BCG vaccination induces enhanced frequencies of memory T and B cells and dendritic cell subsets in elderly individuals

Background BCG vaccination is known to induce innate immune memory, which confers protection against heterologous infections. However, the effect of BCG vaccination on the conventional innate and adaptive immune cells subsets is not well characterized. Methods We investigated the impact of BCG vaccination on the frequencies of T cell, B cell, monocyte and dendritic cell subsets as well as total antibody levels in a group of healthy elderly individuals (age 60-80 years) at one month post vaccination as part of our clinical study to examine the effect of BCG on COVID-19. Results Our results demonstrate that BCG vaccination induced enhanced frequencies of central and effector memory CD4+ T cells and diminished frequencies of naïve, transitional memory, stem cell memory CD4+ T cells and regulatory T cells. In addition, BCG vaccination induced enhanced frequencies of central, effector and terminal effector memory CD8+ T cells and diminished frequencies of naïve, transitional memory and stem cell memory CD8+T cells. BCG vaccination also induced enhanced frequencies of immature, classical and activated memory B cells and plasma cells and diminished frequencies of naïve and atypical memory B cells. While BCG vaccination did not induce significant alterations in monocytes subsets, it induced increased frequencies of myeloid and plasmacytoid DCs. Finally, BCG vaccination resulted in elevated levels of all antibody isotypes. Conclusions BCG vaccination was associated with enhanced innate and adaptive memory cell subsets, as well as total antibody levels in elderly individuals, suggesting its potential utility in SARS-Cov2 infection by enhancing heterologous immunity. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT04475302 ### Funding Statement This work was supported by the Indian Council of Medical Research (ICMR). The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the Ethics Committees of ICMR-NIRT (NIRT-INo:2020010) All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All the reported data are available within the manuscript