Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Aug 4;7(32):eabg7181.
doi: 10.1126/sciadv.abg7181. Print 2021 Aug.

Effect of BCG vaccination on proinflammatory responses in elderly individuals

Nathella Pavan Kumar  1 , Chandrasekaran Padmapriyadarsini  2 , Anuradha Rajamanickam  3 , Shrinivasa B Marinaik  2 , Arul Nancy  3 , Srinivasan Padmanaban  2 , Nabila Akbar  2 , Manoj Murhekar  4 , Subash Babu  5
Affiliations

Effect of BCG vaccination on proinflammatory responses in elderly individuals

Nathella Pavan Kumar et al. Sci Adv. .

Abstract

We investigated the influence of Bacillus Calmette-Guérin (BCG) vaccination on the unstimulated plasma levels of a wide panel of cytokines, chemokines, acute-phase proteins (APPs), matrix metalloproteinases (MMPs), and growth factors in a group of healthy elderly individuals (age, 60 to 80 years) at baseline (before vaccination) and 1 month after vaccination as part of our clinical study to examine the effect of BCG on COVID-19. Our results demonstrated that BCG vaccination resulted in diminished plasma levels of types 1, 2, and 17 and other proinflammatory cytokines and type 1 interferons. BCG vaccination also resulted in decreased plasma levels of CC, CXC chemokines, APPs, MMPs, and growth factors. Plasma levels of the aforementioned parameters were significantly lower in vaccinated individuals when compared to unvaccinated control individuals. Thus, our study demonstrates the immunomodulatory properties of BCG vaccination and suggests its potential utility in nonspecific vaccination of COVID-19 by down-modulating pathogenic inflammatory responses.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1. BCG vaccination results in diminished plasma levels of pro- and anti-inflammatory cytokines.
(A) The plasma levels of type 1 cytokines, IL-1 family, and type 1 IFNs in BCG prevaccinated (M0) (n = 82) and M1 after vaccination (n = 82) and plasma levels of type 1 cytokines, IL-1 family, and type 1 IFNs in BCG-unvaccinated (UVC) (n = 55) and postvaccinated (M1) (n = 82) individuals are shown. (B) The plasma levels of proinflammatory cytokines in BCG prevaccinated (M0) (n = 82) and M1 after vaccination (n = 82) and plasma levels of proinflammatory cytokines in BCG-unvaccinated (UVC) (n = 55) and postvaccinated (M1) (n = 82) individuals are shown. (C) The plasma levels of anti-inflammatory cytokines in BCG prevaccinated (M0) (n = 82) and M1 after vaccination (n = 82) and plasma levels of anti-inflammatory cytokines in BCG-unvaccinated (UVC) (n = 55) and postvaccinated (M1) (n = 82) individuals are shown. The data are represented as scatter plots with each circle representing a single individual. For the analysis of M0 and M1, P values were calculated using the Wilcoxon matched-pair tests with Holm’s correction for multiple comparisons; for the analysis between UVC and M1, P values were calculated using the Mann-Whitney test with Holm’s correction for multiple comparisons.
Fig. 2
Fig. 2. BCG vaccination results in diminished plasma levels of chemokines.
(A) The plasma levels of CC chemokines in BCG prevaccinated (M0) (n = 64) and M1 after vaccination (n = 82) and plasma levels of CC chemokines in BCG-unvaccinated (UVC) (n = 55) and postvaccinated (M1) (n = 82) individuals are shown. (B) The plasma levels of CXC chemokines in BCG prevaccinated (M0) (n = 82) and M1 after vaccination (n = 82) and plasma levels of CXC chemokines in BCG-unvaccinated (UVC) (n = 55) and postvaccinated (M1) (n = 82) individuals are shown. The data are represented as scatter plots with each circle representing a single individual. For the analysis of M0 and M1, P values were calculated using the Wilcoxon matched-pair tests with Holms correction for multiple comparisons; for the analysis between UVC and M1, P values were calculated using the Mann-Whitney test with Holm’s correction for multiple comparisons.
Fig. 3
Fig. 3. BCG vaccination results in diminished plasma levels of APPs.
The plasma levels of APPs in BCG prevaccinated (M0) (n = 82) and M1 after vaccination (n = 82) are shown. Data are shown as line diagrams with each line representing a single individual. P values were calculated using the Wilcoxon matched-pair tests with Holm’s correction for multiple comparisons. The plasma levels of APPs in BCG-unvaccinated (UVC) (n = 55) and postvaccinated (M1) (n = 82) individuals are also shown. The data are represented as scatter plots with each circle representing a single individual. P values were calculated using the Mann-Whitney test with Holm’s correction for multiple comparisons.
Fig. 4
Fig. 4. BCG vaccination results in diminished plasma levels of MMPs.
The plasma levels of MMPs in BCG prevaccinated (M0) (n = 82) and M1 after vaccination (n = 82) are shown. Data are shown as line diagrams with each line representing a single individual. P values were calculated using the Wilcoxon matched-pair tests with Holm’s correction for multiple comparisons. The plasma levels of MMPs in BCG-unvaccinated (UVC) (n = 55) and postvaccinated (M1) (n = 82) individuals are also shown. The data are represented as scatter plots with each circle representing a single individual. P values were calculated using the Mann-Whitney test with Holm’s correction for multiple comparisons.
Fig. 5
Fig. 5. BCG vaccination results in diminished plasma levels of growth factors.
The plasma levels of growth factors in BCG prevaccinated (M0) (n = 82) and M1 after vaccination (n = 82) are shown. Data are shown line diagrams with each line representing a single individual. P values were calculated using the Wilcoxon matched-pair tests with Holm’s correction for multiple comparisons. The plasma levels of MMPs in BCG-unvaccinated (UVC) (n = 55) and postvaccinated (M1) (n = 82) individuals are also shown. The data are represented as scatter plots with each circle representing a single individual. P values were calculated using the Mann-Whitney test with Holm’s correction for multiple comparisons.
See this image and copyright information in PMC

Comment in

References

    1. Tay M. Z., Poh C. M., Renia L., MacAry P. A., Ng L. F. P., The trinity of COVID-19: Immunity, inflammation and intervention. Nat. Rev. Immunol. 20, 363–374 (2020). - PMC - PubMed
    1. Benn C. S., Netea M. G., Selin L. K., Aaby P., A small jab–a big effect: Nonspecific immunomodulation by vaccines. Trends Immunol. 34, 431–439 (2013). - PubMed
    1. Biering-Sorensen S., Aaby P., Lund N., Monteiro I., Jensen K. J., Eriksen H. B., Schaltz-Buchholzer F., Jorgensen A. S. P., Rodrigues A., Fisker A. B., Benn C. S., Early BCG-Denmark and neonatal mortality among infants weighing <2500 g: A randomized controlled trial. Clin. Infect. Dis. 65, 1183–1190 (2017). - PMC - PubMed
    1. Garly M. L., Martins C. L., Bale C., Balde M. A., Hedegaard K. L., Gustafson P., Lisse I. M., Whittle H. C., Aaby P., BCG scar and positive tuberculin reaction associated with reduced child mortality in West Africa. A non-specific beneficial effect of BCG? Vaccine 21, 2782–2790 (2003). - PubMed
    1. Nemes E., Geldenhuys H., Rozot V., Rutkowski K. T., Ratangee F., Bilek N., Mabwe S., Makhethe L., Erasmus M., Toefy A., Mulenga H., Hanekom W. A., Self S. G., Bekker L.-G., Ryall R., Gurunathan S., DiazGranados C. A., Andersen P., Kromann I., Evans T., Ellis R. D., Landry B., Hokey D. A., Hopkins R., Ginsberg A. M., Scriba T. J., Hatherill M.; C-040-404 Study Team , Prevention of M. tuberculosis infection with H4:IC31 vaccine or BCG revaccination. N. Engl. J. Med. 379, 138–149 (2018). - PMC - PubMed

Publication types

MeSH terms