Rapid development of an inactivated vaccine for SARS-CoV-2

Authors: Qiang Gao et al.

Link to paper: https://www.biorxiv.org/content/10.1101/2020.04.17.046375v1

Journal/ Pre-Print: bioRxiv preprint

Tags: Vaccines

Research Highlights 

1. PiCoVacc, an inactivated SARS-CoV2 vaccine candidate, elicits neutralising antibodies that are effective against 10 different representative SARS-CoV2 strains in mouse and rat models.

2. PiCoVacc provides complete protection against SARS-CoV2 in rhesus macaques by eliciting a humoral response.

3. PiCoVacc, at doses up to 3 x 6ug, is safe for use in rhesus macaques, with no antibody-dependent enhancement observed.

Summary 

PiCoVacc is an inactivated SARS-CoV2 vaccine candidate. In mice and rats, PiCoVacc induces antibodies targeting the S protein, which are able to neutralise 10 representative strains of SARS-CoV2. Immunisation of rhesus macaques also elicits neutralising antibodies. A high dose of PiCoVacc protected animals from disease upon SARS-CoV2 challenge with no vRNA in the pharynx and lungs at day 7 and no histological evidence of pneumonia. PiCoVacc showed no antibody-dependent enhancement nor immunopathological effects at either dosage. This study demonstrates the protective efficacy and safety of PiCoVacc in rhesus macaques and offers a viable vaccine candidate against SARS-CoV2 to enter Phase I clinical trials.

Impact for SARS-CoV2/COVID19 research efforts

Develop a vaccine for SARS-CoV2/COVID19

· This study provides a viable vaccine candidate against SARS-CoV2 for use in Phase I clinical trials.

Study Type

· In vivo study 

Strengths and limitations of the paper

Novelty: Describes PiCoVacc, a novel inactivated SARS-CoV2 vaccine, which is shown to have protective efficacy and to be safe in rhesus macaques. At the high dose, PiCoVacc completely protects against SARS-CoV2 infection, and in both doses no antibody-dependent enhancement is observed.

Standing in the field: This is one of the first studies to demonstrate efficacy and safety from a SARS-CoV2 inactivated vaccine. PiCoVacc is one of a few SARS-CoV2 vaccine candidates that have entered Phase I clinical trials.

Appropriate statistics: No statistical analysis is described and no p values provided, despite some of the data being labelled as significant.

Viral model used: SARS-CoV2 strains isolated from 11 hospitalised patients worldwide.

Translatability: This study demonstrates protective efficacy and safety of PiCoVacc in rhesus macaques. It is therefore a viable vaccine candidate and entered phase I clinical trials on 16 April.

Main limitations:

· The authors provide no proof of inactivation of the virus in PiCoVacc.

· In the rhesus macaque efficacy studies, the sample size is n=4. This is too small to confer statistical significance to the results.

· Some decisions and data in the study are unclear. The timing of vaccination of rhesus macaques is unclear, i.e. it is stated that immunisations are given on days 0, 7 and 14, however it is also stated that the viral challenge is introduced on “day 22 (one day after the third immunisation)”. Other uncertainties include: the reason behind the use of CN2 as the vaccine strain, and in figure 3F which macaque group ‘mild interstitial pneumonia’ specimens are taken from.

· The viral challenge is given one day after the last immunisation, which is too soon to accurately represent natural infection.

· More longer-term data would be required to describe if the antibody response is long-lasting in rhesus macaques.