AntiBody response in Risk groups to COrona Vaccination treated in the Adrz hospital:

The SARS COV-2 pandemic has prompted the (bio)medical, pharmaceutical,
governmental, as well as global organizations such as the WHO, to quickly
develop safe and effective vaccines in order to control the outbreak, minimize
morbidity and mortality, and limit the societal and economic impact. . In the
Netherlands, the government has pre-ordered a number of vaccines from various
companies and currently (February 2021) two different vaccines, based on the
advice of the National Institute for Public Health and the Environment, are in
use and the vaccination process has started.
The two vaccines - BNT162b2 (provided by Pfizer Biontech ) and mRNA1273
(provided by Moderna)- are messenger RNA vaccines, encoding the S1 spike
protein of SARS-CoV-2. After injection, the vaccine particles bump into cells
and fuse to them, releasing mRNA. The cell*s molecules read its sequence and
build spike proteins. The mRNA from the vaccine is eventually destroyed by the
cell, leaving no permanent trace. Some of the spike proteins form spikes that
migrate to the surface of the cell and stick out their tips. The vaccinated
cells also break up some of the proteins into fragments, which they present on
their surface. These protruding spikes and spike protein fragments can then be
recognized by the immune system. When a vaccinated cell dies, the debris will
contain many spike proteins and protein fragments, which can then be taken up
by a type of immune cell called an antigen-presenting cell. The cell presents
fragments of the spike protein on its surface. When other cells called helper T
cells detect these fragments, the helper T cells can raise the alarm and help
marshal other immune cells to fight the infection.

Measurements performed to test the immunogenicity of the candidate vaccines:

Functional neutralizing antibodies to SARS COV-2 that are produced following
vaccination (against the spike glycoprotein and the receptor-binding domain)
are considered as potential biomarkers of protective efficacy (1). This is why
drug companies firstly performed Phase 1 studies to find the right vaccine and
its right dose based on such biomarker assays (2,3). For instance , the degree
of immunogenicity produced by BNT162b2 was measured as follows:
SARS-COV-2 serum neutralization assay and receptor-binding domain [RBD]-
binding or S1-binding IgG direct Luminex immunoassays were conducted before
the administration of vaccine or placebo, at 7 days and 21 days after the
first dose, and at 7 days (i.e., day 28) and 14 days (i.e., day 35) after
the second dose.

Protective efficacy in terms of infection risk

The efficacy of BNT162b2 and mRNA1273 has been underlined by two prospective
placebo-controlled randomized trials with large patients groups in order to
acquire a sufficient number of events after short follow up (4,5). The 2
studies however excluded the following patient groups:

mRNA1273
- Immunosuppressive or immunodeficient state, including human immunodeficiency
virus (HIV) infection, asplenia, and recurrent severe infections
- Has received systemic immunosuppressants or immune-modifying drugs for >14
days in total within 6 months prior to Screening (for corticosteroids >=20
milligram (mg)/day of prednisone equivalent).

BNT162b2
- Immunocompromised individuals with known or suspected immunodeficiency, as
determined by history and/or laboratory/physical examination
- Individuals who receive treatment with immunosuppressive therapy, including
cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune
disease, or planned receipt throughout the study

Apparently, the investigators either expected the vaccine to be less effective
in these patient groups and/or they may have been cautious with regards to
vaccination safety.

Currently, there are no data on the efficacy and safety of these vaccines in
patients using high dose steroids or other immunosuppressive agents, patients
with a solid or hematological malignancy and patients who have undergone a
solid organ or hematopoietic stem cell transplantation.

The Dutch Society of Hematology (NVvH) has issued a vaccination guideline,
which states that -irrespective of disease or therapy type- postponement is not
necessary if patients are requested to come by for vaccination
(https://hematologienederland.nl/covid-19/). Furthermore, The NVvH, as well as
the Dutch Society of Medical Oncology, the Dutch Nephrology Federation and the
Dutch Society of Gastroenterologists have collaborated with the National
Institute for Public Health in the preparation of a general guideline for
immunocompromised patients (
https://lci.rivm.nl/handleiding-covid-19-vaccinatie-van-immuungecompromitteerde-
patienten).

In general, succesful seroconversion and seroprotection depend on vaccine
immunogenicity and host cellular immunity, which could be poorer due to
underlying disease and/or immunosuppressive medication. There is no theoretical
basis for an increased risk of anaphylaxis.

In the coming months, immunocompromised patients treated in our hospital will
be requested to undergo vaccination if they comply with the National Institute
for Public Health guidelines.

For all subgroups, it is of utmost importance to assess the degree of
immunogenicity according to methods (similar to the ones) used in the original
Phase 1 and 2 studies.

We plan to prospectively monitor immunogenicity of BNT162b2 and mRNA1273 (
according to the measures used in the registration studies), efficacy and
toxicity in 5 different groups of immunocompromised patients:
Furthermore , we plan to prospectively monitor adverse effects and vaccine
efficacy (i.e. prevention of SARS CoV- 2 infection within a follow up period of
at least two years).

Control Group:
A control group comprising 10 healthy volunteers aged 18 years or older will
undergo the same study procedures, except for the monitoring of adverse vaccine
effects..

This a prospective observational study, which strives to provide insight in the
immunogenicity, toxicity and efficacy of two approved SARS CoV-2 vaccines in 5
subgroups of immunocompromised patients, treated in the Adrz Hospital.

Patient inclusion takes place prior to the first vaccination and the same
counts for the volunteers.

The following baseline data will be collected in the CRF:

Patient age
Patient sex
For which disease have the immunosuppressants been prescribed?
Outpatient medication used
Specification of systemic treatment and last date of administration

The study requires 4 hospital visits ( before vaccination and 3 weeks, 6 months
and 12 months after the second vaccination) for the collection of blood samples
(either to to be stored at -70 degrees or used directly, in case of the
cellular studies). Whenever possible, the research nurse will make sure that
regular blood withdrawals and blood withdrawals for the study take place at the
same time.

For registration of adverse events, patients will be requested to fill in a
toxicity questionnaire in the weeks following the first vaccination and in the
first 2 weeks following the second vaccination. Vaccination date and vaccin
name wlll be noted.

For the measurement of vaccine efficacy patients will remain in follow up for
at least 2 years, unless they either develop a SARS CoV-2 infection or pass
away beforehand..The patients will be asked at the 6 months` and 12 months`
visit whether they have developed a SARS CoV-2 infection. At 18 months` and 24
months` patients will be phoned with the same question. In case of a positive
answer the SARS CoV-2 test data will be retrieved from the laboratory. Written
informed consent for this has been given prior to study inclusion.

Burden:
Completion of 2 one page- questionnaires
4 hospital visits for blood withdrawal (whenever possible, the research nurse
will make sure that regular blood withdrawals and blood withdrawals for the
study take place at the same time)
2 phone calls with the research nurse

Risks:
There are none

Benefit:
No personal benefit
But the study provides insight in the benefit of vaccination in these patient
groups