• AdelineBoettcher

COVID-19 Research Highlight: PiCoVacc (SARS-CoV-2) Safety and Efficacy in Mouse and Macaque Model

This is a highlight of the following article:

Development of an inactivated vaccine candidate for SARS-CoV-2 (Science, May 6, 2020)

This study describes the development and testing of a candidate SARS-CoV-2 vaccine, called PiCoVacc. Eleven samples of SARS-CoV-2 were collected from bronchioalveolar lavage fluid from patients from China, Italy, Switzerland, UK, and Spain. Of these 11 collected strains, one (termed CN2) was purified for vaccine development, and the other 10 (termed CN1, CN3-5, OS1-OS6) were used for preclinical challenge. The CN2 strain was passaged through Vero cells for efficient in vitro growth and expansion, and was then purified. To make the vaccine candidate, the purified virus was inactivated with beta-propriolactone.

In a first in vivo test, a group of 10 mice were injected with different PiCoVacc doses and with different levels of alum adjuvant. There were no adverse events in the mice at any dosage level. Six weeks after immunization, peak levels of IgG specific for the SARS-CoV-2 spike protein, with IgG detected that was specific to the receptor binding domain (RBD). Subsequent analysis showed that the antibodies produced were capable of viral neutralization.

Next, rhesus macaques were immunized three times at days 0, 7, and 14 with either 3 ug or 6 ug PiCoVacc doses. Spike-specific and neutralizing antibodies were detected at two weeks post-immunization. At day 22 (1 week after the third immunization), the animals were challenged with SARS-CoV-2 via intratrachial inoculation. At 7 days post inoculation, the monkeys had no detectable viral loads in the pharnyx or lung. Additionally, the researchers found that the amount of neutralizing antibodies decreased by approximately 30% by 3 days post infection, however antibody levels increase from days 5-7 to maintain neutralization.

Cytokine storms have been reported in patients with severe COVID-19 illness; and these cytokine storms are caused by excessive T cell responses. Therefore, the researchers next wanted to assess T cell responses to PiCoVacc. In their experiment, there were four groups: 1.5 ug PiCoVacc, 6 ug PiCoVacc, adjuvant (sham), and saline (placebo) (10 macaques per group) injected at day 0, 7, and 14. There were no changes in weight, appetite, or mental state in any group. Additionally, analysis of T-cell subsets in the blood (CD3+, CD4+, and CD8+) and cytokines (TNF-alpha, IFN-gamma, IL-2, IL-4, IL-5, and IL-6) showed no differences between the PiCoVacc and control groups. Histopathological assessment of organs such as lung, heart, and brain showed that there were no pathological differences between the groups. 

The authors anticipate that PiCoVacc could be entered in Phase I, II, and III trials in the later part of 2020. 

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