RESUMEN

BACKGROUND: Invasive pneumococcal diseases (IPD) are associated with high morbidity, mortality, and health costs worldwide, particularly in Latin America and the Caribbean (LAC). Surveillance about the distribution of serotypes causing IPD and the impact of pneumococcal vaccination is an important epidemiological tool to monitor disease activity trends, inform public health decision-making, and implement relevant prevention and control measures. OBJECTIVES: To estimate the serotype distribution for IPD and the related disease burden in LAC before, during, and after implementing the pneumococcal vaccine immunization program in LAC. METHODS: Systematic literature review following Cochrane methods of studies from LAC. We evaluated the impact of the pneumococcal vaccine on hospitalization and death during or after hospitalizations due to pneumococcal disease and serotype-specific disease over time. We also analyzed the incidence of serotyped IPD in pneumococcal conjugate vaccine PCV10 and PCV13. The protocol was registered in PROSPERO (ID: CRD42023392097). RESULTS: 155 epidemiological studies were screened and provided epidemiological data on IPD. Meta-analysis of invasive diseases in children <5 years old found that 57%-65% of causative serotypes were included in PCV10 and 66%-84% in PCV13. After PCV introduction, vaccine serotypes declined in IPD, and the emergence of non-vaccine serotypes varied by country. CONCLUSIONS: Pneumococcal conjugate vaccines significantly reduced IPD and shifted serotype distribution in Latin America and the Caribbean. PCV10/PCV13 covered 57-84% of serotypes in children under 5, with marked decline in PCV serotypes post-vaccination. Continuous surveillance remains crucial for monitoring evolving serotypes and informing public health action.

Asunto(s)

Infecciones Neumocócicas , Vacunas Neumococicas , Serogrupo , Streptococcus pneumoniae , Humanos , América Latina/epidemiología , Región del Caribe/epidemiología , Infecciones Neumocócicas/prevención & control , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/microbiología , Infecciones Neumocócicas/inmunología , Vacunas Neumococicas/inmunología , Vacunas Neumococicas/uso terapéutico , Streptococcus pneumoniae/inmunología , Streptococcus pneumoniae/clasificación , Vacunación , Costo de Enfermedad , Incidencia

RESUMEN

We evaluated whether viable and non-viable Lacticaseibacillus rhamnosus CRL1505 (Lr05V or Lr05NV, respectively) was able to improve emergency myelopoiesis induced by Streptococcus pneumoniae (Sp) infection. Adult Swiss-mice were orally treated with Lr05V or Lr05NV during five consecutive days. The Lr05V and Lr05NV groups and untreated control group received an intraperitoneal dose of cyclophosphamide (Cy-150 mg/kg). Then, the mice were nasally challenged with Sp (107 UFC/mice) on day 3 post-Cy injection. After the pneumococcal challenge, the innate and myelopoietic responses were evaluated. The control group showed a high susceptibility to pneumococcal infection, an impaired innate immune response and a decrease of hematopoietic stem cells (HSCs: Lin-Sca-1+c-Kit+), and myeloid multipotent precursors (MMPs: Gr-1+Ly6G+Ly6C-) in bone marrow (BM). However, lactobacilli treatments were able to significantly increase blood neutrophils and peroxidase-positive cells, while improving cytokine production and phagocytic activity of alveolar macrophages. This, in turn, led to an early Sp lung clearance compared to the control group. Furthermore, Lr05V was more effective than Lr05NV to increase growth factors in BM, which allowed an early HSCs and MMPs recovery with respect to the control group. Both Lr05V and Lr05NV were able to improve BM emergency myelopiesis and protection against respiratory pathogens in mice undergoing chemotherapy.

Asunto(s)

Huésped Inmunocomprometido , Lacticaseibacillus rhamnosus , Mielopoyesis , Probióticos , Streptococcus pneumoniae , Animales , Ratones , Mielopoyesis/efectos de los fármacos , Lacticaseibacillus rhamnosus/inmunología , Probióticos/administración & dosificación , Probióticos/farmacología , Streptococcus pneumoniae/inmunología , Infecciones Neumocócicas/inmunología , Infecciones Neumocócicas/microbiología , Inmunidad Innata , Modelos Animales de Enfermedad , Citocinas/metabolismo , Ciclofosfamida/farmacología , Neutrófilos/inmunología , Masculino

RESUMEN

Streptococcus pneumoniae is a human pathogen that colonizes the naso and/or oropharynx and can cause otitis, pneumonia, bacteremia and meningitis. To broaden the protection against pneumococcus, several pneumococcal proteins have been investigated as vaccine candidates. In this study we analyzed the immunological response induced by mouse subcutaneous immunization with a fusion of the Polyamine transport protein D (PotD) and a pneumolysin derivative (PdT), resulting in a hybrid rPotD-PdT protein. Immunization of mice with rPotD-PdT induced increased production of nitric oxide, indicating a higher innate immune response. In agreement, immunization of mice with the hybrid protein was more immunogenic than the individual proteins or their combination, eliciting higher antibody levels. The anti-rPotD-PdT IgG displayed increased binding onto the pneumococcal surface. Furthermore, the anti-rPotD-PdT antisera promoted superior opsonophagocytosis as compared with the other tested formulations. However, despite that the encouraging results in vitro, immunization with the hybrid was not sufficient to induce protection against sepsis with a highly virulent pneumococcal strain. taken together, the results suggest that hybrid proteins are an interesting strategy, able to promote improved immune responses, but the inclusion of other antigens may be necessary to promote protection against invasive infections caused by this bacterium.

Asunto(s)

Infecciones Neumocócicas , Streptococcus pneumoniae , Animales , Anticuerpos Antibacterianos , Formación de Anticuerpos , Proteínas Bacterianas , Ratones , Infecciones Neumocócicas/inmunología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas , Estreptolisinas

RESUMEN

INTRODUÇÃO: A doença pneumocócica (DP), causada pelo Streptococcus pneumoniae, também denominado de pneumococo, é uma condição de elevada incidência na população mundial e brasileira. Ela compreende uma gama de infecções em que se destacam a pneumonia adquirida na comunidade, otite média aguda, sinusite bacteriana e meningite bacteriana aguda. Sua manifestação mais grave ocorre nos quadros de infecção secundária de corrente sanguínea pelo pneumococo, em geral por uma pneumonia primária, e nas meningites, condições definidas como doença pneumocócica invasiva (DPI) e que apresentam elevado risco de óbito. A doença pneumocócica está entre as principais causas de internação no Brasil e também de óbito. Certas condições de base aumentam muito o risco de desenvolvimento de DP e DPI, bem como elevam sua letalidade, das quais se destaca a população idosa. A presença de comorbidades tais como doença pulmonar obstrutiva crônica, insuficiência cardíaca, asma, doença renal ou hepática crônica, diabete mélito e tabagismo, associados a redução do movimento mucociliar na mucosa respiratória e a imunossenescência tornam a população idosa muito vulnerável a DP e DPI. Além disso, é crescente a resistência bacteriana do pneumococo incrementando as taxas de mortalidade por esta condição. A prevenção da DP

Asunto(s)

Humanos , Infecciones Neumocócicas/inmunología , Vacunas Neumococicas/inmunología , Sistema Único de Salud , Brasil , Análisis Costo-Beneficio/economía

RESUMEN

Neutrophils are immune cells classically defined as pro-inflammatory effector cells. However, current accumulated evidence indicates that neutrophils have more versatile immune-modulating properties. During acute lung infection with Streptococcus pneumoniae in mice, interleukin-10 (IL-10) production is required to temper an excessive lung injury and to improve survival, yet the cellular source of IL-10 and the immunomodulatory role of neutrophils during S. pneumoniae infection remain unknown. Here we show that neutrophils are the main myeloid cells that produce IL-10 in the lungs during the first 48 h of infection. Importantly, in vitro assays with bone-marrow derived neutrophils confirmed that IL-10 can be induced by these cells by the direct recognition of pneumococcal antigens. In vivo, we identified the recruitment of two neutrophil subpopulations in the lungs following infection, which exhibited clear morphological differences and a distinctive profile of IL-10 production at 48 h post-infection. Furthermore, adoptive transfer of neutrophils from WT mice into IL-10 knockout mice (Il10-/- ) fully restored IL-10 production in the lungs and reduced lung histopathology. These results suggest that IL-10 production by neutrophils induced by S. pneumoniae limits lung injury and is important to mediate an effective immune response required for host survival.

Asunto(s)

Interleucina-10/metabolismo , Pulmón/patología , Neutrófilos/metabolismo , Infecciones Neumocócicas/inmunología , Streptococcus pneumoniae/fisiología , Traslado Adoptivo , Animales , Antiinflamatorios , Células Cultivadas , Inmunidad Celular , Interleucina-10/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Infiltración Neutrófila

RESUMEN

Pneumococcal infections are common and serious complications of HIV-1 disease. Prevention has been compromised by the limited magnitude and quality of Ab responses to T cell-independent type 2 pneumococcal capsular polysaccharides (PPS). The pneumococcal polysaccharide-protein conjugate vaccine-13 (PCV-13) contains PPS conjugated to the T cell-dependent protein (diphtheria toxoid [DT] [CRM197]). We investigated the differential response to PPS and DT by human Ab-secreting B cells (ASC) after immunization with PCV-13 in newly diagnosed healthy HIV+ and control adults. The numbers of PPS-specific IgG ASC increased significantly and similarly in HIV+ and controls. However, DT-specific IgG ASC increased in controls but not HIV+ subjects. To determine the cellular basis of these disparate responses to DT and PPS, we characterized the frequency and activation of T follicular helper (Tfh) cells, the predominant T cell subset providing B cell help. Expression of inducible T cell costimulator (ICOS), which sustains Tfh function and phenotype, increased significantly among controls, when compared with the HIV+ group. Increases in ICOS+ Tfh correlated with changes in T-dependent, DT-specific IgG ASC in controls but not in HIV+ In contrast, ICOS expression did not correlate with T cell-independent type 2 PPS-specific ASC in either group. Of note, upon optimized ex vivo stimulation, CD4 T cells from HIV+ subjects differentiated into Tfh cells and formed synapses with Raji B cells at frequencies similar to that of controls. In summary, PCV-13-induced increase in ICOS expression on Tfh was associated with responses to DT, which was compromised in recently diagnosed healthy HIV+ adults and can be restored ex vivo by providing effective Tfh-differentiating signals.

Asunto(s)

Infecciones Oportunistas Relacionadas con el SIDA/prevención & control , Inmunidad Adaptativa , VIH-1/inmunología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/inmunología , Streptococcus pneumoniae/inmunología , Células T Auxiliares Foliculares/inmunología , Vacunación/métodos , Vacunas Conjugadas/inmunología , Infecciones Oportunistas Relacionadas con el SIDA/sangre , Infecciones Oportunistas Relacionadas con el SIDA/inmunología , Infecciones Oportunistas Relacionadas con el SIDA/virología , Adolescente , Adulto , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Linfocitos B/inmunología , Estudios de Casos y Controles , Femenino , Humanos , Inmunogenicidad Vacunal , Proteína Coestimuladora de Linfocitos T Inducibles/metabolismo , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Infecciones Neumocócicas/sangre , Infecciones Neumocócicas/inmunología , Infecciones Neumocócicas/microbiología , Resultado del Tratamiento , Adulto Joven

RESUMEN

BACKGROUND: Pneumococcus remains an important cause of morbidity in pregnant women with HIV and their infants. We compared the safety and immunogenicity of PCV-10 and PPV-23 with placebo administered in pregnancy. METHODS: This double-blind, multicentre, randomised controlled trial was done at eight outpatient clinics in Brazil. Eligible participants were adult women with HIV who were pregnant at a gestational age between 14 weeks and less than 34 weeks and who were taking antiretroviral therapy at study entry. Participants were randomly assigned (1:1:1) to receive either PCV-10, PPV-23, or placebo. Participants and study teams were unaware of treatment allocation. Antibodies against seven vaccine serotypes in PCV-10 and PPV-23 were measured by ELISA. The primary outcomes were maternal and infant safety assessed by the frequency of adverse events of grade 3 or higher; maternal seroresponse (defined as ≥2-fold increase in antibodies from baseline to 28 days after immunisation) against five or more serotypes; and infant seroprotection (defined as anti-pneumococcus antibody concentration of ≥0·35 µg/mL) against five or more serotypes at 8 weeks of life. The study was powered to detect differences of 20% or higher in the primary immunological outcomes between treatment groups. This trial is registered with ClinicalTrials.gov, NCT02717494. FINDINGS: Between April 1, 2016, and Nov 30, 2017, we enrolled 347 pregnant women with HIV, of whom 116 were randomly assigned to the PCV-10 group, 115 to the PPV-23 group, and 116 to the placebo group. One participant in the PCV-10 group did not receive the vaccine and was excluded from subsequent analyses. The frequency of adverse events of grade 3 or higher during the first 4 weeks was similar in the vaccine and placebo groups (3% [90% CI 1-7] for the PCV-10 group, 2% [0-5] for the PPV-23 group, and 3% [1-8] for the placebo group). However, injection site and systemic grade 2 adverse reactions were reported more frequently during the first 4 weeks in the vaccine groups than in the placebo group (14% [9-20] for the PCV-10 group, 7% [4-12] for the PPV-23 group, and 3% [1-7] for the placebo group). The frequency of grade 3 or higher adverse effects was similar across maternal treatment groups (20% [14-27] for the PCV-10 group, 21% [14-28] for the PPV-23 group, and 20% [14-27] for the placebo group). Seroresponses against five or more serotypes were present in 74 (65%) of 114 women in the PCV-10 group, 72 (65%) of 110 women in the PPV-23 group, and none of the 113 women in the placebo group at 4 weeks post vaccination (p<0·0001 for PPV-23 group vs placebo and PCV-10 group vs placebo). Seroresponse differences of 20% or higher in vaccine compared with placebo recipients persisted up to 24 weeks post partum. At birth, 76 (67%) of 113 infants in the PCV-10 group, 62 (57%) of 109 infants in the PPV-23 group, and 19 (17%) of 115 infants in the placebo group had seroprotection against five or more serotypes (p<0·0001 for PPV-23 vs placebo and PCV-10 vs placebo). At 8 weeks, the outcome was met by 20 (19%) of 108 infants in the PCV-10 group, 24 (23%) of 104 infants in the PPV-23 group, and one (1%) of 109 infants in the placebo group (p<0·0001). Although a difference of 20% or higher compared with placebo was observed only in the infants who received PPV-23 at 8 weeks of life, the difference between the two vaccine groups was not appreciable. INTERPRETATION: PCV-10 and PPV-23 were equally safe and immunogenic in pregnant women with HIV and conferred similar levels of seroprotection to their infants. In areas in which childhood PCV administration decreased the circulation of PCV serotypes, PPV-23 administration to pregnant women with HIV might be more advantageous than PCV by virtue of including a broader range of serotypes. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Asunto(s)

Anticuerpos Antibacterianos/inmunología , Infecciones por VIH/complicaciones , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/administración & dosificación , Adulto , Fármacos Anti-VIH/uso terapéutico , Brasil , Método Doble Ciego , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Humanos , Lactante , Recién Nacido , Masculino , Placenta/inmunología , Infecciones Neumocócicas/inmunología , Infecciones Neumocócicas/microbiología , Vacunas Neumococicas/efectos adversos , Embarazo , Mujeres Embarazadas , Streptococcus pneumoniae/inmunología , Adulto Joven

RESUMEN

Older adults are at increased risk of pneumococcal disease. This work aims to evaluate whether there is any decrease in serum IgG against variants of the antigens Pneumococcal surface protein A (PspA) and Pneumococcal surface protein C (PspC) in healthy adults with increasing age. Levels of IgG against PspA and PspC variants were determined by ELISA in serum samples comparing volunteers 18-30 years of age with volunteers who were 50-70+ before and after an experimental pneumococcal colonization challenge. The serotype 6B strain used in the challenge belongs to a minor group of pneumococcal isolates expressing two PspC variants. There was a decrease in levels of IgG with increasing age for the most common PspA variants and for all PspC variants analyzed. No correlation was found between basal levels of IgG against these antigens and protection against colonization. There was an increase in levels of IgG against PspA variants that are more cross-reactive with the variant expressed by the challenge strain post challenge in younger individuals who became colonized. Since the challenge strain used in our study expresses two different PspC variants, an increase in serum IgG against all PspC variants tested was observed in younger individuals who became colonized. For some of the antigen variants tested, a decrease in serum IgG was observed in young volunteers who were challenged but did not become colonized. Serum IgG antibodies against PspA and PspC variants thus decrease with age in healthy adults, but there is no correlation between levels of IgG against these antigens and protection against human experimental colonization. Though no correlation between naturally induced serum IgG antibodies against PspA and PspC and protection against colonization was observed, these results do not rule out the protective potential of these antigens as vaccines against pneumococcal infections.

Asunto(s)

Envejecimiento/inmunología , Anticuerpos Antibacterianos/sangre , Proteínas Bacterianas/inmunología , Infecciones Neumocócicas/inmunología , Adolescente , Adulto , Anciano , Anticuerpos Antibacterianos/inmunología , Susceptibilidad a Enfermedades , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infecciones Neumocócicas/sangre

RESUMEN

Resolution failure of exacerbated inflammation triggered by Influenza A virus (IAV) prevents return of pulmonary homeostasis and survival, especially when associated with secondary pneumococcal infection. Therapeutic strategies based on pro-resolving molecules have great potential against acute inflammatory diseases. Angiotensin-(1-7) [Ang-(1-7)] is a pro-resolving mediator that acts on its Mas receptor (MasR) to promote resolution of inflammation. We investigated the effects of Ang-(1-7) and the role of MasR in the context of primary IAV infection and secondary pneumococcal infection and evaluated pulmonary inflammation, virus titers and bacteria counts, and pulmonary damage. Therapeutic treatment with Ang-(1-7) decreased neutrophil recruitment, lung injury, viral load and morbidity after a primary IAV infection. Ang-(1-7) induced apoptosis of neutrophils and efferocytosis of these cells by alveolar macrophages, but had no direct effect on IAV replication in vitro. MasR-deficient (MasR-/-) mice were highly susceptible to IAV infection, displaying uncontrolled inflammation, increased viral load and greater lethality rate, as compared to WT animals. Ang-(1-7) was not protective in MasR-/- mice. Interestingly, Ang-(1-7) given during a sublethal dose of IAV infection greatly reduced morbidity associated with a subsequent S. pneumoniae infection, as seen by decrease in the magnitude of neutrophil influx, number of bacteria in the blood leading to a lower lethality. Altogether, these results show that Ang-(1-7) is highly protective against severe primary IAV infection and protects against secondary bacterial infection of the lung. These effects are MasR-dependent. Mediators of resolution of inflammation, such as Ang-(1-7), should be considered for the treatment of pulmonary viral infections.

Asunto(s)

Angiotensina I/uso terapéutico , Antiinflamatorios/uso terapéutico , Fragmentos de Péptidos/uso terapéutico , Infecciones Neumocócicas/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Proteínas Proto-Oncogénicas/inmunología , Receptores Acoplados a Proteínas G/inmunología , Células A549 , Angiotensina I/farmacología , Animales , Antiinflamatorios/farmacología , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Citocinas/inmunología , Perros , Humanos , Virus de la Influenza A , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/patología , Células de Riñón Canino Madin Darby , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Fragmentos de Péptidos/farmacología , Peroxidasa/inmunología , Fagocitosis/efectos de los fármacos , Infecciones Neumocócicas/inmunología , Infecciones Neumocócicas/patología , Neumonía Viral/inmunología , Neumonía Viral/patología , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas/genética , Receptores Acoplados a Proteínas G/genética , Streptococcus pneumoniae

RESUMEN

Conjugate vaccines against encapsulated pathogens like Streptococcus pneumoniae face many challenges, including the existence of multiple serotypes with a diverse global distribution that constantly requires new formulations and higher coverage. Multivalency is usually achieved by combining capsular polysaccharide-protein conjugates from invasive serotypes, and for S. pneumoniae, this has evolved from 7- up to 20-valent vaccines. These glycoconjugate formulations often contain high concentrations of carrier proteins, which may negatively affect glycoconjugate immune response. This work broadens the scope of an efficient multicomponent strategy, leading to multivalent pneumococcal glycoconjugates assembled in a single synthetic operation. The bioconjugation method, based on the Ugi four-component reaction, enables the one-pot incorporation of two different polysaccharide antigens to a tetanus toxoid carrier, thus representing the fastest approach to achieve multivalency. The reported glycoconjugates incorporate three combinations of capsular polysaccharides 1, 6B, 14, and 18C from S. pneumoniae. The glycoconjugates were able to elicit functional specific antibodies against pneumococcal strains comparable to those shown by mixtures of the two monovalent glycoconjugates.

Asunto(s)

Glicoconjugados/química , Vacunas Neumococicas/química , Vacunas Conjugadas/química , Animales , Técnicas de Química Sintética , Glicoconjugados/síntesis química , Glicoconjugados/inmunología , Glicoconjugados/uso terapéutico , Humanos , Ratones , Modelos Moleculares , Infecciones Neumocócicas/inmunología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/síntesis química , Vacunas Neumococicas/inmunología , Vacunas Neumococicas/uso terapéutico , Conejos , Streptococcus pneumoniae/inmunología , Vacunas Conjugadas/inmunología , Vacunas Conjugadas/uso terapéutico

RESUMEN

The nasal priming with nonviable Lactobacillus rhamnosus CRL1505 (NV1505) or its purified peptidoglycan (PG1505) differentially modulates the respiratory innate immune response in infant mice, improving their resistance to primary respiratory syncytial virus (RSV) infection and secondary pneumococcal pneumonia. In association with the protection against RSV-pneumococcal superinfection, it was found that NV1505 or PG1505 significantly enhance the numbers of CD11c+SiglecF+ alveolar macrophages (AMs) producing interferon (IFN)-ß. In this work, we aimed to further advance in the characterization of the beneficial effects of NV1505 and PG1505 in the context of a respiratory superinfection by evaluating whether their immunomodulatory properties are dependent on AM functions. Macrophage depletion experiments and a detailed study of their production of cytokines and antiviral factors clearly demonstrated the key role of this immune cell population in the improvement of both the reduction of pathogens loads and the protection against lung tissue damage induced by the immunobiotic CRL1505 strain. Studies at basal conditions during primary RSV or S. pneumoniae infections, as well as during secondary pneumococcal pneumonia, brought the following five notable findings regarding the immunomodulatory effects of NV1505 and PG1505: (a) AMs play a key role in the beneficial modulation of the respiratory innate immune response and protection against RSV infection, (b) AMs are necessary for improved protection against primary and secondary pneumococcal pneumonia, (c) the generation of activated/trained AMs would be essential for the enhanced protection against respiratory pathogens, (d) other immune and nonimmune cell populations in the respiratory tract may contribute to the protection against bacterial and viral infections, and (e) the immunomodulatory properties of NV1505 and PG1505 are strain-specific. These findings significantly improve our knowledge about the immunological mechanisms involved in the modulation of respiratory immunity induced by beneficial microbes.

Asunto(s)

Factores Inmunológicos/uso terapéutico , Macrófagos Alveolares/inmunología , Peptidoglicano/uso terapéutico , Infecciones Neumocócicas/inmunología , Infecciones por Virus Sincitial Respiratorio/inmunología , Animales , Antígenos CD11/genética , Antígenos CD11/metabolismo , Células Cultivadas , Chlorocebus aethiops , Inmunidad Innata , Factores Inmunológicos/farmacología , Lacticaseibacillus rhamnosus/metabolismo , Macrófagos Alveolares/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Peptidoglicano/farmacología , Infecciones Neumocócicas/terapia , Infecciones por Virus Sincitial Respiratorio/terapia , Lectinas Similares a la Inmunoglobulina de Unión a Ácido Siálico/genética , Lectinas Similares a la Inmunoglobulina de Unión a Ácido Siálico/metabolismo , Células Vero

RESUMEN

OBJECTIVES: To evaluate the cost-effectiveness of introducing a domestic pneumococcal conjugate vaccine (PCV7-TT) into the Cuban National Immunization Program (NIP). METHODS: We compared PCV7-TT given at two, four and six months of age to a scenario without PCV7-TT, over a ten-year period (2020-2029). We calculated the cost (Cuban pesos - CUP) per Disability Adjusted Life Year (DALY) averted from a Government perspective. We compared results from a static cohort model and a parsimonious prediction model informed by the serotype distribution among pneumococcal carriers and cases. We ran probabilistic and deterministic uncertainty analyses. RESULTS: PCV7-TT could prevent 6897 (95% uncertainty interval, 4344-8750) hospitalizations and 189 (115-253) deaths in children <5 years of age, over the period 2020-2029. This could cost around 25 million (20-31) discounted CUP but would be offset by treatment cost savings of around 23 million (14-31). A parsimonious model predicted less favourable impact and cost-effectiveness but the cost per DALY averted was still less than 0.4 times the current GDP per capita. CONCLUSIONS: PCV7-TT is likely to be cost-effective in Cuba. The impact of the vaccine would need to be carefully monitored following its introduction into the NIP.

Asunto(s)

Programas de Inmunización/economía , Infecciones Neumocócicas/economía , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/administración & dosificación , Vacunas Neumococicas/economía , Algoritmos , Preescolar , Estudios de Cohortes , Análisis Costo-Beneficio , Cuba , Femenino , Costos de la Atención en Salud , Hospitalización/economía , Humanos , Lactante , Masculino , Infecciones Neumocócicas/inmunología , Infecciones Neumocócicas/microbiología , Vacunas Neumococicas/inmunología , Años de Vida Ajustados por Calidad de Vida , Streptococcus pneumoniae/inmunología , Vacunas Conjugadas/administración & dosificación , Vacunas Conjugadas/economía , Vacunas Conjugadas/inmunología

RESUMEN

The available pneumococcal conjugate vaccines provide protection against only those serotypes that are included in the vaccine, which leads to a selective pressure and serotype replacement in the population. An alternative low-cost, safe and serotype-independent vaccine was developed based on a nonencapsulated pneumococcus strain. This study evaluates process intensification to improve biomass production and shows for the first time the use of perfusion-batch with cell recycling for bacterial vaccine production. Batch, fed-batch, and perfusion-batch were performed at 10 L scale using a complex animal component-free culture medium. Cells were harvested at the highest optical density, concentrated and washed using microfiltration or centrifugation to compare cell separation methods. Higher biomass was achieved using perfusion-batch, which removes lactate while retaining cells. The biomass produced in perfusion-batch would represent at least a fourfold greater number of doses per cultivation than in the previously described batch process. Each strategy yielded similar vaccines in terms of quality as evaluated by western blot and animal immunization assays, indicating that so far, perfusion-batch is the best strategy for the intensification of pneumococcal whole-cell vaccine production, as it can be integrated to the cell separation process keeping the same vaccine quality.

Asunto(s)

Técnicas de Cultivo Celular por Lotes/instrumentación , Vacunas Neumococicas/inmunología , Streptococcus pneumoniae/inmunología , Animales , Técnicas de Cultivo Celular por Lotes/métodos , Biomasa , Reactores Biológicos , Diseño de Equipo , Femenino , Humanos , Inmunización , Ratones Endogámicos C57BL , Infecciones Neumocócicas/inmunología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/uso terapéutico , Neumonía Neumocócica/inmunología , Neumonía Neumocócica/prevención & control , Streptococcus pneumoniae/citología

RESUMEN

Introduction: Serotype replacement - a consequence of polysaccharide vaccine use - will continue to drive the inclusion of new serotypes on conjugate vaccines, increasing production complexity and costs, and making an already expensive vaccine less accessible to developing countries, where prevalence is higher and resources available for health systems, scarcer. Serotype-independent formulations are a promising option, but so far they have not been successful in reducing colonization/transmission.Areas covered: Protein-based and whole-cell vaccine candidates studied in the past 30 years. Challenges for serotype-independent vaccine development and alternative approaches.Expert opinion: Clinical trials performed so far demonstrated the importance to establish more reliable animal models and better correlates of protection. Defining appropriate endpoints for clinical trials of serotype-independent vaccine candidates has been a challenge. Inhibition of colonization has been evaluated, but concern on the extent of bacterial elimination is still a matter of debate. Challenges on establishing representative sites for clinical trials, sample sizes and appropriate age groups are discussed. On a whole, although many challenges will have to be overcome, establishing protein-based antigens as serotype-independent vaccines is still the best alternative against the huge burden of pneumococcal diseases in the world.

Asunto(s)

Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/administración & dosificación , Animales , Antígenos Bacterianos/inmunología , Proteínas Bacterianas/inmunología , Humanos , Infecciones Neumocócicas/inmunología , Vacunas Neumococicas/inmunología , Serogrupo , Vacunas Conjugadas/administración & dosificación

RESUMEN

The effect of Lactobacillus rhamnosus CRL1505 (Lr) on macrophages (Ma) and dendritic cells (DC) in the orchestration of anti-pneumococcal immunity was studied using malnutrition and pneumococcal infection mouse models. Monocytes (Mo), Ma, and DC in two groups of malnourished mice fed with balanced diet (BCD) were studied through flow cytometry; one group was nasally administered with Lr (BCD+Lr group), and the other group was not (BCD group). Well-nourished (WNC) and malnourished (MNC) mice were used as controls.Malnutrition affected the number of respiratory and splenic mononuclear phagocytes. The BCD+Lr treatment, unlike BCD, was able to increase and normalize lung Mo and Ma. The BCD+Lr mice were also able to upregulate the expression of the activation marker MHC II in lung DC and to improve this population showing a more significant effect on CD11b+ DC subpopulation. At post-infection, lung Mo values were higher in BCD+Lr mice than in BCD mice and similar to those obtained in WNC group. Although both repletion treatments showed similar values of lung Ma post-infection, the Ma activation state in BCD+Lr mice was higher than that in BCD mice. Furthermore, BCD+Lr treatment was able to normalize the number and activation of splenic Ma and DC after the challenge.Lr administration stimulates respiratory and systemic mononuclear phagocytes. Stimulation of Ma and DC populations would increase the microbicide activity and improve the adaptive immunity through its antigen-presenting capacity. Thus, Lr contributes to improved outcomes of pneumococcal infection in immunocompromised hosts.

Asunto(s)

Inmunidad , Lacticaseibacillus rhamnosus , Desnutrición/terapia , Infecciones Neumocócicas/terapia , Probióticos/administración & dosificación , Animales , Células Dendríticas/citología , Pulmón/inmunología , Macrófagos/citología , Masculino , Ratones , Infecciones Neumocócicas/inmunología , Bazo/inmunología

RESUMEN

Introduction: Evidence on the interchangeability between the two pediatric pneumococcal conjugate vaccines (PCVs) - pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) and 13-valent PCV (PCV13) - is limited but growing. We performed a systematic literature review to summarize evidence for PHiD-CV/PCV13 interchangeability regarding immunogenicity, safety, and effectiveness against pneumococcal disease. Areas covered: Seven records disclosing results from six studies on PHiD-CV/PCV13 interchangeability were identified. Four clinical trials showed that mixed schedules with a PHiD-CV-to-PCV13 switch at boosting or a PCV13-to-PHiD-CV switch during priming or at boosting were immunogenic with no apparent safety concerns. Two observational studies in the context of a programmatic PHiD-CV-to-PCV13 switch showed similarly high effectiveness against overall invasive pneumococcal disease with a mixed PHiD-CV/PCV13 schedule and a PCV13-only schedule. No effectiveness data for a PCV13-to-PHiD-CV switch and no immunogenicity/safety/effectiveness data for a PHiD-CV-to-PCV13 switch during priming were found. Expert opinion: For epidemiological or programmatic reasons, several local/national authorities have switched PCVs in their immunization programs. Consequently, children have received mixed schedules. Although herd immunity may obscure the individual effect, the limited data are reassuring. Additional evidence from these settings - especially effectiveness or impact data - may provide the necessary information for authorities to make informed decisions on interchanging PCVs.

Asunto(s)

Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/administración & dosificación , Humanos , Inmunidad Colectiva , Programas de Inmunización , Inmunización Secundaria/métodos , Inmunogenicidad Vacunal , Lactante , Infecciones Neumocócicas/inmunología , Vacunas Neumococicas/inmunología , Vacunas Conjugadas

Asunto(s)

Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/inmunología , Vacunas Neumococicas/uso terapéutico , Serogrupo , Niño , Europa (Continente) , Humanos , Nasofaringe/microbiología , Estudios Observacionales como Asunto , Infecciones Neumocócicas/inmunología , Infecciones Neumocócicas/microbiología , Prevalencia , Vacunas Conjugadas/uso terapéutico

RESUMEN

BACKGROUND: The 13-valent pneumococcal conjugate vaccine (PCV13) has been commercially available in Brazil since 2010. We investigated the carriage prevalence, capsular types, and antimicrobial resistance among pneumococci isolated from children immunized with PCV13 in Brazil. METHODS: We analyzed 500 children < 6 years old attending public (n = 270) and private (n = 230) clinics in Niterói/RJ, Brazil, in 2014. We determined the antimicrobial susceptibility and capsular types for all isolates. RESULTS: Thirty-eight (7.6%) of 500 children had received at least one PCV13 dose. Since only two (0.7%) of 270 children at the public clinic were vaccinated with PCV13, major analyses focused on 36 (15.7%) of 230 children attending private clinics. Nine (25%) of 36 children were pneumococcal carriers. Characteristics associated with carriage were age ≥ 2 years, cough/expectoration, and childcare center attendance (p ≤ 0.01). The capsular types found were 15B/C (n = 2), 6C, 11A/D, 16F, 23A, and 23F. Two isolates were non-typeable (NT). Three (33.3%) isolates were multidrug resistant. We found four (44.4%) penicillin non-susceptible pneumococci, with penicillin and ceftriaxone MICs ranging from 0.12 to 4.0 µg/ml and 0.023-0.5 µg/ml, respectively. We also detected two (22.2%) erythromycin-resistant isolates (MICs of 3.0 and 256 µg/ml). CONCLUSIONS: Colonization with PCV13 serotype was rare among the vaccinated children. Increasing PCV13 coverage might help reduce the frequency of major serotypes currently associated with invasive pneumococcal diseases in Brazil, such as 3 and 19A. The isolation of multidrug-resistant serotype 6C and NT isolates in carriage, however, requires close monitoring.

Asunto(s)

Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/uso terapéutico , Streptococcus pneumoniae/patogenicidad , Brasil , Niño , Preescolar , Farmacorresistencia Bacteriana , Femenino , Humanos , Lactante , Masculino , Pruebas de Sensibilidad Microbiana , Infecciones Neumocócicas/inmunología , Serogrupo , Streptococcus pneumoniae/inmunología , Vacunas Conjugadas/uso terapéutico

RESUMEN

Respiratory tract infections and invasive disease caused by Streptococcus pneumoniae in high-risk groups are a major global health problem. Available human vaccines have reduced immunogenicity and low immunological memory in these populations, as well as high cost as a public health strategy in poor communities. In addition, no single pneumococcal protein antigen has been able to elicit protection comparable to that achieved using protein-polysaccharide conjugate vaccines. In this context, chimeric pneumococcal proteins raise as potential good vaccine candidates because of their simplicity of production and reduced cost. The aim of this work was to study whether the nasal immunization of infant mice with the recombinant chimeric pneumococcal protein (PSFP) was able to improve resistance to S. pneumoniae, and whether the immunomodulatory strain Lactobacillus rhamnosus CRL1505 or its cell wall (CW1505) could be used as effective mucosal adjuvants. Our results showed that the nasal immunization with PSPF improved pneumococcal-specific IgA and IgG levels in broncho-alveolar lavage (BAL), reduced lung bacterial counts, and avoided dissemination of pneumococci into the blood. Of interest, immunization with PSPF elicited cross-protective immunity against different pneumococcal serotypes. It was also observed that the nasal immunization of infant mice with PSPF+CW1505 significantly increased the production of pneumococcal-specific IgA and IgG in BAL, as well as IgM and IgG in serum when compared with PSPF alone. PSPF+CW1505 immunization also improved the reduction of pneumococcal lung colonization and its dissemination in to the bloodstream when compared to PSPF alone. Our results suggest that immunization with PSPF together with the cell wall of the immunomodulatory strain L. rhamnosus CRL1505 as a mucosal adjuvant could be an interesting alternative to improve protection against pneumococcal infection in children.

Asunto(s)

Infecciones Neumocócicas/inmunología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/administración & dosificación , Adyuvantes Inmunológicos/administración & dosificación , Administración Intranasal , Animales , Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos/administración & dosificación , Proteínas Bacterianas/administración & dosificación , Proteínas Bacterianas/inmunología , Pared Celular/inmunología , Niño , Protección Cruzada , Citocinas/sangre , Humanos , Inmunidad Mucosa , Inmunización , Lacticaseibacillus rhamnosus/inmunología , Pulmón/inmunología , Pulmón/microbiología , Masculino , Ratones , Infecciones Neumocócicas/microbiología , Vacunas Neumococicas/inmunología , Neumonía Neumocócica/inmunología , Neumonía Neumocócica/microbiología , Neumonía Neumocócica/prevención & control , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/inmunología , Streptococcus pneumoniae/inmunología

RESUMEN

INTRODUCTION: Pneumococcal infections are a public health problem in older adults. In Chile there are two vaccines at this time, PPSV23 and PCV13. The first has lower immunogenicity and effectiveness in preventing pneumococcal pneumonia and a lower cost than PCV13. OBJECTIVE: To determine the cost-effectiveness of PCV13 versus PPSV23 in adults 18 years old and over in the Chilean Health System. MATERIAL AND METHOD: A cost-utility study was performed using the Markov model (population data for a time horizon of 10 years). Utilities and epidemiological data were obtained from the literature and costs from the Chilean Public sector. Vaccine's costs and quality-adjusted life years (QALYs) were determined and compared. RESULTS: PCV13 vaccination program in adults (≥18 years), generated savings of $42,195 USD and an increase of 6,820 QALYs, avoiding 107 cases of bacteremia, 13 meningitis, 6,706 inpatient pneumonia, 4,509 outpatient pneumonia and 1,189 deaths compared to PPSV23 without variation on sensitivity analysis on high impact variables. For the subgroup of patients over 65 years old PCV13 generates savings of $ 32,105.94USD and produces 5,430 QALYs more compared to PPSV23. CONCLUSION: PCV13 is dominant. A PCV13 vaccination program saves costs to the public system, reduces mortality and morbidity; these results are robust.

Asunto(s)

Análisis Costo-Beneficio , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/economía , Neumonía Neumocócica/prevención & control , Vacunas Conjugadas/economía , Adulto , Anciano , Chile , Humanos , Persona de Mediana Edad , Infecciones Neumocócicas/inmunología , Vacunas Neumococicas/administración & dosificación , Neumonía Neumocócica/inmunología , Calidad de Vida