Effect of Bacillus Calmette-Guérin vaccination on the immunogenicity of the mRNA BNT162b2 COVID-19 vaccine in health care workers

At the time of writing, more than 85 million have been infected by the virus
and more than 1,8 million died in association with the virus. Next to the
global health, the coronavirus had a great impact on people*s daily life and
the global economy.

As of January 2021, the Netherlands is confronted with a second wave and the
country went back into lockdown. However, in the last weeks of 2020 there has
been the long-awaited news that Covid vaccines of several companies, among
which Pfizer, show about 95% efficiency. The vaccine has also been approved by
the EMA at 21 December 2020 and the Dutch vaccination program started January
8. Employees working in the COVID-19 frontline belong to the first group who
will get offered the vaccine.

In the course of the pandemic, it was unforeseeable when a Covid vaccine would
come available, thus researchers worldwide were searching for alternative
preventive measures. It has been shown for several years that the Bacillus
Calmette-Guérin (BCG) vaccination, a vaccine originally made against
tuberculosis, develops immunological memory in innate immune cells, a process
termed trained immunity. In addition, recent studies have suggested that COVID*
19 incidence and mortality rate are lower in countries where the BCG vaccine is
a part of the routine childhood immunisation schedule. Therefore, several
trials with different study populations have been set up to investigate whether
BCG can indeed protect against COVID-19. The first (interim) analyses will be
conducted within the next weeks.

Next to the unspecific protective effects of BCG, it is hypothesized that BCG
vaccination can enhance the immunogenicity of other vaccines. This has been
proven for the influenza and pertussis vaccines. BCG vaccination prior to
influenza or pertussis vaccinations results in a more pronounced increase and
accelerated induction of functional antibody responses. Our aim is to
investigate whether prior BCG vaccination can also enhance the immunogenicity
of the COVID*19 mRNA vaccine developed by BioNTech and Pfizer. By enhancing
antibody response through prior BCG vaccination, protection against COVID-19
may last longer after vaccination with the COVID-19 vaccine.

To determine the impact of prior BCG vaccination on the duration of
immunogenicity of the BioNTech/Pfizer mRNA COVID*19 vaccine.

A single center open label intervention study.

One group has been vaccinated with BCG in the past 12 months and will be
vaccinated with the COVID-19 vaccine from Pfizer/BioNTech. The other group has
never been vaccinated with BCG and will be vaccinated with the COVID-19 vaccine
from Pfizer/BioNTech.

In this study, patients will be asked to undergo a venipuncture and nasal
mucosal lining fluid sampling which are measurements of invasive nature.
Venipuncture may be painful and may cause hematoma. Obtaining mucosal lining
fluid by nasosorption may be experienced by participants as 'tickling' and
induce sneezing and/or tearing. However, sampling will be done by experienced
researchers and does not form any risk to the health of the subject.
Positive results from this study could lead to an increased efficacy of
COVID-19 vaccines and thereby help to combat the pandemic.