Case report on a defective antibody response against pneumococcal serotype 9V in a patient with a single episode of pneumonia
Kessel et al. Pneumonia
Case report on a defective antibody response against pneumococcal serotype 9V in a patient with a single episode of pneumonia
Diana van Kessel 2 3
Thijs Hoffman 3
Heleen van Velzen-Blad 0
Bob Meek 0
Suzan van Mens 0
Jan Grutters 2 3
Ger Rijkers 0 1 4
0 Laboratory of Medical Microbiology and Immunology, St. Antonius Hospital , Koekoekslaan 1, 3435, CM, Nieuwegein , The Netherlands
1 Department of Science, University College Roosevelt , Lange Noordstraat 1, 4330, AB, Middelburg , The Netherlands
2 Division of Heart and Lungs, University Medical Center , Heidelberglaan 100, 3584, CX, Utrecht , The Netherlands
3 Department of Pulmonology and Respiratory Medicine, St. Antonius Hospital , Koekoekslaan 1, 3435, CM, Nieuwegein , The Netherlands
4 Department of Pharmaceutical Sciences, Utrecht University , Utrecht , The Netherlands
Background: Patients with recurrent respiratory tract infections and an impaired response to pneumococcal polysaccharide vaccination are diagnosed with a specific antibody deficiency. In adult patients with pneumococcal pneumonia an impaired antibody response to the infecting pneumococcal serotype can sometimes be found. It is unknown whether these patients are unable to produce an adequate anti-polysaccharide antibody response to pneumococcal vaccination after recovery. Case presentation: The authors describe a case of invasive pneumonia caused by Streptococcus pneumoniae serotype 9V in a previously healthy 35-year-old female. This patient did not produce serotype-specific antibodies against the infecting serotype during disease. After pneumococcal polysaccharide vaccination 3 months after recovery, she responded adequately to most other pneumococcal serotypes, but still had no response to the infecting serotype 9V. However, after 9 years (and prior to pneumococcal-conjugate vaccination) normal antibody levels against 9V were found. These antibody levels further increased after pneumococcal-conjugate vaccination. Conclusion: The authors believe that this case is the first description of a temporary deficient response to the infecting pneumococcal serotype in adults, while other reports with similar observations all involved children.
Community-acquired pneumonia; Streptococcus Pneumoniae; Antibody deficiency; Vaccination; Polysaccharide vaccine
Community-acquired pneumonia (CAP) is a serious
disease, most frequently caused by Streptococcus pneumonia
]. Invasive and non-invasive pneumococcal disease has a
high mortality risk, especially in the elderly patient with
]. Vaccination with a 23-valent
pneumococcal polysaccharide vaccine (23vPPV) induces antibody
production against the external polysaccharide capsule of the
]. An impaired response to pneumococcal
polysaccharide vaccination can be a risk factor for recurrent
respiratory tract infections [
]. Vaccination with 23vPPV is
part of the immunological screening in patients with
recurrent respiratory tract infections [
]. Those patients with an
impaired response to pneumococcal polysaccharides are
diagnosed with a specific antibody deficiency [
Previously it was shown that a substantial proportion of
patients with pneumococcal pneumonia did not show an
antibody response to the infecting pneumococcal serotype,
either during the clinical course of the disease or during
]. This raises the question whether
these patients are able to mount a serotype-specific
antibody response after vaccination with 23vPPV.
This case report describes a patient with
pneumococcal pneumonia in whom the infecting serotype was
identified. After recovery, an assessment of the humoral
immune status was made, including analysis of the
antibody response to pneumococcal polysaccharide
A 35-year-old female was seen at the emergency
department of St. Antonius Hospital, Koekoekslaan, The
Netherlands. She presented with fever up to 40 degrees
Celsius, shaking chills, dry cough, nausea, headache and
right-sided chest pain. These symptoms were present for
1 week. The patient’s medical history was unremarkable;
she didn’t use any medication and was a non-smoker.
The diagnosis of pneumonia was made by physical and
laboratory examination. The chest radiography showed a
large right-sided lobar infiltrate (Fig. 1).
Because of impending respiratory insufficiency and
hypotension, the patient was admitted to the intensive
care unit and immediately intubated. Treatment with
penicillin and erythromycin was started.
Streptococcus pneumoniae was detected as the
causative microorganism by a blood and sputum culture and
positive urine antigen testing, and identified as serotype
9V. A pharyngeal swab showed no signs of respiratory
viruses on PCR testing. Antibiotic treatment was
converted to penicillin only.
Following 9 days of mechanical ventilation, she was
transferred to the ward where she made a good recovery
and was discharged after 16 days.
Antibody titers against the capsular polysaccharides of
14 pneumococcal serotypes were measured on a
multiplex immunoassay (Luminex 200, Luminex Corporation,
Austin, Texas, United States [US]) as previously
described (serotypes 1, 3, 4, 6B, 7F, 8, 9 N, 9V, 12F, 14,
18C, 19A, 19F, and, 23F; Danish nomenclature) [
Samples were taken at the day of admission and 42 days
later. In the recovery sample the patient showed a low
antibody titer and no titer rise against pneumococcal
serotype 9V. She had not been vaccinated with a
pneumococcal vaccine in the past.
Three months after admission to the hospital, the
patient was seen at the outpatient department for a
work-up according to the diagnostic protocol
developed by the European Society for Immunodeficiency
]. In that context, 23vPPV was administered.
Pneumococcal polysaccharide antibodies against 8
pneumococcal serotypes were measured on a Luminex
platform before vaccination and 4 weeks after
vaccination (serotypes 3, 4, 6B, 9V, 14, 18C, 19F, and 23F;
Danish nomenclature). The results showed that the
patient had a sufficient antibody response to 5 of the
8 pneumococcal serotypes tested (Table 1), but no
response whatsoever against her infecting serotype 9V.
The patient therefore did not have an adequate
antibody response specifically to pneumococcal serotype
9V either after natural exposition or after vaccination
with 23vPPV. Immunological work up showed no
other abnormalities; i.e. serum immunoglobulins,
IgGsubclasses and complement were all normal (Table 2).
The patient has had no severe or recurrent infections
during the 9 years that have followed this first
episode of pneumonia.
Recently the patient was included in the so-called
CAPolista study (patient #6) [
]. In this study, patients
who have experienced an episode of
communityacquired pneumonia were vaccinated with 13-valent
pneumococcal conjugate vaccine and antibodies were
measured before and after vaccination. Antibodies were
measured on a Luminex platform as previously
described (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C,
19A, 19F, 23F; Danish nomenclature) [
unexpectedly, a high anti-9V titer of 4 μg IgG/ml was
found in the pre (conjugate) vaccination serum, which
increased 3.8-fold after vaccination (Table 1). Also for
serotype 6B the antibody titers had increased
substantially in the 10 years after pneumococcal polysaccharide
A sufficient serotype-specific response is defined as having titers higher than 1.3 μg/ml and at least a two-fold increase between pre- and post-vaccination
Antibody levels to the infecting pneumococcal serotype (9V) are indicated in bold
vaccination. For serotype 4 the antibody levels were and
remained low (Table 1).
Discussion and conclusions
Immunological investigation in this case of severe
pneumonia in a previously healthy 35-year-old female showed
an absent pneumococcal antibody response to the infecting
serotype during the course of the disease. Upon vaccination
with the 23vPPV 3 months after recovery, 9V antibodies
remained low. Nine years later, a protective (i.e. >1.3 μg/ml)
level of 9V antibodies was found prior to revaccination with
the 13-valent conjugate vaccine, and this level increased
further after conjugate vaccination.
According to the 2015 AAAAI/ACAAI criteria [
patient has an impaired response to pneumococcal
capsular polysaccharides because she had an adequate
response to less than 70% of the tested serotypes (5 out of
8). In the authors’ opinion, however, this patient does not
meet the diagnostic criteria (inadequate response to
pneumococcal polysaccharide vaccination, in combination
with clinical characteristics suggestive of an
immunodeficiency, such as recurrent infections [
]), because she had
no recurrent respiratory tract infections before or after the
episode of the pneumococcal pneumonia.
The high antibody titer against 9V (and 6B for that
matter) 9 years after the invasive pneumonia caused by
serotype 9V and 23vPPV vaccination indicates a temporary
hyporesponsiveness to selective serotypes including the
infecting serotype that recovered and high antibody levels
were observed after 9 years that further increased upon
revaccination with the 13-valent conjugate vaccine. All
serotype specific antibody measurements were repeated
with essentially the same results (not shown). There are
no additional blood samples from the 9-year period; the
patient was in good clinical condition and didn’t report
back at the hospital. Therefore, it is unknown when the
9V antibodies increased or whether there was renewed
colonization or a subclinical infection with 9V during that
period. At any rate, there was a temporary defect in the
ability to respond to serotype 9V pneumococci. The
cellular and/or molecular causes of this temporary
hyporesponsiveness are unknown.
Serotype-specific hyporesponsiveness towards the
infecting serotype has been described in children [
children who had been vaccinated with PCV prior to
developing invasive pneumococcal disease, antibody
levels directly after the infection were lower against the
infecting serotype compared to other vaccine serotypes
]. Furthermore, it has been observed that some
children with invasive pneumococcal disease remained
hyporesponsive to the infecting pneumococcal serotype,
even after recovery [
]. A possible explanation for
this phenomenon is that hyporesponsiveness to PCV can
be caused by pneumococcal carriership at time of
vaccination. It has been shown that nasopharyngeal
colonization with a specific pneumococcal serotype at
the time of vaccination is associated with a lower
response to that serotype, even after subsequent booster
]. Another possible explanation is
that during the pneumococcal infection, a high load of
circulating polysaccharide antigens can cause a
temporary immune paralysis [
]. The above considerations
have been made based on observations in children, and
data in adults are lacking.
In this case, immune investigations were performed
because the patient participated in a study on
pneumococcal pneumonia in the authors’ center. This specific
immunological defect would normally not have been
found, as the patient did not meet the criteria for
immunological screening [
]. This case gives rise to the
debate whether all hospitalized patients with a first
episode of pneumococcal pneumonia should undergo an
immune status assessment, or at least pneumococcal
vaccination and measurement of antibodies to the most
common pneumococcal serotypes. The CAPolista study
has shown that the vast majority of CAP patients who
were vaccinated with a conjugated polysaccharide
vaccine do show an adequate antibody response [
In conclusion, these findings suggest that temporary
hyporesponsiveness towards the causative pneumococcal
serotype in CAP patients may occur, but does not
necessarily indicate a selective immunodeficiency because
recovery of the impairment occurred over time. It is
unknown whether the temporary impairment was the
cause of pneumonia or occurred due to a high load of
capsular polysaccharides because of this pneumonia.
However, this case report illustrates that pneumococcal
infections may be associated with temporary
hyporesponsiveness to infecting serotypes in adults as well as
We acknowledge Dr. G.J. Wagenvoort for sharing the data on the CAPolista
study and Mr. B. de Jong for his expert technical assistance.
No external funding was requested or used for this study.
Availability of data and materials
The datasets used and/or analyzed during the current study are available
from the corresponding author on reasonable request.
DvK analyzed and interpreted the patient data regarding the pulmonary
disease; HvV-B, BM, and GTR supervised the antibody measurements; TH was
a major contributor in writing the manuscript; all authors read and approved
the final manuscript.
Ethics approval and consent to participate
Approval was received from the local Ethical Committee for the study and
informed consent was obtained.
Consent for publication
The authors declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional affiliations.
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