In the phase 2 trial, the percentage of people who reported adverse outcomes in each dose section were:

- medium dose at days 0 and 14: 6% 

- alum only at days 0 and 14: 14.3%

- medium does at days 0 and 21: 19% 

- alum only at days 0 and 21: 17.9%

Most common adverse reactions: injection site pain was the most common and fever was the second most common.

All adverse reactions were only reported within the first seven days of injection. (No adverse reactions reported within days 8 to 28.)

Safety Outcomes for the Inactivated Whole Virus Vaccine by Wuhan Institute of Biological Products Phase II Trial 

Effectiveness of immunogenicity was assessed by measuring the geometric mean titer of neutralizing antibody to live SARS-CoV-2, and the geometric mean titer of specific IgG antibody to whole SARS-CoV-2 antigen. 
- Neutralizing Antibody Outcomes
- Specific IgG Antibody Outcomes

Immunogenicity Outcomes for the Inactivated Whole Virus Vaccine by Wuhan Institute of Biological Products Phase II Trial

Figure 3. Antibody Responses 14 Days After the Second Dose in the Phase 2 Trial

Safety Profile:
- 7 days after injection, 15% of participants reported adverse reactions (6 or 25% in the high dose in phase 1, and 16 or 19% in medium dose at days 0-21 in phase 2 had the most adverse reactions)
- Most common adverse reaction was injection site pain, then fever
- All reactions were mild and did not require treatment

Method:
- Randomized and placebo-controlled; adults aged 18-59 (with no positive COVID-19 result)
- Phase 1: 96 healthy adults were assigned to aluminum hydroxide only or low, medium, and high doses of the vaccine
- Phase 2: 224 healthy adults were given either aluminum hydroxide only, or 5 microgram/dose of the vaccine in two groups (days 1-14 or 1-21)

Performance:
- Geometric mean titer of phase 1 at 14 days post-injection: 316 in low-dose, 206 in medium-dose, and 297 in high-dose
- GMT of phase 2 using medium dose: 121 (injections received on days 0 and 14) and 247 (injections received on days 0 and 21)
- Seroconversion: 95.8% in medium-dose group in phase 1; 97.6% in two phase two groups; none in aluminum hydroxide only group


Wuhan Institute of Biological Products Vaccine Specifics (phases 1+2)

- Safety Outcomes 
- Immunogenicity Outcomes 

Santa Clara University

The study aimed to investigate the safety and immunogenicity of an inactivated whole virus vaccine agains SARS-CoV-2. The results of Phase I and Phase II trials suggest that minimal adverse reactions were observed and that a multiple dose approach is needed. Non-human primate trials have been conducted, but large scale clinical trials in humans are needed to understand the efficacy and the potential for long-term adverse reactions.
- Methods
- Results
- Discussion

Inactivated Whole Virus vaccine by Wuhan Institute of Biological Products

Xia, S., Duan, K., Zhang, Y., Zhao, D., Zhang, H., Xie, Z., Li, X., Peng, C., Zhang, Y., Zhang, W., Yang, Y., Chen, W., Gao, X., You, W., Wang, X., Wang, Z., Shi, Z., Wang, Y., Yang, X., … Yang, X. (2020). Effect of an Inactivated Vaccine Against SARS-CoV-2 on Safety and Immunogenicity Outcomes: Interim Analysis of 2 Randomized Clinical Trials. JAMA, 324(10), 951–960. https://doi.org/10.1001/jama.2020.15543

Effect of an Inactivated Vaccine Against SARS-CoV-2 on Safety and Immunogenicity Outcomes: Interim Analysis of 2 Randomized Clinical Trials

Study Design and Participants:
- Trials conducted in Henan Providence, China
- Double-blind, randomized, placebo-controlled Phase I and Phase II trials
- Participants: aged 18 to 59 years, no history of SARS-CoV (on-site inquiry) or SARS-CoV-2 (serological and nucleic acid test)
- Phase I Design: 96 participants, 3 vaccine dose groups (low 2.5 μg, medium 5 μg, and high 10 μg antigen protein content per dose) and a control group (received aluminum hydroxide adjuvant only), ratio of vaccine to placebo was 3:1, received intramuscular injections on days 0, 28, and 56.
- Phase II Design: 224 participants, 2 schedule groups that both received the 5 μg vaccine (days 0 and 14, and days 0 and 21), the vaccine to placebo ratio was 3:1.
- Sequential enrollment and sentinel data were used to keep the participants safe. The low dose in Phase I was used first and monitored for 7 days for adverse reactions. The medium dose group only received vaccines if there were no vaccine-related reactions in those 7 days, and the same procedure was followed for the high dose group and the phase II medium dose vaccinations. 

Methods

Results for the Inactivated Whole Virus vaccine by Wuhan Institute of Biological Products Phase II Trial 

- The vaccine was well tolerated and produced no vaccine related serious adverse effects. The incidence rate was 15% among all participants, which was lower than other current vaccines in trial. This could mean that an inactivated whole virus vaccine is a safer option, or it could be influenced by the small sample sizes of the current stage of testing.
- The neutralizing antibody response results suggest that a longer interval between the first and second administration produced higher responses than a shorter interval. The observed increase in antibody titers after the second injection and again after the third suggest that a booster is needed for this vaccine. However, more time and information is needed to determine the exact intervals and times for booster administration.
- Comparison to other published COVID-19 vaccine trials showed that the PRNT assayed antibody titers were comparable to the other studies. There are some drawbacks as the assay method is different and some results could not be compared.
- Some studies have indicated that the antibody titers decline over time while others indicated that long-lasting memory T cells are still reactive years after exposure. There is not enough information about the vaccine yet to determine how long the antibodies last, so the participants will be followed up with in a year.


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