Congenitally impaired pattern-recognition receptors in pathogenesis of pediatric invasive and recurrent pneumococcal infection

Here we review currently available data showing that innate immune signs predisposing to recurrent and invasive pneumococcal infections were identified in children. Streptococcus pneumoniae (pneumococcus) belongs to Grampositive bacteria being the major cause of morbidity and mortality in infants, especially in developing countries and in communities with low socioeconomic status. Due to the lack of anti-pneumococcal vaccination, the significant proportion of pneumococcus carriers develop non-invasive (pneumonia, otitis media, sinusitis) and severe invasive (bacteremia/septicemia, meningitis) pneumococcal infection. A great deal of diverse factors related to pneumococcus biological features (virulence factors) as well individualized host-specific immunity are implicated in efficient bacterial penetration across the mucous membranes. The TLR signaling system plays a crucial role in the human nonspecific defense upon the first encounter with the pathogen. Various TLRs comprise the first pattern recognition receptor fami ly ever described which sense ligands derived from the outer bacterial wall. The complement system is the ancient innate immunity component mainly involved in intravascular elimination of bacterial agents. In addition, the complement proteins serve as a bridge between innate and adaptive immunity, ensuring optimal conditions for B- and T-cell maturation and differentiation. Because pneumococcus secretes the IgA protease, a local protective effects related to IgA antibodies might not be so prominent. Therefore, B-cell immunodeficiency and impaired complement system hold a lead place among congenital causes resulting in severe and recurrent pneumococcal infections in children. Thus, based on available data, we concluded that impaired B-cell function, the complement components deficiency as well as receptor-recognition receptors (TLR-2, -9, -4, MYD88 adapter protein, TLR cascade enzymes: IRAK4, NEMO, NOD-like receptors: NOD2, NLRP3; C-type lectins: MBL, Dextin-2, and, possibly, ficoline) play the most important role among congenital immunodeficiencies predisposing to invasive and recurrent pneumococcal infections play the most important role among congenital immunodeficiencies predisposing to invasive and recurrent pneumococcal infections, and should be used as a rationale for immunological surveillance and organizing immunogenetics screening in these patients.

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Response to Immunizations Following Allogeneic HCT with Adjuvant Rituximab Therapy.

Blood ◽

10.1182/blood.v106.11.3242.3242 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3242-3242 ◽

Cited By ~ 1

Author(s):

Mary Pao ◽

Esperanza B. Papadopoulos ◽

Farid Boulad ◽

Hugo Castro-Malaspina ◽

Ann Jakubowski ◽

...

Keyword(s):

T Cell ◽

Hepatitis B ◽

B Cell ◽

Pneumococcal Vaccine ◽

Cell Function ◽

Pneumococcal Vaccination ◽

Hepatitis B Vaccination ◽

Allogeneic Hct ◽

Initial Series ◽

Adequate Response

Abstract Use of anti-CD20 monoclonal antibody after allogeneic HCT for the treatment EBV lymphoma or viremia, autoimmune cytopenias, and the prevention or treatment of recurrent NHL has become more frequent. There is limited data on the effect of this therapy on specific antibody production following allogeneic HCT. We therefore examined the response to standard childhood immunizations of 30 patients, including 20 adults (>18 years of age) who received rituximab following a T cell depleted (n=26) or unmodified (n=4) HCT at our institution. T cell function was assessed in vitro by proliferative response to PHA and B cell reconstitution was confirmed by recovery of CD19+ and CD20+ circulating lymphocytes. Patients received a median (range) of 4 (1–12) doses of rituximab, with 15 patients receiving 4–6 doses. The median age of the patient population was 28.5 years with a range of 0.8–63.0 years. Children (median age: 8.5 yrs) received a transplant from an unrelated (n=7), HLA mismatched related (n=2), or HLA matched related (n=1) donor and adults (median age: 42.5 yrs), received a transplant from an unrelated (n=7), HLA mismatched related (n=2), or HLA-matched related (n=11) donor. Patients were vaccinated when their PHA response was at least 75% of the lower limit of normal and CD20+ cells were >100/ul. Vaccination was initiated at a median of 270 and 525 days following the last dose of rituximab in children and adults, respectively. A two to 3-fold rise in titers following a series of 3 tetanus and IPV vaccinations occurred in 19 of 21 and 19 of 19 evaluable patients, respectively. Although 8 of 9 children responded to the H flu conjugate vaccine, only 5 of 13 adults mounted an adequate response. Eighteen patients received the recombinant Hepatitis B vaccine. Nine responded following the initial series (5/7 children, 4/11 adults). Two of three patients who failed initial Hepatitis B vaccination, responded to a second series (1 child, 1 adult). Response to pneumococcal vaccination was the least consistent. None of 11 adults who received the unconjugated 23-valent pneumococcal vaccine developed an adequate response. In view of this observation, children given rituximab were immunized with the conjugated pneumococcal vaccine. Four of eight children responded to the initial series, and two additional children responded following a second series. These preliminary data suggest that both adult and pediatric patients given rituximab following an allogeneic HCT can mount successful antibody responses to standard T-helper cell dependent vaccines. However, B cell responses to T cell independent vaccines may be particularly impaired. Larger prospective trials, stratified by age, comparing vaccine responses in patients following allogeneic transplant in the presence or absence of post transplant rituximab therapy are warranted.

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Immunization with a Combination of Three Pneumococcal Proteins Confers Additive and Broad Protection against Streptococcus pneumoniae Infections in Mice

Infection and Immunity ◽

10.1128/iai.00473-09 ◽

2009 ◽

Vol 78 (3) ◽

pp. 1276-1283 ◽

Cited By ~ 35

Author(s):

Kaifeng Wu ◽

Xuemei Zhang ◽

Jing Shi ◽

Nan Li ◽

Dairong Li ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Pneumococcal Infection ◽

Combination Vaccine ◽

Protective Effects ◽

Complete Protection ◽

Pneumococcal Infections ◽

Pneumococcal Strain ◽

Infection Models ◽

Caseinolytic Protease

ABSTRACT Pneumococcal polysaccharide-based vaccines are effective in preventing pneumococcus infection; however, some drawbacks preclude their widespread use in developing and undeveloped countries. Here, we evaluated the protective effects of ATP-dependent caseinolytic protease (ClpP), pneumolysin mutant (ΔA146 Ply), putative lipoate-protein ligase (Lpl), or combinations thereof against pneumococcal infections in mice. Vaccinated mice were intraperitoneally and/or intranasally challenged with different pneumococcal strains. In intraperitoneal challenge models with pneumococcal strain D39 (serotype 2), the most striking protection was obtained with the combination of the three antigens. Similarly, with the intranasal challenge models, (i) additive clearance of bacteria in lungs was observed for the combination of the three antigens and (ii) a combination vaccine conferred complete protection against intranasal infections of three of the four most common pneumococcal strains (serotypes 14, 19F, and 23F) and 80% protection for pneumococcal strain 6B. Even so, immunity to this combination could confer protection against pneumococcal infection with a mixture of four serotypes. Our results showed that the combination vaccine was as effective as the currently used vaccines (PCV7 and PPV23). These results indicate that system immunization with the combination of pneumococcal antigens could provide an additive and broad protection against Streptococcus pneumoniae in pneumonia and sepsis infection models.

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CLINICAL AND EPIDEMIOLOGICAL ASSESSMENT OF THE EFFECTIVENESS OF VACCINATION OF CHILDREN AGAINST PNEUMOCOCCAL INFECTION IN THE AMUR REGION

Journal of microbiology epidemiology immunobiology ◽

10.36233/0372-9311-2016-3-57-63 ◽

2016 ◽

pp. 57-63 ◽

Cited By ~ 1

Author(s):

A. G. Chuchalin ◽

G. G. Onischenko ◽

V. P. Kolosov ◽

O. P. Kurganova ◽

N. L. Tezikov ◽

...

Keyword(s):

Hospital Admissions ◽

Pneumococcal Infection ◽

Acute Otitis Media ◽

Total Duration ◽

Monitoring Program ◽

Pneumococcal Vaccination ◽

Community Acquired Pneumonia ◽

Amur Region ◽

Pneumococcal Infections ◽

High Level

Aim. To study the effectiveness of anti-pneumococcal vaccination of children in the organization of anti-epidemic measures in the areas of the flood in the Amur region. Material and methods. The monitoring program included 4988 children aged 2 to 5 years who have risk factors for pneumococcal infection. Pneumococcal conjugate vaccine Prevenar-13 was used for immunization. Data on the incidence of child with acute respiratory infection, acute otitis media, pneumonia, meningitis during the post-vaccination period were taken into account. To evaluate the effectiveness of vaccination we used indicators and specific criteria (coefficient prophylactic vaccination and infection index). Results. The level of total morbidity of children in post-immunization period decreased by 13.6%; the number of cases of pneumonia in the population of observed children decreased by 2.3 times; the total duration of the illness in children decreased by 14.6%, the number of courses of antibiotic therapy was reduced by 21.3%, the number of hospital admissions of children- 38.4%, the number of days of temporary disability of parents - 11.1%. Direct dependence of the degree of effectiveness of vaccination against pneumococcal disease by the age of children is determined. Conclusion. The findings suggest that implementation of the program of clinical and epidemiological monitoring and prevention of community-acquired pneumonia with use of a vaccine against pneumococcal infections in the territory of the Amur Region has a high level of medical and socio-economic efficiency.

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Clinical and Immunological Aspects of Pneumococcal Vaccination in Patients with Multiple Myeloma

Epidemiology and Vaccinal Prevention ◽

10.31631/2073-3046-2020-19-6-79-85 ◽

2021 ◽

Vol 19 (6) ◽

pp. 79-85

Author(s):

I. O. Stoma

Keyword(s):

Multiple Myeloma ◽

Pneumococcal Vaccine ◽

Pneumococcal Infection ◽

Pneumococcal Vaccination ◽

Preventive Measure ◽

Epidemiological Data ◽

Evidence Base ◽

Targeted Drugs ◽

Pneumococcal Infections ◽

Current State

Relevance. Among the groups at high risk of developing invasive pneumococcal infections, patients with multiple myeloma (MM) stand out among the highest rates of morbidity and mortality due to the presence of profound immunosuppression. Aims: to outline the current state of the problem of vaccine prevention of pneumococcal infection in patients receiving treatment for multiple myeloma, to present the evidence base for vaccination with conjugated pneumococcal vaccine. A continuous data review method was used to evaluate the studies on vaccination approaches against pneumococcal infection in patients with multiple myeloma. Conclusions. The article presents modern epidemiological data, as well as the results of original studies of clinical and immunological aspects of pneumococcal vaccination in patients with MM receiving new targeted agents and immunotherapy. The effectiveness of the use of the conjugated pneumococcal vaccine in patients treated with MM with bortezomib, lenalidomide, and ixazomib was indicated. An independent protective effect of pneumococcal vaccination has been shown as a preventive measure in a cohort of patients with MM, against the background of treatment with new targeted drugs.

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Vaccination against pneumococcal infections in adults

Clinical Microbiology and Antimicrobial Chemotherapy ◽

10.36488/cmac.2018.1.5-8 ◽

2018 ◽

Vol 20 (1) ◽

pp. 5-8 ◽

Cited By ~ 1

Author(s):

Roman S. Kozlov ◽

S.N. Avdeev ◽

Nikolay I. Briko ◽

T.N. Bilichenko ◽

M.P. Kostinov ◽

...

Keyword(s):

Adult Population ◽

Pneumococcal Infection ◽

Pneumococcal Vaccination ◽

Epidemiological Data ◽

Incidence Rates ◽

Infection Prophylaxis ◽

Pneumococcal Infections ◽

Conjugate Vaccines ◽

Key Issues ◽

The Russian Federation

The following key issues of pneumococcal infection prophylaxis were discussed during the expert council: incidence rates of community-acquired pneumococcal pneumonia and other pneumococcal infections, local epidemiological data, increases in antimicrobial resistance and pneumococcal serotypes substitution, current international and Russian clinical guidelines, practical approaches, and pneumococcal vaccination coverage of adult population in the Russian Federation. The agreement between the experts about a need to distinguish the use of conjugate vaccines and polysaccharide vaccines in different subpopulations has been achieved.

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Analysis of Morbidity Dynamics and Factors Influencing the Development of Pneumococcal Infections among the Adult Population of the Sakha Republic (Yakutia)

Epidemiology and Vaccinal Prevention ◽

10.31631/2073-3046-2018-17-4-38-45 ◽

2018 ◽

Vol 17 (4) ◽

pp. 38-45

Author(s):

A. N. Argunova ◽

Zh. V. Bondareva ◽

E. S. Prokopiev ◽

O. М. Nosikhina

Keyword(s):

Adult Population ◽

Pneumococcal Infection ◽

Pneumococcal Vaccination ◽

Mortality Rates ◽

Community Acquired Pneumonia ◽

National Average ◽

Cardiac Insufficiency ◽

Pneumococcal Infections ◽

Sakha Republic ◽

The City

The pneumococcal infection is an important issue due to its prevalence, numerous severe complications, high mortality rate and disability. However modern vaccination allows preventing of the pneumococcal infection and reduces the severity of clinical complications. This article presents the analysis of the morbidity and mortality indicators from community-acquired pneumonia and the effect of pneumococcal vaccination on its dynamic in the at-risk groups within the adult population of the Aldan area and the city of Aldan of the Sakha Republic (Yakutia). In the Aldan area pneumonia morbidity persistently exceeds the national Russian average: in 2015 – 1.5 times (499.3 per 100,000 population) and in 2016 – 1.2 times (500.8 per 100,000 population). The morbidity indicators in Aldan are comparable to the national values. The community-acquired pneumonia mortality rates in the Aldan area were 20.55 per 100,000 population in 2015, and 18.5 per 100,000 population in 2016; these values are, respectively, 4.3 and 3.8 times higher than the national average. In the city of Aldan the community-acquired pneumonia mortality rates were 9.87 per 100,000 population in 2015 and 15.8 per 100,000 population in 2016, which is more than double the national average in the Russian Federation. Pneumococcal vaccinations of the adult population using the conjugate vaccine Prevenar 13 have been observed to lower the pneumonia morbidity and respiratory infections; the vaccinations also reduced the number of hospitalizations due to condition exacerbations or decompensations among adult patients with chronic lung disorders, cardiac insufficiency, and diabetes.

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