• Disposition and Demographics

• Safety- Reactogenicity 

• Safety- Adverse Events and Shifts in Laboratory Values

• Immunogenicity 

BNT162b1/BNT162b2 Results

• 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

- 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

Carnegie Mellon University

- mRNA-1273 (NCT04405076) Vaccine 
- BNT162b1/BNT162b2/BNT162b3 (NCT04368728) Vaccines
- INO-4800 (NCT04336410) Vaccine
- NCT04334980 Vaccine

Nucleic Acid Vaccines in Clinical Trial for COVID-19

Mulligan, M. J., Lyke, K. E., Kitchin, N., Absalon, J., Gurtman, A., Lockhart, S. P., . . . Jansen, K. U. (2020). Phase 1/2 Study to Describe the Safety and Immunogenicity of a COVID-19 RNA Vaccine Candidate (BNT162b1) in Adults 18 to 55 Years of Age: Interim Report. MedRxiv. doi:10.1101/2020.06.30.20142570
Link: https://www.medrxiv.org/content/10.1101/2020.06.30.20142570v1

Phase 1/2 Study to Describe the Safety and Immunogenicity of a COVID-19 RNA Vaccine Candidate (BNT162b1) in Adults 18 to 55 Years of Age: Interim Report

- mRNA-1273 is capable of triggering the adaptive immune response. This mRNA essentially codes for the viral spike (S) glycoprotein that is involved in receptor recognition with ACE2 receptors in host cells.
- Uses lipid nanoparticle dispersion that contains mRNA encoding  the stabilized prefusion SARS-CoV-2 spike protein 
- Pre-clinical trials: Rhesus macaque - administration of either 10 or 100 micrograms of the mRNA-1273 showed successful induction of type 1 helper T-cells (Th1)
- In phase 2 of clinical trials and planning on phase 3 later July.
-Supports a two dose (second administration) method of vaccination.

mRNA-1273 COVID-19 Vaccine by ModernaTX, Inc. 

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

INO-4800 targets the MERS coronavirus Spike protein. The nucleic acid vaccine by attaching to the receptor-binding site and neutralizing the epitopes. The vaccine has initiated a humoral and T-cell response as well as a spike in antibodies which function via competitive inhibition of the ACE2 receptor which the novel coronavirus also binds to. NCT04336410 is optimized through electroporation.

INO-4800 (NCT04336410) by Inovio Pharmaceuticals

This "bacTRL-Spike oral DNA vaccine encoding S of SARS-CoV-2" is under Phase 1 trial.

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