Induction of Cross-Reacting Antibodies Against the COVID-19 by BCG Vaccination in the Mouse Model

Abstract

It was reported that tuberculosis and BCG vaccination are potential tools for reducing the burden of COVID-19, mainly through the non-specific trained immunity. We have investigated whether BCG vaccination is able to induce cross-reacting antibodies against the SARS-CoV-2. We have tested the induced humoral immune responses against the SARS-CoV-2 Spike in the mouse model, after either BCG or rabies DNA-based vaccination alone or in Prime/Boost approach to COVID-19 DNA-based vaccination. We have demonstrated that BCG vaccination alone was able to induce cross-reacting antibodies to SARS-CoV-2 Spike. It can also boost the antibody response induced by a COVID-19 DNA-based vaccination. Hence, both BCG and latent tuberculosis infection can explain the lower burden of COVID-19 in developing countries, not only through the trained immunity but also by inducing cross-reacting antibodies. Furthermore, with the emergence of different COVID-19 variants, or eventually other Betacoronaviruses, the use of BCG vaccination can help against immune escapes of the current vaccines.

Fig. 1

Kinetics of humoral immune responses in mice. Mice of Group 1 and 2 were administered at Day0 50 µg or 100 µg of pCMV3ISS-CoV2S, respectively. Mice of Group 3 were administered at Day 0 50 µg of pCMV3ISS-GPV and 2 weeks later 50 µg of pCMV3ISS-CoV2S. Mice of Group 4 were administered at Day 0 the 1/10th of BCG human dose ant 2 weeks later 50 µg of pCMV3ISS-CoV2S. Mice of Group 5 were administered only at Day 0 the 1/10th of BCG human dose. Mice of Group 6 were administered only at Day0 50 µg of pCMV3ISS-GPV. Given results are optical density absorptions at 450 nm (OD). * Statistically significant compared to Group 1, filled circle statistically significant between days 90 and 28 in the same Group, both when p-values are lower than 0.05