Target Product Profile Analysis of COVID-19 Vaccines in Phase III Clinical Trials and Beyond: An Early 2021 Perspective

The coronavirus SARS-CoV-2, which causes Coronavirus disease 2019 (COVID-19), has infected more than 100 million people globally and caused over 2.5 million deaths in just over one year since its discovery in Wuhan, China in December 2019. The pandemic has evoked widespread collateral damage to societies and economies, and has destabilized mental health and well-being. Early in 2020, unprecedented efforts went into the development of vaccines that generate effective antibodies to the SARS-CoV-2 virus. Teams developing twelve candidate vaccines, based on four platforms (messenger RNA, non-replicating viral vector, protein/virus-like particle, and inactivated virus) had initiated or announced the Phase III clinical trial stage by early November 2020, with several having received emergency use authorization in less than a year. Vaccine rollout has proceeded around the globe. Previously, we and others had proposed a target product profile (TPP) for ideal/optimal and acceptable/minimal COVID-19 vaccines. How well do these candidate vaccines stack up to a harmonized TPP? Here, we perform a comparative analysis in several categories of these candidate vaccines based on the latest available trial data and highlight the early successes as well as the hurdles and barriers yet to be overcome for ending the global COVID-19 pandemic.

-At least 70 % protective efficacy against disease caused by COVID-19 in healthy adults.
-At least 70% efficacy (on population basis, with consistent results in the elderly).
-Endpoint may be assessed vs. disease, severe disease, and/or shedding/transmission -Rapid onset of protection (less than 2 weeks)(OB).
-Rapid onset of protection is less important (LT).
-Phase III clinical studies should include an immunogenicity arm in which serum and blood samples are collected and tested for antibody and cell-mediated immunity.
-A minimum serological correlate of protection should be determined based on the shortterm and long-term efficacy.
(f) Dose Regimen -----Two-dose 1 o immunization regimen with preference for short interval between doses (max 0-28 days) and with some protection / immune response considered to be protective after the first dose.
-Single-dose primary series (OB). Lower frequency (Yearly or less) of booster doses is preferred (LT).
-Single dose 0.5 ml or less, if injectable. A second boosting dose 4-8 weeks later, if necessary.

(g) Duration of Protection
-Follow-up at least one to two years to assess duration of protection and potential for vaccine-associated ERD as immune responses to the vaccine wane.
-Confers protection for at least 6 months without booster vaccination. Duration of protection may be inferred from immune kinetics, as well as documentation of breakthrough cases.
-Confers protection for at least 1 year.
---- -Higher storage temperatures and higher thermostability will greatly enhance vaccine distribution and availability, and are thus strongly preferred.
-Thermostable, not light sensitive. The stability of vaccine potency is durable >2 yrs at room temperature.

(j) Co-Administration with other Vaccines
-----Evidence on safety and immunogenicity when co-administered with influenza vaccines should be considered.
-Stand-alone product (OB) -Potential for coadministration with other vaccines that are typically administered in campaigns preferred (LT).
-The SARS-CoV-2 vaccine should not be administered with any other vaccine or it can be administered concomitantly with influenza vaccine at separate sites.
-Availability of sufficient doses at cost/dose that allows broad use, including in LMIC (LT).
-Cost of goods should be reasonable to governments of both high-and lowincome nations.
(m) Consistent Manufacture -Data on the manufacture of at least three commercial-scale batches are sufficient to support the validation of the manufacturing process.
-This testing can be incorporated into the design of an efficacy trial and does not need to be conducted in a separate study.

Storage and Stability
The Moderna COVID-19 Vaccine multiple-dose vials are stored frozen between -25º to -15ºC (-13º to 5ºF). Store in the original carton to protect from light.
Vials can be stored refrigerated between 2° to 8°C (36° to 46°F) for up to 30 days prior to first use.
Defrost in a refrigerator and store [2°C to 8°C (35°F to 46°F)] for up to 5 days (120 hours). Unpunctured vials may be stored between 8° to 25°C (46° to 77°F) for up to 12 hours.
After dilution, multiple dose vials of Pfizer-BioNTech COVID-19 Vaccine must be stored between 2°C to 25°C (35°F to 77°F) and used within 6 hours from the time of dilution. Figure S1 Clinical efficacy vs neutralization titer (NT) for each vaccine with available data.
Error bars show 95% CI from published studies. p=0.07 probability slope equals 0. Preliminary calculation weighting all results equally.