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Immunotherapy of COVID-19 with Bacille Calmette - Guerin: Where is the missing red herring?
1Department of Veterinary Microbiology, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, India.
Insights
The Bacille Calmette–Guérin (BCG) vaccine may reduce COVID-19 severity. Combining BCG with Purified Protein Derivative (PPD) could enhance immune responses for COVID-19 prevention and treatment by boosting anti-viral lymphocytes.
Area of Science:
- Immunology
- Vaccinology
- Infectious Disease
Background:
- Lower Coronavirus Disease 2019 (COVID-19) morbidity and mortality observed in populations with high Bacille Calmette–Guérin (BCG) vaccination rates.
- Previous research demonstrated that conjugating Purified Protein Derivative (PPD) to tumor cells enhances anti-tumor immunity in BCG-primed mice.
- A proposed mechanism involves PPD-pulsed, activated T-cells boosting anti-tumor responses by activating PPD-specific helper T-cells and lymphokine secretion.
Purpose of the Study:
- To explore the potential application of the BCG-PPD prime-boost strategy for COVID-19 immunoprophylaxis and immunotherapy.
- To investigate methods for enhancing anti-viral immune responses against SARS-CoV-2 using BCG and PPD.
Main Methods:
- Activation of autologous anti-coronavirus lymphocytes in vitro using inactivated virus or mitogens (e.g., Concanavalin A) to express Major Histocompatibility Complex (MHC) class II molecules.
- Pulsing activated lymphocytes with PPD for carrier targeting in vivo.
- Administration of PPD-pulsed, activated lymphocytes to patients previously vaccinated or recently primed with BCG.
Main Results:
- The strategy aims to achieve selective in vivo amplification of specific anti-viral lymphocytes.
- This amplification is expected to mount a robust immune response capable of clearing the virus and curing COVID-19.
- Conjugating antigens to PPD and administering to BCG-primed individuals may offer immunoprophylaxis against COVID-19.
Conclusions:
- The BCG-PPD system holds promise as a prime-boost strategy for both preventing and treating COVID-19.
- Purified Protein Derivative (PPD) may play a crucial role as a carrier in BCG-based COVID-19 immunotherapy.
- Further research is warranted to validate the efficacy of this approach in clinical settings.
Abstract:
Coronavirus Disease 2019 (COVID-19) morbidity and mortality was found to be less severe in countries where Bacille Calmette - Guerin (BCG) vaccination of the population is carried out. Conjugating Purified Protein Derivative (PPD) onto tumour cells and injecting into BCG primed mice was found to enhance anti-tumour immune response. We had proposed earlier that in vitro activated autologous anti-tumour T-cells bearing Major Histocompatibility Complex (MHC) II on their surface, if pulsed with PPD and re-infused in a BCG - primed patient, can activate PPD - specific helper T-cells and the focused secretion of lymphokines like the IL-2 can selectively amplify the antitumor T-cell response by their proliferation and activation in a specific manner bypassing the suppression exerted by the anti-idiotypic and suppressor cells. The prime - boost strategy with the BCG-PPD system can also be applied to the immunoprophylaxis and immunotherapy of COVID-19. The autologous anti-Corona virus B and T lymphocytes can be activated in vitro by inactivated virus or mitogens like Concanavalin A to express MHC class II molecules on their surface and pulsed with PPD for carrier targeting in vivo. Such PPD - pulsed activated (MHC-II+ve) anti-viral lymphocytes if transfused back into a patient already vaccinated with BCG during childhood or primed with BCG during adulthood 2 weeks before transfusion, could lead to a high magnitude of selective in vivo amplification of specific anti-viral lymphocytes, which can mount adequate and appropriate immune response to get rid of the virus and cure the patient from COVID-19. Conjugating antigens to PPD and injecting into BCG primed humans may also be helpful for immunoprophylaxis against COVID-19. Thus, PPD may prove to be the red herring in the BCG therapy of COVID-19.
