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assesment Mink strains (003).DOCX
Dato 9. november 2020
Sagsnr. 2020110983
Implications of mutations in the spike protein of Danish mink-de-
rived SARS-CoV-2 isolates for vaccines and monoclonal antibody
therapeutics.
Purpose:
In this text, the data received from SSI regarding neutralization of a mink-derived SARS-CoV-2 isolate
carrying 4 simultaneous mutations in the spike protein by convalescent sera from patients early in the
Danish epidemic is evaluated, and risks for vaccine efficacy posed by such mink-derived virus strains
assessed.
Summary:
Danish mink-derived SARS-CoV-2 isolates have been reported to carry a number of mutations in the
spike protein, with some isolates having 4 simultaneous spike protein mutations.
Some of these mutations have been described as being mink-specific, i.e., as having originated in
mink.
However, data from GISAID (https://www.gisaid.org/) , the COVID-19 viral genome analysis pipeline at
Los Alamos, as well as scientific publications shows that viruses currently circulating in humans already
carry spike protein mutations which are identical or very similar to the spike protein mutations described
in Danish mink-derived viruses, albeit at very low frequency (<0.3% of circulating viruses in humans).
Therefore, the spike protein mutations observed in Danish mink-derived viruses should not be termed
mink-specific.
The higher frequency of certain spike protein mutations in mink-derived viruses than in human-derived
viruses is most likely caused by the virus' adaptation to replication in mink. Thus, the fitness of the mink-
derived viruses in humans is most likely reduced.
Only 2 of the mutations in the mink-derived viruses occur at spike protein sites targeted by neutralizing
antibodies:
 The receptor-binding site of the spike protein harboring the Y453F mutant is the most critical of
these, as it is able to induce particularly potent neutralizing antibody responses.
o However, the Y453F mutation is conservative, and not expected to have major impact
on receptor or antibody binding.
o In agreement with this, the Y453F spike mutation has been shown to have mild positive
effect on binding of the spike protein to the human ACE2 receptor (1,8-fold increase in
binding, likely within experimental error).
 The N-terminal domain of the spike protein is known also to be the target for neutralizing anti-
bodies, and the deletions of amino acids 69 and 70 in mink-derived viruses may impact antibody
binding.
o However, residues 69 and 70 in human-derived viruses already carry radical mutations.
In short, based on initial, theoretical/bioinformatical evaluation of the mutations in the spike protein of
Danish mink-derived viruses as outlined above, the following can be concluded:
 These mutations do not seem highly likely to raise new issues for vaccine development which
do not already exist, due to the well-known and relatively well understood currently ongoing
mutation and evolution of SARS-CoV-2 in humans.
 The spike protein mutations are evaluated as not being likely to have substantial impact the
efficacy of first-generation vaccines.
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2
In a preliminary experiment, SSI compared the neutralizing activity of 9 human convalescent sera
against a mink-derived SARS-CoV-2 isolate containing 4 simultaneous changes in the spike protein
(Δ69-70, Y453F, I692V and M1229I) with the neutralizing activity of the same sera against a control
SARS-CoV-2 strain without these spike mutations, using a monkey kidney cell line (Vero cells).
On average, these 9 human sera exhibited 2,6-fold reduction in neutralizing activity against the mink-
derived SARS-CoV-2 strain containing 4 simultaneous changes in the spike protein, compared to the
control virus without these changes. As a rule of thumb, in this type of assay, a 2.6-fold difference would
typically be considered to have, at best, low biological significance due to the analytical method varia-
bility/inaccuracy, and certainly require a large number of replicates and additional controls to document
with acceptable confidence.
Thus, while the serum neutralization data is preliminary and requires follow up (see detailing of data
strength/weakness and recommendation for follow-up work in main text), the SSI data nevertheless
suggests that the mutations observed in the spike protein of mink-derived viruses are unlikely to mark-
edly impact vaccine efficacy. This DKMA conclusion based on the SSI neutralization data is in agree-
ment with the theoretical/bioinformatic evaluation of the mutations in the spike protein of Danish mink-
derived viruses outlined above.
In short, for the reasons above, and with reservations for the preliminary nature of the available data,
the following can be concluded :
 The spike protein mutations seen in Danish mink-derived SARS-CoV-2 isolates are evaluated
as not being likely to have substantial impact the efficacy of first-generation vaccines and mon-
oclonal antibody therapeutics.
 Specifically, at the population level, the likelihood of spike protein mutations seen in mink-de-
rived SARS-CoV-2 isolates causing vaccine failure is considered to be very low (with the reser-
vation for the preliminary nature of currently available data mentioned below).
 However, it cannot be ruled out that vaccine failure may occur in individual vaccinees infected
with such isolates, particularly vaccinees mounting low neutralizing antibody responses to start
with.
 This is a preliminary risk assessment, based on available data; further laboratory analyses and
scientific studies are needed to better understand the impact of the changes in the spike protein
of mink-derived viruses for the transmissibility and neutralization of such viruses in human hosts.
Mechanisms behind and biological consequences of mutations
in spike protein of mink-derived viruses:
Danish mink-derived SARS-CoV-2 isolates have been reported to contain a number of mutations in
the spike protein, with some isolates containing 4 simultaneous mutations (Δ69-70, Y453F, I692V,
M1229I; ref 16).
Some of these mutations have been described as being mink-specific, i.e., as having originated in
mink (for example Y453F; ref 13 and 16).
However, data from GISAID, the COVID-19 viral genome analysis pipeline at Los Alamos as well as
scientific publications (14, 15) shows that the Y453F and M1229I were and are already present in
SARS-CoV-2 viruses circulating in humans, and as regards the Δ69-70 and I692V, viruses already cir-
culating in humans have comparable changes (e.g. I692F mutation and a variety of radical mutations
at spike positions H69 and V70 in human-derived viruses)(table 1). It should also be mentioned that
combinations of 2 mutations have already occurred in the spike protein of human-derived viruses, of-
ten including the D614G mutation which confers higher transmissibility between humans (8).
 By human-derived viruses is meant SARS-CoV-2 isolates from cases of human-human virus
transmission, unrelated to the mink outbreaks in the Netherlands and Denmark in march and
august 2020, respectively (6, 13, 16, 18).
 it is recognized that such so-called human-derived viruses very recently crossed into humans
from an animal reservoir, likely bats.
3
Mink were likely infected from humans, and represent naïve and susceptible hosts, with virus spread
between mink farms having been rapid. For all these reasons, the mutations in the spike protein of
mink-derived viruses are unlikely to represent the result of selective pressure from the immune re-
sponses in mink.
More likely, for the reasons above, the mutations seen in the spike protein of mink-derived viruses
were caused by the following 2 non-exclusive mechanisms:
 Founder effects: Mutations in the spike protein of human viruses were carried over into mink.
o This is in fact supported by the available data: The D614G mutation which confers
higher transmissibility of virus between humans arose in human-derived virus in China
and perhaps Germany around February 2020, and within 3 months outcompeted the
original D614 became the dominant virus form globally. The global spread of the
D614G mutant through the period February-May 2020 coincided temporally with the
disease outbreaks in mink in the Netherlands and Denmark (March and August 2020,
respectively; ref 6, 13, 18). This appears to be mirrored in an increased frequency of
the D614G mutant in mink-derived virus in Denmark compared to the Netherlands (ta-
ble 1).
 Adaption to a new host: Mink as well as ferrets are known to be susceptible to SARS-CoV-2
infection, but less so than humans (1, 6, 7). Thus, it is expected that some adaptive changes
may occur in the spike protein and other viral proteins after transmission from humans to
mink.
o In human-derived viruses, most mutations in the spike protein, particularly in the re-
ceptor-binding part of the protein, reduce the binding to human ACE2 receptor and/or
reduce spike protein stability, i.e., have negative effects on virus fitness and transmis-
sibility between humans (8, 9). Further, multiple mutations in spike have a more se-
vere negative effect on ACE2 binding and/or spike stability than single mutations (9).
o Finally, some mutations in the spike protein increase the binding to the human ACE2
receptor, and viruses carrying these mutations are already circulating between hu-
mans; yet, the frequency of such ACE2-binding-enhancing mutations in naturally cir-
culating viruses is very low (<0.3%) and has remained stable over time, most likely
because the SARS-CoV-2 virus already has the biologically maximally desirable bind-
ing to human ACE2 receptor, acquired already or soon after the species jump to hu-
mans, i.e. at the start of the pandemic (8, 9).
o This is not surprising, given that the binding affinity between the spike protein of
SARS-CoV-2 and human ACE2 is in the low pico-molar range (already very strong
binding to human ACE2, 10-fold stronger than for SARS-Cov-1; ref 9), and in experi-
ments intentionally selecting S protein mutants for increased binding to human ACE2,
this already high binding affinity could be only minimally improved (< 10-fold improve-
ments in binding affinity; ref 9).
o Thus, for the reasons above, adaptive changes are expected to increase virus fitness
in mink, but are likely to be detrimental to virus fitness in humans.
In short:
 It does not appear that SARS-CoV-2 spike protein has acquired unique mutations in mink.
 For this reason, the spike protein mutations observed in mink-derived viruses should not be
termed mink-specific.
 Thus, the spike protein mutations observed in mink-derived viruses do not appear to raise
new issues for vaccine and monoclonal antibody development which do not already exist due
to the well-known and relatively well understood currently ongoing mutation and evolution of
SARS-CoV-2 in humans (see for example refs 3, 8, 9, 10, 11, 14, 15, 17).
Only 2 of the mutations in the mink-derived viruses occur at spike protein sites targeted by neutralizing
antibodies (table 1):
 The receptor-binding site of the spike protein harboring the Y453F mutant is the most critical
of these, as it is able to induce particularly potent neutralizing antibody responses (9).
4
o However, the Y453F mutation is conservative, and not expected to have major impact
on receptor or antibody binding.
o In agreement with this, the Y453F spike mutation having been shown to have mild
positive effect on binding of the spike protein to the human ACE2 receptor (1,8-fold
increase in binding, likely within experimental error; ref 9).
 The N-terminal domain of the spike protein is known to also be the target for neutralizing anti-
bodies, and the deletions of amino acids 69 and 70 in mink-derived viruses may impact anti-
body binding.
o However, residues 69 and 70 in human-derived viruses already carry radical muta-
tions (table 1).
In short:
 The several mutations observed in the spike protein mink-derived viruses are already present
in human-derived viruses circulating between humans.
 For this reason, and the reasons detailed in the text above, the mutations observed in the
spike protein of mink-derived viruses are evaluated as not being likely to have substantial im-
pact the efficacy of first-generation vaccines and monoclonal antibody therapeutics.
 This assessment is based on available data, which is limited.
 Thus, unquestionably, studies are warranted and required to better understand the properties
and pathogenicity of mink derived viruses, as well as the implications of the changes present
in the spike protein of mink-derived viruses for SARS-CoV-2 serodiagnostics, monoclonal anti-
body therapeutics and vaccines in development.
Table 1: Summary of aminoacid mutations in spike protein of mink-derived SARS-CoV-2 in
Denmark and the Netherlands, based on publicly available data
Mutation in
spike protein
of mink-de-
rived virus,
compared to
human-derived
virus
Frequency
of mutation
Location of mutation
in spike protein
Spike mutation
already present
in human-de-
rived viruses ?
Comments
Δ69-70 (dele-
tion of aminoac-
ids 69 and 70)
* Not known N-terminal domain. H69D, H69Q,
H69R, H69Y,
V70A, V70F and
V70I mutations
present in hu-
man-derived vi-
ruses (rare,
<0.3%).
N-terminal domain is sur-
face-exposed, and
known to be target for
neutralizing antibodies in
humans.
Y453F 5/13 NL se-
quences.
8/12 DK se-
quences.
Receptor-binding do-
main.
Yes (rare,
<0.3%).
Receptor-binding domain
is surface-exposed. Most
of the known highly po-
tent neutralizing antibod-
ies target the receptor-
binding domain.
The Y453F mutation is
conservative, and not ex-
pected to have major im-
pact on receptor or anti-
body binding.
This is in agreement with
the Y453F spike muta-
tion having been shown
5
Mutation in
spike protein
of mink-de-
rived virus,
compared to
human-derived
virus
Frequency
of mutation
Location of mutation
in spike protein
Spike mutation
already present
in human-de-
rived viruses ?
Comments
to have mild positive ef-
fect on binding of the
spike protein to the hu-
man ACE2 receptor (1,8-
fold increase in binding,
likely within experimental
error; ref 9).
D614G 7/13 NL se-
quences.
12/12 DK
sequences.
D-domain of S1 subunit
(carboxy-terminal part of
S1 subunit)
Yes (currently
dominant in hu-
man epidemic,
globally).
Mutant considered to be
associated with higher
transmissibility between
humans, and higher sus-
ceptibility to neutraliza-
tion by antibodies.
The apparent increase in
frequency of the mutant
in Danish samples mir-
rors its increased domi-
nance in human-derived
viruses through the pe-
riod when the mink out-
breaks occurred in the
Netherlands and Den-
mark (march through au-
gust 2020; see ref. 17
and references therein).
I692V * Not known Seven aminoacids
downstream from furin
cleavage site between
S1 and S2 subunits (i.e.
in N-terminus of S2 sub-
unit).
I692 F mutation
in human-de-
rived viruses
(rare, <0.3%).
Spike protein location
not surface-exposed, un-
likely to be target for
neutralizing antibodies.
Mink mutation is more
conservative than mutant
already present in hu-
mans.
M1229I * Not known Transmembrane part Yes (rare,
<0.3%).
In addition,
M1229L and
M1229/ muta-
tions are also
seen in humans
(also rare,
<0.3%).
Spike protein location
not surface-exposed ,
unlikely to be relevant for
antibody neutralization of
virus.
The data in the table is based on publicly available spike protein sequences and information from SSI
(16).
Information regarding whether spike protein mutations in mink-derived viruses are already present in
human-derived viruses is from GISAID, the COVID-19 viral genome analysis pipeline at Los Alamos,
and scientific publications (14, 15).
Mutations are reported in single-letter aminoacid code, using the following convention: Residue in
SARS-CoV-2, Wuhan-Hu-1, followed by residue number in the spike protein, followed by residue in
mutates spike protein.
6
Accession numbers:
 Reference spike protein sequence, human-derived SARS-CoV-2, Wuhan-Hu-1 (first whole-genome SARS-CoV-2
sequence): Accession number YP 009724390.
 Mink-derived spike protein sequences from the Netherlands: Accession numbers QJS39496, QJS39507, QJS39519, QJS39531,
QJS39543, QJS39555, QJS39567, QJS39579, QJS39591, QJS39603, QJS39615, QJS39627, and QJF11995 (13 in total).
 Mink-derived spike protein sequences from Denmark: QNJ45106, QNJ45118, QNJ45130, QNJ45142, QNJ45154, QNJ45166,
QNJ45178, QNJ45190, QNJ45202, QNJ45214, QNJ45226 and QNJ45238 (12 in total).
* These mutations do not appear in the publicly available sequences.
Initial experimental work done at SSI to evaluate the implica-
tions of spike protein mutations in mink-derived viruses for
countermeasure development:
The data discussed in the following is from the first serum neutralization experiment of mink-derived
virus with human convalescent sera, carried out by Dr Anders Fomsgaard and Maria Magdalena Las-
sauniére (SSI report dated 02.11.2020; ref 16).
The neutralizing activity of human convalescent sera against a mink-derived SARS-CoV-2 isolate con-
taining 4 simultaneous changes in the spike protein (Δ69-70, Y453F, I692V and M1229I; see table 1)
was compared to the neutralizing activity of the sera against a control SARS-CoV-2 strain without
these spike mutations. Serial dilutions of convalescent sera were pre-incubated with fixed amounts of
mink-derived or control virus for 1h, followed by inoculation on Vero cells (African green monkey kid-
ney cell line) and incubation for 24h. Neutralization titers were defined as serum dilutions causing 50%
reduction in the levels of nucleocapsid protein production (NT50 values), determined by immunostain-
ing of fixed cells (exact experimental and analysis details lacking).
A total of 9 human convalescent sera were tested, all from patients early in the Danish epidemic.
In the following, all interpretations of the SSI data represent evaluation done at the DKMA.
The NT50 titers of the 9 human convalescent sera against the control SARS-CoV-2 strain ranged from
39 to >1280 (table 2). Four of these sera had neutralization titers < 80, considered to be low titers, and
for the group as a whole, the geometric mean titer was 168 (table 1). This wide range of neutralization
titers as well as relatively high frequency of low-end NT50 values has been reported by others for SARS-
CoV-2 convalescent sera, and was as such not surprising (2, 4, 5). However, with the reservation that
neutralization assays are not standardized and neutralization titer values difficult to compare between
datasets, these patient sera appeared to exhibit lower neutralization titers than expected in vaccinees.
For the mink-derived strain, neutralization titers ranged from 5 to >1280, with a geometric mean of 64
(table 2).
Thus, on average, these 9 human sera exhibited a 168/64=2.6-fold reduction in neutralizing activity
against the mink-derived SARS-CoV-2 strain containing 4 simultaneous changes in the spike protein,
compared to the control virus without these changes.
Neutralizing titers against control virus exhibited a good linear correlation with neutralization titers
against mink-derived virus (figure 1, R2>0,9), with inclinations of the regression lines were 0,74 to 0,97
(figure 2).
Based on the regression equations shown in figure 2, a neutralization titer of for example 160 against
human-derived virus corresponds to a neutralization titer of 0.75 x 160 - 41 = 79 (figure 2 panel A) to
0.98 x 160 - 76 = 80 (figure 2 panel B) against mink-derived virus.
Thus, based on regression analysis, human sera exhibited 160/80 = 2-fold to 160/79 = 2-fold reduction
in neutralizing activity against the mink-derived SARS-CoV-2 strain containing 4 simultaneous changes
in the spike protein, compared to the control virus without these changes, in agreement with the results
based on simple geometric group means detailed above.
Neutralization assays are known to exhibit a relatively high level of variability, and as a simplified, gen-
eral rule of thumb, differences in neutralization titers of 10-fold or more are considered to be high and
likely biologically significant (see for example ref. 3 and 8), whereas the biological significance of neu-
tralization titer differences of less than 10-fold are less likely to have biological significance, and differ-
ences of 2 fold or less would typically be considered to have at best low biological significance, and
7
certainly require a large number of replicates and additional controls to document with acceptable con-
fidence (8).
Thus, the observed reduction in mean neutralization activity of human convalescent sera against mink-
derived virus (average 2,6-fold reduction for group of 9 convalescent sera) is considered to be of low
significance, given the known variability of neutralization assays, and preliminary nature of the data
(see section on data strength and recommendations for follow-up experiments below).
Sera which were low-titered against the control virus exhibited the largest reductions in titer against the
mink-derived virus, and this correlation was significant (figure 1; P=0,0182). Thus, the potential risk of
failure of COVID-19 vaccines against mink-derived cluster 5 strains is likely highest in vaccinees exhib-
iting low vaccine responses to start with.
At the same time, of the 4 sera with titers <80 (sera 1 through 4, table 2), neutralization of mink virus
varied from 7% to 72% of the neutralization of control virus (table 2), and in this (admittedly very small)
sub-group of sera with low neutralization titers, the correlation between neutralization of human and
mink virus was less clear (figures 1 and 2; not detailed). This is not surprising, because the distribution
of circulating polyclonal neutralizing antibodies in patients against different parts of the S protein (for
example balance between amounts of circulating polyclonal neutralizing antibodies against N-terminal
domain versus receptor-binding domain) is known to be idiosyncratic amongst patients (3, 4, 5), and
also, affinities of neutralizing polyclonal anti-S protein antibodies differ between patients (4); these idio-
cyncrasies in circulating polyclonal neutralizing antibody responses are likely due to factors such as
subtle differences in how the spike protein was presented to patient B-cells, age of patients, MHC-II
haplotype of patients, etc.
In short:
 The serum neutralization data is preliminary and has several shortcomings requiring follow up
(see detailing and recommendation for follow-up work above).
 Nevertheless, the data suggests that the mutations observed in the spike protein of mink-de-
rived viruses are unlikely to impact vaccine efficacy.
 This conclusion based on evaluation of SSI data is in agreement with the conclusion drawn
based on bioinformatic analysis and theoretical considerations in the section above, titled
"Mechanisms behind and biological consequences of mutations in spike protein of mink-derived
viruses".
Table 2: Raw serum neutralization data.
Patient Neutralization titer (NT50) Titer ratio
mink virus/control virus
Control virus iso-
late
Mink-derived cluster 5 virus
isolate
1 39 28 0,72
2 68 5 0,07
3 54 9 0,17
4 67 30 0,45
5 186 67 0,36
6 >1280 >1280 1,00
7 846 606 0,72
8 186 54 0,29
9 291 177 0,61
* Descriptive statistics, all 9 sera:
mean: 335 251 0,49
median: 186 54 0,45
geometric
mean:
168 64 0,38
Descriptive statistics, excl. patient 6:
mean: 217 122 0,42
median: 127 42 0,40
8
geometric
mean:
142 52 0,36
The data is from the first neutralization experiment, carried out by Dr Anders Fomsgaard and Maria
Magdalena Lassauniére (SSI report dated 02.11.2020; ref 16).
* The patient 6 serum with a titer of >1280 was assigned the value 1280.
The geometric mean is usually used in evaluating results from serological assays such as this; for con-
venience, mean, median and geometric mean values are all shown.
Figure 1: Relationship between magnitude of anti-SARS-CoV-2 antibody response in patients
against homologous (human-derived) virus, and failure to neutralize mink-derived virus
The inclination of the regression line was significantly different from 0 (P=0,182; GraphPad QuickCalc software,
available online https://www.graphpad.com/quickcalcs/linear2/)
9
Figure 2: Ability of convalescent human sera to neutralize mink-derived SARS-CoV-2 cluster 5
isolate with 4 simultaneous changes in spike (Δ69-70, Y453F, I692V, M1229I)
Panel A, serum with a titer of >1280 is excluded.
Panel B, serum with a titer value of >1280 is included, and assigned a titer value of 1280.
Strength of data from initial studies, and recommendations for
follow-up experiments:
All interpretations of the SSI data below represent evaluation done at the DKMA.
The data has the following shortcomings:
 The cell culture system used for neutralization assays is permissive for SARS-CoV-2 replication
(6), but is non-human, and represents a cell type which is not a primary target for infection in
humans (Vero cells; African green monkey kidney cell line). The ACE2 receptor expressed by
Vero cells has been reported to differ by approx. 5% from human ACE2 protein at the amino
acid level (1), and while Vero cells are often used for in vitro studies of SARS-CoV-2 virus,
typically human cell lines are also included (6), and results obtained using Vero cells and human
cells may differ (6).
 For neutralization results to be valid, identical amounts of mink-derived and control virus should
be used, and these 2 viruses should exhibit identical or very comparable replication kinetics in
Vero cells. It is stated in the SSI report that same amounts of mink-derived and control virus
10
were used, but it is not known which methods were used to quantitate these 2 virus isolates.
Comparison of replication kinetics in Vero cells for the 2 viruses is not provided.
 With the reservation that neutralization assays are not standardized and neutralization titer val-
ues are difficult to compare between datasets, the patient serum panel appeared to be low
titered compared to expected neutralization titers in vaccinees.
 The serum neutralization data represents a single experiment, the number of replicate determi-
nations is not reported, and the overall variability of the neutralization assay is not known; such
assays are known to be quite variable.
 The technical performance of the neutralization assay is not known; specifically, the cutoff level
between positive and negative sera, and the linearity (dose-response) of the assay are of inter-
est.
For the reasons above, the strength of the data is evaluated as low (preliminary results), as is also
acknowledged in the SSI report.
For initial confirmatory follow-up experiments, the following is recommended:
 Clinical data should be provided for patient sera (e.g. patient age, and time interval since infec-
tion).
 Sera which are more representative of vaccinees should be included.
 More virus strains should be included.
 More technical information should be provided for the variability of the neutralization assay,
controls used, and the performance of the assay (see above).
 The virus neutralization/serology work should be expanded to include determination of the af-
finity of the mutated spike protein in mink-derived cluster 5 strain(s) for human ACE2 receptor.
It should also be mentioned here that even the relatively modest and focused follow-up work outlined
above represents a relatively large effort.
11
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7917.ES.2020.25.23.2001005


Dato 10. november 2020
Sagsnr. 2020110983
Lægemiddelstyrelsens syn på betydningen af Statens Serums Instituts risikovurdering af mink-
deriveret virus, og mulige betydning for Covid-19 vacciner under udvikling.
Lægemiddelstyrelsen er blevet anmodet af Sundheds-og Ældreministeriets departement om en vurde-
ring af Statens Serums Instituts udmelding angående mink-deriveret Covid-19 virus, og om disse
mink-deriverede virus har nogen betydning for de Covid-19 vacciner, som EU-kommissionen er i færd
med at indkøbe til blandt andre den danske befolkning.
Dertil spørger Sundheds- og Ældreministeriets departement tillige, om der er en større risiko for lavere
effekt forbundet med nogle vacciner frem for andre som følge af disse virusmutationer.
Baggrund
SSI har den 3. november 2020 udarbejdet en risikovurdering, hvori de konkluderer, at ”en fortsat mink-
avl under en igangværende Covid-19 epidemi indebærer en betydelig risiko for folkesundheden, her-
under for mulighederne for at forebygge Covid-19 med vacciner”.
Lægemiddelstyrelsen har efterfølgende modtaget risikovurderingen samt forsøgsdata fra SSI i relation
til det eksperiment med antistoffer, som der henvises til i risikovurderingen. Lægemiddelstyrelsens
vurdering vil således i det følgende basere sig på både risikovurdering, de tilgængelige forsøgsdata
samt nuværende tilgængelig viden om Covid-19 vaccine udvikling.
Vurdering
Lægemiddelstyrelsen lægger i sin vurdering vægt på at tilgængelige data, både i forhold til antistoffers
effekt på mink-deriveret Covid-19 virus samt de Covid-19 vacciner som er under udvikling, er meget
begrænsede på nuværende tidspunkt. Lægemiddelstyrelsens vurdering er derfor underlagt store for-
behold for de manglende data.
Lægemiddelstyrelsen antager, at alle de Covid-19 vacciner, der er under udvikling, er rettet mod den
oprindeligt isolerede Wuhan SARS-CoV-2 stamme. For at få mere viden om de forskellige Covid-19
vacciner kan have forskellig effekt mod mink-deriveret virus, er Lægemiddelstyrelsen i proces med at
indhente uddybende teknisk information om vaccinernes sammensætning og lægemiddelproducenter-
nes vurdering af risiko for nedsat effekt af vaccinerne som følge af de navngivne mutationer. Informati-
onen indhentes via EU Kommissionen fra de relevante lægemiddelproducenter, og Lægemiddelstyrel-
sen kan ikke på nuværende tidspunkt sige hvornår informationen forventes at foreligge.
Af informationen fra SSI1 fremgår det, at effekten af humane antistoffer mod mink-deriveret virus er
lavere end effekten mod den oprindelige human-deriverede virus. Lægemiddelstyrelsen noterer sig
dog, at niveauet af antistoffer anvendt i forsøget generelt er lavere, end hvad der er forventet i vacci-
nerede personer, og at den nedsatte effekt imod mink-deriveret virus er af en beskeden størrelsesor-
den.
Lægemiddelstyrelsen vurderer derfor, at de højere antistof-niveauer som vacciner mod human Covid-
19 forventes at fremkalde, med stor sandsynlighed også vil beskytte helt eller delvist mod mink-derive-
ret Covid-19. På baggrund af nuværende viden vurderer Lægemiddelstyrelsen, at det ikke kan udeluk-
kes, at vaccinernes effekt er lavere over for mink-deriveret Covid-19 virus end human Covid-19 virus,
om end nuværende viden tyder på at risikoen herfor er meget lav.
Det kræver dog flere data, før en præcis vurdering af vaccineeffekten kan udledes. Når disse data kom-
mer i Lægemiddelstyrelsens besiddelse, vil det være muligt at uddybe mink-deriveret Covid-19 betyd-
ning for de kommende Covid-19 vacciner. Det skal afslutningsvis bemærkes, at grundet det meget store
omfang af det eksperimentelle arbejde forventes det ikke at dette spørgsmål kan blive endeligt afklaret
inden vaccinerne skal igennem godkendelsesproceduren i EMA.
1
SSI har i sin risikovurdering nævnt at data fra det indledende eksperiment bør bekræftes i et gentaget eksperiment
Sundheds- og Ældreudvalget 2020-21
SUU Alm.del - Bilag 105
Offentligt
Miljø- og Fødevareudvalget 2020-21
L 77 endeligt svar på spørgsmål 186
Offentligt


Folketingets Miljø- og Fødevareudvalg har den 8. december 2020 stillet følgende
spørgsmål nr. 186 til L 77 (Forslag til lov om aflivning af og midlertidig forbud mod
hold af mink) til sundheds- og ældreministeren, som hermed besvares. Spørgsmålet
er stillet efter ønske fra Per Larsen (KF) og Egil Hulgaard (KF).
Spørgsmål nr. 186:
”I risikovurderingen fra SSI slås der tvivl om fremtidige vacciners effekt som følge af
minkvarianter af coronasmitte. Vil ministeren redegøre for, om der er andre sund-
hedsfaglige kilder, der har udtrykt samme bekymring og slået tvivl om en fremtidig
vaccines effekt? Og vil ministeren i så tilfælde oversende doku e tatio for SSI’s
konklusioner fra eksterne eksperter?”
Svar:
Jeg kan hertil oplyse, at EU-agenturet for sygdomsforebyggelse (ECDC) i en rapport af
12. november 2020 om ECDCs risikovurdering af ny SARS-CoV-2 variant fundet i mink
har anført, at
”O e of the clusters (Cluster 5), which was reported as circulating in August and Sep-
tember 2020, is related to a variant with four genetic changes, three substitutions and
one deletion, in the spike (S) protein. Since the S protein contains the receptor-binding
domain, and is a major target for immune response, such mutations could, in theory,
have implications for viral fitness (ability to infect humans and animals), transmissibil-
ity, and antigenicity. As a consequence, the evolution of viruses with increasing
changes in functional domains of the S protein could affect treatment, certain diag-
nostic tests and virus antigenicity. It could also have an impact on the effectiveness of
developed vaccine candidates, and possibly require them to be updated. Investiga-
tions a d studies are o goi g to larif the e te t of these possi le i pli atio s.”
Jeg kan videre oplyse, at WHO i deres notat om mink-situationen i Danmark af 6. no-
vember 2020 bl.a. vurderer, at fundene i Danmark har global relevans, og understre-
ger derfor vigtigheden af at dele epidemiologisk, virologisk og genom-sekvenserings-
information med andre lande. Herudover råder WHO alle lande til at øge overvågnin-
gen af smitte mellem dyr og mennesker samt styrke biosikkerheden for at mindske
denne form for smitte.
Endelig vil jeg henvise til SUU alm. del - Bilag 105.
Med venlig hilsen
Magnus Heunicke / Michelle Aagaard
Folketingets Sundheds- og Ældreudvalg
Holbergsgade 6
DK-1057 København K
T +45 7226 9000
F +45 7226 9001
M sum@sum.dk
W sum.dk
Dato: 09-12-2020
Enhed: MEDINT
Sagsbeh.: DEPMIAA
Sagsnr.: 2016251
Dok. nr.: 1507287
. / .
Miljø- og Fødevareudvalget 2020-21
L 77 endeligt svar på spørgsmål 186
Offentligt


Til Folketingets Sundheds- og Ældreudvalg
Til orientering vedhæftes Lægemiddelstyrelsens vurdering vedr. vacciner indkøbt via
EU og virusmutationer fra mink.
Med venlig hilsen
Magnus Heunicke
Folketingets Sundheds- og Ældreudvalg
Sundheds- og ældreministeren
Holbergsgade 6
DK-1057 København K
T +45 7226 9000
F +45 7226 9001
M sum@sum.dk
W sum.dk
Dato: 17-11-2020
Enhed: BESS
Sagsbeh.: DEPBIWI
Sagsnr.: 2016022
Dok. nr.: 1468089
. / .
Sundheds- og Ældreudvalget 2020-21
SUU Alm.del - Bilag 105
Offentligt
Miljø- og Fødevareudvalget 2020-21
L 77 endeligt svar på spørgsmål 186
Offentligt