Table 1 The development of vaccine candidates in phase 3 clinical stage

Inactivated vaccines

The inactivated SARS-CoV-2 vaccine with aluminum hydroxide

Sinovac

Phase 3

2

0, 14 days

Phase 2 trial showed that two doses of 6 μg/0.5 mL or 3 μg/0.5 mL of the vaccine were well-tolerated and immunogenic in healthy adults, with 3 μg dose eliciting 92.4% seroconversion under day 0, 14 schedule and 97.4% under day 0, 28 schedule.

⁴³

Inactivated

Wuhan Institute of Biological Products/Sinopharm

Phase 3

2

0, 14 or 0, 21 days

Phase 2 trial showed that the GMTs of NAbs were 121 and 247 at day 14 after 2 injections in participants receiving vaccine on days 0 and 14 and on days 0 and 21, respectively. Moreover, 7-day adverse reactions occurred in 6.0% and 19.0% of the participants receiving injections on days 0 and 14 vs on days 0 and 21.

⁴⁴

Inactivated

Beijing Institute of Biological Products/Sinopharm

Phase 3

2

0, 14 or 0, 21 days

N/A

N/A

RNA vaccines

BNT162b1

Pfizer/Fosun Pharma/BioNTech

Phase 3

2

0, 28 days

Phase 1/2 study showed that the vaccine caused mild to moderate local and systematic symptoms in most vaccinators and geometric mean neutralizing titers after the 10 and 30 µg dose 2 reached 1.8- to 2.8-fold that of COVID-19 convalescent sera panel.

⁴⁸

mRNA-1273

Moderna/NIAID

Phase 3

2

0, 28 days

Phase 1 study reported that the two-dose vaccine series was not seriously toxic and it could elicit NAbs and Th1-biased CD4⁺ T-cell responses.

⁴⁹

Non-replicating vector vaccines

Adenovirus Type 5 Vector

CanSino Biological Inc./Beijing Institute of Biotechnology

Phase 3

1

N/A

Phase 2 trial showed that the vaccine at a dose of 5 × 10¹⁰ viral particles per mL was safer than the vaccine at 1 × 10¹¹ viral particles and elicited comparable immune response to it. However, high pre-existing Ad5 immunity reduced NAbs response and influenced T-cell immune response.

⁵⁵

ChAdOx1 nCoV-19

University of Oxford/AstraZeneca

Phase 3

1

N/A

Phase 1/2 trial reported that NAb responses were detected in 91% participants after a single dose when measured in MNA80 and in 100% participants when measured in PRNT50. After a booster dose, all participants had neutralizing activity. Local and systemic reactions, including pain, fever and muscle ache, could be reduced by paracetamol.

⁵⁹

Adeno-based (rAd26-S + rAd5-S)

Gamaleya Research Institute

Phase 3

2

0, 21 days

Phase 1/2 trial showed that administration of both rAd26-S and rAd5-S caused production of NAbs in 100% of participants on day 42 for both the lyophilized and frozen vaccine formulations. Cellular immune responses were detected in all participants at day 28. Moreover, the pre-existing immune response to the vectors rAd26 and rAd5 did not influence the titre of RBD-specific antibodies.

⁵⁷

Ad26COVS1

Janssen Pharmaceutical Companies

Phase 3

2

0, 56 days

Preclinical trials showed that a single immunization with an Ad26 vector encoding a prefusion stabilized S antigen triggered robust NAb responses and provided complete or near-complete protection in rhesus macaques. The immunogen contains the wildtype leader sequence, the full-length membrane-bound S, mutation of the furin cleavage site, and two proline stabilizing mutations.

⁶⁰