Cross-resistance from other vaccines

Clinical Question

Do any vaccines provide cross-protection for the SARS-Cov-2 virus?

Key Findings

  • There is in vitro and non-coronavirus evidence to suggest that childhood vaccines such as MMR and BCG could impart partial immunity to the SARS-CoV-2 virus, however there is currently no clinical data supporting that claim.
  • Clinical trials are currently being done evaluating the effect of BCG and oral polio on the severity and transmissibility of COVID-19.

Summary of Information

There is scant data for this topic.
Unfortunately, the most salient paper we found, “Children’s Vaccines Do Not Induce Cross Reactivity against SARS‐CoV” does not appear to be of particularly high quality.
Authors performed ELISA to determine whether the sera collected 14 days after mice were immunized with various vaccines would react with the SARS-CoV antigen and found no significant differences between pre- and post-immunization serum reaction. T-cells from pre- and post- immunized mice were also collected, and they did not show significant difference in cross reactivity to the SARS-CoV antigen. Authors further tried giving mice multiple vaccinations, but sera still did not react with SARS-CoV antigen on ELISA. Authors do not specify what they used for SARS-CoV antigen.[1]

We also reviewed studies that used an MMR vaccine modified to express the SARS-CoV or MERS-CoV spike protein as a potential method for vaccination against SARS-CoV. We focused on the negative controls (unmodified MMR vaccine) to see whether there is *any* cross-reactivity even with the unmodified MMR.

  • While the sera of mice who were vaccinated with the modified MMR reacted with SARS-CoV antigen on ELISA, the sera of mice who received the unmodified vaccine did not.[2]
  • A similar study performed on mice with measles vaccine modified to express MERS-CoV-N also failed to demonstrate cross-reactivity in negative, unmodified controls to the MERS-CoV virus.[3]

BCG vaccine and all cause mortality

There are reports of clinical trials launching in the Netherlands of BCG vaccination as a protective measure against SARS-CoV-2 infection.[4] These are based on reports that BCG vaccination may reduce all-cause mortality in infants:

  • A 2016 review in the BMJ found reduction in all cause mortality in children under 5 years who received measles and BCG vaccination.[5]
  • In a 2018 study, BCG vaccine was given to healthy adults 28 days prior to giving them the live attenuated yellow fever vaccine. At 5 days post-yellow fever vaccine, the yellow fever viral load as well as levels of circulating cytokines were lower in the BCG group. At 90 days post-vaccination, there was no difference in antibody titers to yellow fever between the group who got the BCG vaccine and the control group who did not receive the BCG vaccine (both groups received the yellow fever vaccine). Reduction in viral load and cytokine release was shown to be due to IL-1B mediated epigenetic changes to monocytes.[6]

Additionally, a clinical trial (BRACE) to assess whether BCG vaccination has protective effects against SARS-CoV-2 infection is underway in Melbourne, Australia. This trial aims to enroll 4,000 healthcare workers across Australia.[7]

Correlation between universal BCG vaccination policy and burden of Covid-19 illness?

A preprint study8 sought to answer this question by comparing deaths attributed to Covid-19 as well as SARS-Cov-2 cases in high income countries (USA, Italy, Netherlands etc) versus high income, and separately low income countries that have a policy of universal BCG vaccination. Although they find a correlation between universal BCG vaccination and lower mortality and infection rates, the data are not convincing, particularly since there is a relatively small number of countries without universal BCG vaccination. Furthermore, current estimates of deaths due to Covid-19 are likely inaccurate[8], and estimation of number infected is constrained by testing availability.

Author Information

Contributor: Priya Nayak PhD/MS4 UC San Diego School of Medicine
Completed on: March 25, 2020
Last updated on: April 30, 2020

Reviewed by: Gary Smithson
Reviewed on: April 11, 2020

This summary was written as part of the CoRESPOND Earth 2.0 COVID-19 Rapid Response at UC San Diego. For more information about the project, please visit http://earth2-covid.ucsd.edu

References

  1. Yu Y, Jin H, Chen Z, et al. Children's vaccines do not induce cross reactivity against SARS-CoV. J Clin Pathol. 2007;60(2):208-11.  [PMID:17264247]
  2. Escriou N, Callendret B, Lorin V, et al. Protection from SARS coronavirus conferred by live measles vaccine expressing the spike glycoprotein. Virology. 2014;452-453:32-41.  [PMID:24606680]
  3. Bodmer BS, Fiedler AH, Hanauer JRH, et al. Live-attenuated bivalent measles virus-derived vaccines targeting Middle East respiratory syndrome coronavirus induce robust and multifunctional T cell responses against both viruses in an appropriate mouse model. Virology. 2018;521:99-107.  [PMID:29902727]
  4. VriezeMar. 23 J de, 2020, Am 6:25. Can a century-old TB vaccine steel the immune system against the new coronavirus? Science | AAAS. https://www.sciencemag.org/news/2020/03/can-century-old-tb-vaccine-steel-immune-system-against-new-coronavirus. Published March 23, 2020. Accessed April 18, 2020.
  5. Higgins JP, Soares-Weiser K, López-López JA, et al. Association of BCG, DTP, and measles containing vaccines with childhood mortality: systematic review. BMJ. 2016;355:i5170.  [PMID:27737834]
  6. Arts RJW, Moorlag SJCFM, Novakovic B, et al. BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity. Cell Host Microbe. 2018;23(1):89-100.e5.  [PMID:29324233]
  7. Murdoch Children’s Research Institute to trial preventative vaccine for COVID-19 healthcare workers | Murdoch Children’s Research Institute. https://www.mcri.edu.au/news/murdoch-children%E2%80%99s-research-institute-trial-preventative-vaccine-covid-19-healthcare-workers. Accessed April 30, 2020.
  8. Brown E, Tran AB, Reinhard B, Ulmanu M. U.S. deaths soared in early weeks of pandemic, far exceeding number attributed to covid-19. Washington Post. https://www.washingtonpost.com/investigations/2020/04/27/covid-19-death-toll-undercounted/. Published April 27, 2020. Accessed April 30, 2020.
  9. Miller A, Reandelar MJ, Fasciglione K, Roumenova V, Li Y, Otazu GH. Correlation between universal BCG vaccination policy and reduced morbidity and mortality for COVID-19: an epidemiological study. medRxiv. March 2020:2020.03.24.20042937. doi:10.1101/2020.03.24.20042937