codons to improve antigen expression.

https://www.fda.gov/media/151733/download

Induction of S protein-specific immune responses is key to virus neutralization. Four different LNP-formulated, nucleoside-modified mRNA (modRNA) vaccine candidates targeting the S protein were evaluated in nonclinical rat studies as part of the joint Pfizer-BioNTech COVID-19 RNA vaccine development program.

Using the same mRNA backbone, two candidates encoded the RBD (BNT162b1 and BNT162b3), while the other two encoded the full-length S protein in its pre-fusion conformation (BNT162b2 [V8] and BNT162b2 [V9]).

BNT162b2 (V9) is the clinically approved Pfizer-BioNTech mRNA vaccine against COVID-19. It is a codon-optimized version of BNT162b2 (V8), which encodes for identical amino acid sequences but with improved protein expression and immunogenicity.

All four vaccine candidates were evaluated in two repeat dose toxicity studies in Wistar Han rats, which included a 3-week recovery phase. The objective of these studies was to evaluate the safety and immunogenicity of the vaccine candidates. This manuscript details the nonclinical study data for the four candidates and demonstrates the safety of this mRNA-LNP platform in the rat.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9965811/

COMIRNATY and BNT162b2 (V8) Similarities and Differences:

Both vaccines have identical amino acid sequences for the encoded antigens.
COMIRNATY includes optimized codons to improve antigen expression.

Vaccine Candidates in Nonclinical Rat Studies:

Four LNP-formulated, nucleoside-modified mRNA vaccine candidates were evaluated in rat studies.
Two candidates encoded the RBD (BNT162b1 and BNT162b3), while the other two encoded the full-length S protein in its pre-fusion conformation (BNT162b2 [V8] and BNT162b2 [V9]).

BNT162b2 (V9) - Clinically Approved Vaccine:

BNT162b2 (V9) is the clinically approved Pfizer-BioNTech mRNA vaccine against COVID-19.
It is a codon-optimized version of BNT162b2 (V8) with improved protein expression and immunogenicity.

Period 1
Period 1 title Overall period
Is this the baseline period? Yes
Allocation method Not applicable
Blinding used Not blinded

Arm title Phase 1: BNT162b1 10 mcg dose: 18-85 years of age

Investigational medicinal product name BNT162b1

Worldwide total number of subjects: 46934

Country: Number of subjects enrolled

Germany: 500
United States: 36461

https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-002641-42/results
j
Period 1
Period 1 title Overall period
Is this the baseline period? Yes
Allocation method Not applicable
Blinding used Not blinded

Arm title Phase 1: BNT162b1 10 mcg dose: 18-85 years of age

Investigational medicinal product name BNT162b1

Pharmaceutical forms Injection
Routes of administration Intramuscular use
Dosage and administration details 10 mcg: 250 mcg/0.5 mL

Arm title Phase 1: BNT162b1 20 mcg dose:18-85 years of age

Worldwide total number of subjects: 46934

Country: Number of subjects enrolled

Germany: 500
United States: 36461

https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-002641-42/results

Phase 2/3: BNT162b2 (30 mcg) >=16 years of age < > Phase 2/3: Placebo

started 21500 21351
completed 6954 10428
Not completed 14546 10923
Physician decision 35 31
Death 67 68
Unspecified 9647 3608
Lost to follow-up 1089 1402

Although the study was designed to follow #!$%@? for safety and efficacy for 2 years after the second dose, given the high vaccine efficacy, ethical and practical barriers prevent following placebo recipients for 2 years without offering active immunization, once the vaccine is approved by regulators and recommended by public health authorities. Assessment of long-term safety and efficacy for this vaccine will occur, but it cannot be in the context of maintaining a placebo group for the planned follow-up period of 2 years after the second dose.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745181/

Phase 2/3: To evaluate efficacy of prophylactic BNT162b2 against confirmed COVID-19 occurring from 7 days after second dose in subjects without evidence of infection before vaccination and in subjects with or without evidence of infection before vaccination; To define the safety profile of prophylactic BNT162b2 in the first 360 subjects randomized (Phase 2), all subjects randomized (Phase 2/3);

and subjects 12 to 15 years of age (Phase 3);

Number of subjects in period 5

Phase 3: BNT162b2 SA 30 mcg >=16 years of age

Started 333
Completed 228
Not completed 105
Consent withdrawn by subject 19
No longer meets eligibility criteria 8
Adverse event, non-fatal 1
Unspecified 24
Lost to follow-up 50
Protocol deviation 3

In order to further characterize booster responses induced by BNT162b2, 2 additional lower-dose booster groups have been added to the subset for evaluation of boostability and protection against emerging VOCs. An additional 5-µg or 10-µg dose of BNT162b2 will be given to approximately 144 Phase 3 #!$%@? approximately 5 to 7 months after their second dose of BNT162b2. An exploratory objective was added for Phase 3 #!$%@? to describe the immune response to a third dose of BNT162b2 or a third or fourth dose of BNT162b2SA at later time points to align with analyses and corresponding changes detailed in the statistical section. Allowed administration of BNT162b2 at Visits 101 and 102 to pregnant #!$%@? in certain circumstances.

Both companies are assessing two booster strategies: repeat vaccination with Comirnaty or with BNT162b2SA, a version of Comirnaty specific for the VOC B.1.351, first reported in South Africa. Comirnaty as a third dose should offer enough of an immunogenicity boost to protect against the original variant, experts noted. In fact, it could even supersede Comirnaty’s two-dose immunogenicity data, which would make room for any negative impact of VOCs such as B.1.351, they said.

However, experts argued that using BNT162b2SA as a booster in the wider population may be a better long-term protection investment. It would allow vaccine receivers to have a broader immunogenicity profile and perhaps heightened protection against a variety of variants, they added.

https://www.clinicaltrialsarena.com/comment/pfizer-biontechs-covid-19-vaccine-not-expected-to-require-a-booster-in-6-12-months-variant-of-concern-specific-shot-preferred/?cf-view