A comparison of COVID-19 Vaccine Candidates in the United States (September 2020)

Short summary / Key points:

Credit: JPMorgan Chase & Co
  • US Government has signed contracts to buy 800 million doses of vaccines for its citizens:
    • Pfizer & BNTX’s ‘BNT162’ vaccine
    • Astrazeneca’s ‘AZD1222’ vaccine
    • Moderna’s ‘mRNA-1273’ vaccine
    • GlaxoSmithKline and Sanofi’s vaccine (as of yet no name)
    • Novavax’s ‘NVX-CoV2373’ vaccine
    • Johnson and Johnson’s ‘Ad26.COV2.S’ vaccine
  • Several of these contracts include the option to acquire hundreds of millions more
  • Several trials will be finishing in October, with approval and rollout possible as soon as November
  • Healthcare professionals, high risk groups, and essential employees will be among first recipients in 2020
  • There are some differences appearing among these candidates which I will go into below

 

Pfizer/BioNTech’s BNT162b2:

“Immunogenicity of BNT162b1 and BNT162b2. Participants in groups of 15 were vaccinated with the indicated dose levels of either BNT162b vaccine candidate (n=12) or with placebo (n=3) on Days 1 and 21. Reponses in placebo recipients for each of the dosing groups are combined (P). The 28-day blood collection is 7 days after the second vaccination. Sera were obtained before vaccination (Day 1) and 21, and 28 days after the first vaccination. Day 35 is shown only for the 10 µg and 30 µg BNT162b1 (18–55 years) groups. Human COVID-19 convalescent sera (HCS, n=38) were obtained at least 14 days after polymerase chain reaction confirmed diagnosis and at a time when the donors were asymptomatic. b. 50% SARS-CoV-2–neutralizing geometric mean titers (GMTs). LLOQ is 20. Each data point represents a serum sample, and each vertical bar represents a geometric mean with 95% CI. The numbers above the bars are the GMCs or GMTs for the group. Arrows indicate timing of vaccination (blood draws were conducted prior to vaccination on vaccination days).”

BNT162b2 is Prizer/BioNTech’s most promising candidate (and most advanced, in terms of regulatory approval). Pfizer has began Phase III testing in the US with their 30μg dose (see below). They are on track for regulatory review by the end of October, with approval meaning the vaccine could roll out as early as November. They, along with Moderna, are among the most advanced (in terms of regulatory approval) US candidates.

Promising Phase I data has been reported, with the 10μg and 30μg doses providing  SARS-CoV-2 neutralization titers that were higher than those found in serum of recovered COVID-19 patients. They are moving on to Phase III testing with the 30μg dose, according to a July 27th press release1. The vaccine will involve 2 doses, 21 days apart2.

Some of the team’s discussion is included here:

“Previously reported data from vaccination of 18–55 year old adults with 10 μg or 30 μg of BNT162b1 suggested that it could be a promising COVID-19 vaccine candidate.2,5 Consistent with our strategy to evaluate several RNA vaccine candidates and make a data-driven decision to advance the candidate with the best safety and immunogenicity profile, we compared clinical data obtained after vaccination with BNT162b1,2,5 which encodes the RBD, or with BNT162b2, which expresses the full-length spike. The data set presented here guided our decision to advance BNT162b2 at the 30-μg dose level into the Phase 2/3, global safety and efficacy evaluation in participants 18–85 years of age.”3.

Astrazeneca’s AZD1222:

Astrazeneca’s most advanced candidate is the ChAdOx1 nCoV-19 vaccine (also called AZD1222). On August 15th, Astrazeneca published phase I/II data in The Lancet. 4

35/35 participants had neutralizing antibody responses (measured by PNRT) against nCoV-2019 after one dose. After a booster dose, it remained a 100% rate of neutralizing antibody response. This trial, to the best of my knowledge, did not publish quantifiable titers in experimental subjects compared to those in convalescent plasma of recovered COVID patients. They did publish a figure which graphically represented it (see right).

“Between April 23 and May 21, 2020, 1077 participants were enrolled and assigned to receive either ChAdOx1 nCoV-19 (n=543) or MenACWY (n=534), ten of whom were enrolled in the non-randomised ChAdOx1 nCoV-19 prime-boost group. Local and systemic reactions were more common in the ChAdOx1 nCoV-19 group and many were reduced by use of prophylactic paracetamol, including pain, feeling feverish, chills, muscle ache, headache, and malaise (all p<0·05). There were no serious adverse events related to ChAdOx1 nCoV-19. In the ChAdOx1 nCoV-19 group, spike-specific T-cell responses peaked on day 14 (median 856 spot-forming cells per million peripheral blood mononuclear cells, IQR 493–1802; n=43). Anti-spike IgG responses rose by day 28 (median 157 ELISA units [EU], 96–317; n=127), and were boosted following a second dose (639 EU, 360–792; n=10). Neutralising antibody responses against SARS-CoV-2 were detected in 32 (91%) of 35 participants after a single dose when measured in MNA80 and in 35 (100%) participants when measured in PRNT50. After a booster dose, all participants had neutralising activity (nine of nine in MNA80 at day 42 and ten of ten in Marburg VN on day 56). Neutralising antibody responses correlated strongly with antibody levels measured by ELISA (R²=0·67 by Marburg VN; p<0·001).”  5

On August 31st, The NIH announced that the AZN1222 phase III clinical trial in the United States had begun and will involve 2 doses 28 days apart, with the placebo being a saline injection (as opposed to a meningitis vaccine, like the UK trials). Their goal is to enroll approximately 30,000 patients.

 

On September 9th, AZN announced a halt in the study to investigate an adverse event in a participant6. Previously, results were expected in November.

Moderna’s mRNA-1273:

Moderna’s age-stratified data, as presented to the Advisory Committee on Immunization Practices on August 26th. Key points include the comparability of titers across all age groups, as well as median titers for 56+ y/o individuals being above those in convalescent sera.

Moderna’s most advanced candidate (in terms of regulatory review) is the mRNA-1273 vaccine. Moderna’s phase I trial for this candidate involved doses of 25μg, 100μg, and 250μg, in two doses, 28 days apart. The results of this trial were described on July 14 in a NEJM article7.

According to these results, as of day 43, the 25μg dose and 100μg dose provided neutralizing antibody titers (measured by PNRT) that were 2.1x and 4.1x those found in serum of recovered COVID-19 individuals, respectively. The PNRT of the 250μg dose was not evaluated, for reasons I honestly couldn’t find. It’s possible the data on those individuals just wasn’t ready yet.

As of July 27th, Moderna is moving forward to phase III testing of approximately 30,000 individuals at its 100μg dose8. Their vaccine involves 2 doses, 28 days apart. Like Pfizer/BioNTech, this vaccine is on track for review by late October, with possible rollout in November.

On August 26th, Moderna updated the ACIP with age-stratified date from its phase I trials. The data was positive and supported immunity in all age groups, most importantly in elderly individuals (an absolutely critical need of these vaccines is the ability to build immunity in the elderly). Their slides are available here. A screenshot from one of their slides is above and to the right.

Moderna’s vaccine is notably more stable than the Pfizer/BioNTech vaccine. The latter requires transportation at -70 degrees C. Moderna’s requires -20 degrees C. Moderna’s can also be refrigerated for 7 days after being removed from its -20 degree C vessel (compared to 24 hours of stability for Pfizer’s). This difference is significant when considering distribution in healthcare systems with less advanced infrastructure (this includes both rural US areas as well as developing nations).

Novavax’s NVX-CoV2373:

Vaccine responses compared favorably with
HCS in patients with clinically significant disease

Novavax released phase I data in early August and is moving toward phase III trials at the end of September to the best of my knowledge (“end of September” is what I was told by an employee at one of their clinical sites).

Here is a slide deck presented to stakeholders on August 4th. Here is the pre-print of their early results, published August 6th.

Early Novavax trials were investigating the vaccine’s performance as well as how Novavax’s proprietary adjuvant, Matrix-M1, affects response. 

Their 5μg dose + 50μg adjuvant dose (5+M; 5+M column, right) developed neutralizing titers at levels roughly 4x those found in convalescent serum. I’m unsure what method they used to quantify this.

Based on information here it appears they’re moving forward with their 5μg/ 50μg adjuvant in 2 doses, 21 days apart.

GSK/Sanofi:

They are behind other manufacturers, just recently launching their phase I/II trials in the US (as of September 8th). On this timeline, phase III trials will begin at the end of 2020, with regulatory approval possible in the “first half of 2021”9.

Johnson & Johnson subsidiary Janssen’s ‘Ad26.COV2-S’:

This candidate published nonhuman primate (Rhesus monkey) data at the end of July10. Phase I/II trials are currently underway and pending regulatory approval, they may begin phase III trials by the end of September11. Their ClinicalTrials.gov page lists the phase III trial as already being underway, but I believe this is a mistake.

Inovio’s INO-4800:

I will update this with more info when  I have time. As of now, approaching p3 testing. No publication of p1/2 results, although a brief summary of data has been available to investors. Vaccine has displayed both cell-mediated and humoral responses. See image on right.

INO-4800 notably has a long shelf life… doesn’t require refrigeration. A consequence of the fact that it is a DNA vaccine. Makes it attractive for developing healthcare systems or rural use in developed systems.

 

 

I will update this article with more info when I have time.

 
  1. https://www.businesswire.com/news/home/20200727005800/en/Pfizer-BioNTech-Choose-Lead-mRNA-Vaccine-Candidate
  2. https://clinicaltrials.gov/ct2/show/NCT04368728?term=NCT04368728
  3. Walsh, E. E., Frenck, R., Falsey, A. R., Kitchin, N., Absalon, J., Gurtman, A., … & Swanson, K. A. (2020). RNA-Based COVID-19 Vaccine BNT162b2 Selected for a Pivotal Efficacy Study. medRxiv.
  4. Folegatti, P. M., Ewer, K. J., Aley, P. K., Angus, B., Becker, S., Belij-Rammerstorfer, S., … & Dold, C. (2020). Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. The Lancet.
  5. Folegatti, P. M., Ewer, K. J., Aley, P. K., Angus, B., Becker, S., Belij-Rammerstorfer, S., … & Dold, C. (2020). Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. The Lancet.
  6. https://twitter.com/RebeccaDRobbins/status/1303452507641839616
  7. Jackson, L. A., Anderson, E. J., Rouphael, N. G., Roberts, P. C., Makhene, M., Coler, R. N., … & Pruijssers, A. J. (2020). An mRNA vaccine against SARS-CoV-2—preliminary report. New England Journal of Medicine.
  8. https://www.nih.gov/news-events/news-releases/phase-3-clinical-trial-investigational-vaccine-covid-19-begins
  9. https://www.gsk.com/en-gb/media/press-releases/sanofi-and-gsk-selected-for-operation-warp-speed-to-supply-united-states-government-with-100-million-doses-of-covid-19-vaccine/
  10. Mercado, N. B., Zahn, R., Wegmann, F., Loos, C., Chandrashekar, A., Yu, J., … & He, X. (2020). Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques. Nature, 1-11.
  11. https://www.jnj.com/single-dose-of-johnson-johnson-covid-19-vaccine-candidate-demonstrates-robust-protection-in-pre-clinical-studies

Leave a Reply

Your email address will not be published. Required fields are marked *