Safety and Immunogenicity of Heptavalent Pneumococcal Vaccine Conjugated to CRM197 in United States Infants

Rennels, Margaret B.; Edwards, Kathryn M.; Keyserling, Harry L.; Reisinger, Keith S.; Hogerman, Deborah A.; Madore, Dace V.; Chang, Ih; Paradiso, Peter R.; Malinoski, Frank; Kimura, Alan

doi:10.1542/peds.101.4.604

Cited by 358 publications

(200 citation statements)

References 19 publications

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“…Moreover these conjugate vaccines will induce a memory response with a rise of antibody titer after several rounds of Table 1 Box 1 immunization and a booster response several months later . Surprisingly, in older infants and in adults, the same conjugate vaccine [21][22][23][24] does not induce a memory response but a response similar to the one obtained with the plain CPS preparation , even though the [25][26][27][28] response to the conjugate appears in some cases more robust . We have shown that humans display a circulating marginal zone B cell population which is involved in TI response and which diversifies its Ig receptor in the absence of cognate T-B interactions.…”

Section: Paradoxmentioning

confidence: 99%

Vaccination against encapsulated bacteria in humans: paradoxes

Weller

Reynaud

Weill

2005

Trends in Immunology

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Infection with encapsulated bacteria can be prevented by vaccination with capsular polysaccharides, either plain or conjugated to a protein carrier. But results concerning these vaccinations raise several paradoxes. Polysaccharides from encapsulated bacteria are generally considered to be Tindependent antigens unable to trigger a T-dependent germinal center reaction, but strikingly, anti-polysaccharide antibodies are often mutated in humans. Polysaccharide-protein conjugate vaccines are able to induce a true T-dependent memory response with a rise in antibody titers and a switch to high affinity-IgG antibodies in children below 2 years of age, but neither the plain nor the conjugate vaccine can induce memory in older infants and adults. We propose some explanations to these paradoxes based on our recent observation that humans display a circulating splenic marginal zone B cell population with a pre-diversified immunoglobulin repertoire in charge of the immune response to T-independent vaccines. The impact of diseases generated by encapsulated bacteria has been underlined in many contexts and it is estimated that they are responsible for millions of children s deaths each year . Nevertheless, when looking at the abundant literature on immune responses to ' [1] encapsulated bacteria after vaccination by either plain or conjugated capsular polysaccharide vaccines, some paradoxes emerge which we would like to discuss. MESH Keywords Paradox 1It is generally accepted that bacterial capsular polysaccharides (CPS) are TI antigens that trigger specific B cells residing in the splenic marginal zone to secrete antibodies with opsonophagocytic properties against these bacteria . In rodents in which these responses have [2] been mostly studied, immunization do not induce an extensive proliferation within B cell follicles, neither the formation of germinal centers, and are for most of them taken care by unmutated germline antibodies . In humans on the contrary, the splenic marginal zone [3][4][5] contains B cells with mutated Ig receptors and mutated antibodies are raised in responses to encapsulated bacteria, these mutations [6][7][8] being responsible for the antibodies avidity for the immunizing antigen , . In all species, these TI responses do not trigger any [9 10] memory, the B cells engaged being able very rapidly to switch isotype and to secrete large amount of antibodies. These plasma cells can remain in the organism for various lengths of time, after which the response wanes out , . To account for the presence in humans of [11 12] mutated antibodies during a T-independent immune response that cannot normally trigger a cognate T-B dependent germinal center reaction, the classical explanation put forward by authors is that such responses are in fact taken care by memory B cells that bona fide have been primed by a previous encounter with the pathogen, either during an infection or by silent carriage . These memory B [13][14][15] cells would then eventually reside in the splenic marginal zone where they ...

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Section: Paradoxmentioning

confidence: 99%

Vaccination against encapsulated bacteria in humans: paradoxes

Weller

Reynaud

Weill

2005

Trends in Immunology

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“…Foi avaliada a ocorrência de doenças invasivas produzidas a partir de 14 dias após o término das três primeiras doses, que se mostrou muito alta 89,90,15 (Tabela 2).…”

Section: Vacinas Antipneumocócicasunclassified

Vacinas e o trato respiratório: o que devemos saber?

Farhat¹,

Cintra²,

Tregnaghi³

2002

J. Pediatr. (Rio J.)

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ResumoObjetivo: o presente artigo tem por objetivo apresentar uma revisão acerca das principais vacinas utilizadas na população pediá-trica, com impacto direto na prevenção dos processos infecciosos infantis do trato respiratório. Fontes dos dados:foram analisadas informações de artigos publicados em revistas científicas nacionais e internacionais, selecionados por busca direta ou por pesquisa nas bases de dados Lilacs e Medline.Síntese dos dados: o artigo foi estruturado em tópicos, apresentando questões relativas à imunização contra os patógenos freqüen-tes do trato respiratório em humanos, como Haemophilus influenza, vírus influenza, vírus respiratório sincicial e Streptococcus pneumoniae.Conclusões: a prevenção de doenças respiratórias, através de imunização, constitui-se numa das principais medidas para controle das infecções respiratórias. O acesso da população a estas novas vacinas, principalmente contra Haemophilus influenza, o que já ocorre há alguns anos com reconhecida eficácia, e agora contra o Streptococcus pneumoniae (vacina heptavalente) apontam para uma nova perspectiva, direcionada para o manejo da doença respiratória infantil. Em populações de risco, o controle da doença de etiologia viral através da imunização de forma ativa contra o vírus influenza, e de forma passiva para o vírus respiratório sincicial, também constituem medidas eficazes na redução da doença respiratória.J Pediatr (Rio J) 2002; 78 (Supl.2): S195-S204:vacinas, Haemophilus influenza, vírus influenza, vírus respiratório sincicial, Streptococcus pneumoniae. AbstractObjective: this article aims at presenting a review of the main vaccines used in the pediatric population with direct impact on the prevention of infectious processes of the respiratory tract in children.Sources: data from articles published in national and international scientific journals. The data were selected by means of direct search or search in the Lilacs and Medline databases. Summary of the findings: this article was structured in topics, presenting issues related to immunization against frequent pathogens of the respiratory tract in human beings: Haemophilus influenza, influenza virus, respiratory syncytial virus and Streptococcus pneumoniae.Conclusions: the prevention of respiratory diseases through immunization is one of the main measures for the control of respiratory infection. These new vaccines, especially against Haemophilus influenza, have been available for some years with acknowledged efficacy. Now, the vaccine against Streptococcus pneumoniae (heptavalent vaccine) leads to a new perspective towards the management of respiratory diseases in children. In risk populations, the control of viral diseases through immunization, actively against the influenza virus and passively against the syncytial respiratory virus, is also an efficient measure to reduce respiratory disease.J Pediatr (Rio J) 2002; 78 (Supl.2) IntroduçãoÉ de todos conhecida a importância dos problemas infecciosos virais e bacterianos que acometem as vias aéreas superior e inferior. Sã...

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“…Large studies have shown that a pneumococcal conjugate vaccine is immunogenic and reduces invasive disease in infants and children. [33][34][35] …”

Section: Discussionmentioning

confidence: 99%

Carriage of antibiotic-resistant pneumococci in a cohort of a daycare center

Gómez-Barreto¹,

Calderón-Jaimes²,

Rodrı́guez³

et al. 2002

Salud pública Méx

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ResumenObjetivo. Analizar longitudinalmente la dinámica de colonización por Streptococcus pneumoniae, determinar la prevalencia, los factores de riesgo potencial para la colonización nasofaríngea con cepas de neumococo resistentes, determinar los serotipos y el perfil de sensibilidad a varios fár-macos antimicrobianos. Material y métodos. Estudio prospectivo de una cohorte de niños de guardería, hecho de septiembre de 1997 a septiembre de 1999 entre 53 niños asistentes a la guardería del Hospital Infantil de México Federico Gómez, atendida por 20 empleados. Todos los participantes fueron seguidos en forma prospectiva, tomándose exudado nasofaríngeo cada cuatro meses. Los S. pneumoniae aislados se tipificaron y sometieron a pruebas de sensibilidad a diversos fármacos. Las razones de momios y la prueba exacta de Fisher o ji cuadrada se efectuaron a través de tablas de contingencia; se utilizaron intervalos de confianza a 95% para las razones de momios. Para el análisis se empleó el programa estadístico EPI INFO, versión 6.04 a. Resultados. S. pneumoniae se recuperó de 45/53 niños en una o más de las tomas. Se aisló un total de 178 cepas. El promedio de portador fue de 47%. Sólo siete adultos adquirieron un neumococo durante el estudio. Los tipos 6, 14, 19 y 23 representaron 77% del total. Se encontró elevada resistencia a la penicilina y eritromicina. Conclusiones. El estado de portador nasofaríngeo de S. pneumoniae, es un proceso dinámico. La colonización ocurre durante los primeros meses de vida y comprende solamente unos cuantos serotipos de neumococo. El estado portador disminuye conforme avanza la edad. Se encontró alta proporción de portadores con cepas resistentes de neumococo. Los niños que recibieron varios cursos de antimicrobianos, fueron Patients were enrolled in the study during a two-year period from September 1997 to September 1999. All the participants were followed prospectively, swabbing them every four months. The strains recovered were typed and screened for susceptibility to several antibiotics. The daycare records were reviewed also. Odds ratios and fisher's exact test: or chi square test of significance were computed from contingency tables as appropriate. Exact 95% confidence intervals were computed for odds ratios. Data analysis was performed using Epi statistics program version 6.04 a.Results. Pneumococci were recovered from 45/53 of the infants at one or more visits. A total of 178 isolates were carried. The carriage rate was 47%. Only 7 adults acquired pneumococci during the study. Types 6,14,19 and 23 were prevalent and represented 77% of the total. Antibioticresistant strains were higher to penicillin and erythromycin. Conclusions. Children were frequent carriers of pneumococci, the rate of carriage was high in infancy and tended to decrease with age. The types commonly carried by children were the same as those causing invasive disease. There is a high proportion of carriers with antibiotic-resistant S. pneumoniae strains. Children who have had frequent antimicrobial courses are at p...

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Safety and Immunogenicity of Heptavalent Pneumococcal Vaccine Conjugated to CRM197 in United States Infants

Cited by 358 publications

References 19 publications

Vaccination against encapsulated bacteria in humans: paradoxes

Vaccination against encapsulated bacteria in humans: paradoxes

Vacinas e o trato respiratório: o que devemos saber?

Carriage of antibiotic-resistant pneumococci in a cohort of a daycare center

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