Progress in mucosal immunization for protection against pneumococcal pneumonia.

Introduction: Lower respiratory tract infections are the fourth cause of death worldwide and pneumococcus is the leading cause of pneumonia. Nonetheless, existing pneumococcal vaccines are less effective against pneumonia than invasive diseases and serotype replacement is a major concern. Protein antigens could induce serotype-independent protection, and mucosal immunization could offer local and systemic immune responses and induce protection against pneumococcal colonization and lung infection. Areas covered: Immunity induced in the experimental human pneumococcal carriage model, approaches to address the physiological barriers to mucosal immunization and improve delivery of the vaccine antigens, different strategies already tested for pneumococcal mucosal vaccination, including live recombinant bacteria, nanoparticles, bacterium-like particles, and nanogels as well as, nasal, pulmonary, sublingual and oral routes of vaccination. Expert opinion: The most promising delivery systems are based on nanoparticles, bacterial-like particles or nanogels, which possess greater immunogenicity than the antigen alone and are considered safer than approaches based on living cells or toxoids. These particles can protect the antigen from degradation, eliminating the refrigeration need during storage and allowing the manufacture of dry powder formulations. They can also increase antigen uptake, control release of antigen and trigger innate immune responses.

Progress in mucosal immunization for protection against pneumococcal pneumonia

Introduction: Lower respiratory tract infections are the fourth cause of death worldwide and pneumococcus is the leading cause of pneumonia. Nonetheless, existing pneumococcal vaccines are less effective against pneumonia than invasive diseases and serotype replacement is a major concern. Protein antigens could induce serotype-independent protection, and mucosal immunization could offer local and systemic immune responses and induce protection against pneumococcal colonization and lung infection. Areas covered: Immunity induced in the experimental human pneumococcal carriage model, approaches to address the physiological barriers to mucosal immunization and improve delivery of the vaccine antigens, different strategies already tested for pneumococcal mucosal vaccination, including live recombinant bacteria, nanoparticles, bacterium-like particles, and nanogels as well as, nasal, pulmonary, sublingual and oral routes of vaccination. Expert opinion: The most promising delivery systems are based on nanoparticles, bacterial-like particles or nanogels, which possess greater immunogenicity than the antigen alone and are considered safer than approaches based on living cells or toxoids. These particles can protect the antigen from degradation, eliminating the refrigeration need during storage and allowing the manufacture of dry powder formulations. They can also increase antigen uptake, control release of antigen and trigger innate immune responses.

Efeito da vacina pneumocócica 10-valente em eventos de colonização nasofaríngea em crianças na cidade de Salvador-Bahia / Effect of pneumococcal 10-valent in nasopharyngeal colonization events in children in the city of Salvador, Bahia

Streptococcus pneumoniae é uma bactéria patogênica que afeta crianças e idosos em todo o mundo, sendo responsável por elevada morbidade e mortalidade, especialmente nos países em desenvolvimento onde o acesso às vacinas pneumocócicas conjugadas (PCVs) é limitado. A colonização da nasofaringe precede o desenvolvimento de infecções e as crianças são o principal reservatório deste patógeno na comunidade. As vacinas pneumocócicas conjugadas reduzem a taxa de colonização e de doenças causadas por sorotipos vacinais, entretanto, pouco se sabe sobre seu efeito em eventos na substituição de sorotipos. Os objetivos deste estudo foram determinar o efeito da vacina pneumocócica conjugada 10-valente (PCV10) na colonização nasofaríngea por pneumococos em crianças menores que um ano, saudáveis e que apresentaram doença crônica ou desordem imunológica nos períodos pré- e pós esquema vacinal primário entre maio de 2011 a janeiro de 2014 e determinar a influência desta vacina na distribuição de sorotipos, da susceptibilidade antimicrobiana e do perfil genotípico dos pneumococos. Foram investigadas 168 crianças, sendo 63 do grupo de portadores de doenças clínicas (Grupo I) e 105 do grupo de crianças sadias (Grupo II). O isolamento, a identificação e a avaliação da resistência antimicrobiana do pneumococo foram realizados através de técnicas microbiológicas convencionais. A determinação dos sorotipos capsulares foi realizada através das técnicas de reação de polimerase em cadeia multiplex e reação de Quellung. A taxa de colonização pneumocócica total foi de 24%, sendo 17% (11/63) e 28% (29/105) para os grupos I e II, respectivamente...

Streptococcus pneumoniae is a pathogenic bacterium that affects children and elderly throughout the world, accounting for high morbidity and mortality, especially in developing countries where acess to pneumococcal conjugate vaccines (PCVs) is limited. Nasopharyngeal colonization precedes the development of infections and children are the main reservoir of this pathogen in the community. The pneumococcal conjugate vaccine has been effective in reducing colonization and disease by vaccine serotypes, however, little is known about its effect on the overall rate of colonization due to serotypes replacement events. The study aims to evaluate the effect of pneumococcal conjugate vaccine on nasopharyngeal carriage in children younger than one years old, healthy, suffering from crhonic diseases or immune disorders during vaccine primary immunization with PCV-10 between may 2011 and jaanuary 2014 and the influence of this vaccine in the distribution of serotypes, antimicrobial susceptibility and genotypic profile of pneumococcus. A total of 168 children were enrolled, 63 with chronic diseases (Group I) and 105 of the group of healthy children (Group II). The isolation, identification and evaluation of antimicrobial resistance of pneumococci were made using conventional microbiological techniques. The determination of capsular serotypes was performed using the multiplex-PCR and/or Quellung reaction. Overal, the pneumococcal colonization rate was 24%, being 17% (11/63) and 28% (29/105) to group I and II, respectively...

Immunogenicity of a 7-valent pneumococcal conjugate vaccine (PCV7) and impact on carriage in Venezuelan children at risk of invasive pneumococcal diseases.

BACKGROUND AND AIMS: We evaluated the immunogenicity of the 7-valent pneumococcal conjugate vaccine (PCV7), and its impact on pneumococcal carriage in Venezuelan children at high risk for invasive pneumococcal disease (IPD). METHODS: 82 children (age 2-59 months) with sickle cell anemia (n=22), chronic heart disease (n=19), HIV infection (n=12), immune-suppressive therapy (n=11) and other IPD-predisposing conditions (n=18) were vaccinated with PCV7 according to CDC-recommended age-related immunization schedules. Blood samples were taken to determine the concentration of IgG antibody, and nasopharyngeal swabs were obtained to isolate Streptococcus pneumoniae, before the first vaccine dose and 1 month after completion of the vaccination schedule. RESULTS: Pneumococcal carriage prior to the first immunization was 27% (n=22), with the most frequently carried serotypes being vaccine serotypes 6B (22%) and 14 (13%). One month after completion of the vaccination scheme pneumococcal carriage was 22% (n=17), dominated by non-vaccine serotypes 19A (24%) and 7F (12%). Before immunization, 65% of the subjects had IgG antibody titers >0.35 µg/mL for five serotypes tested. Post-vaccination, 100% of the subjects showed titers >1.0 µg/mL for all PCV7 serotypes with geometric mean concentrations (GMC) ranging from 1.75 µg/mL (serotype 23F) to 17.16 µg/mL (serotype 14). Children previously colonized with serotype 6B had a significantly lower GMC to this serotype following immunization than children not carrying 6B prior to the first PCV dose (p<0.05). CONCLUSIONS: PCV7 is highly immunogenic in Venezuelan children at high-risk for IPD. Vaccination was associated with an immediate shift in nasopharyngeal carriage toward non-PCV7 serotypes. Finally, we observed serotype-specific hyporesponsiveness to immunization after natural carriage with the same serotype in high-risk children.