Challenges in vaccination of neonates, infants and young children

Pichichero, Michael E.

doi:10.1016/j.vaccine.2014.05.008

Cited by 40 publications

(37 citation statements)

References 99 publications

(109 reference statements)

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“…The gradual development of microbiota may reflect the stepwise development of host physiology. For example, the most important cellular components of the gastrointestinal immune system are already present in fetal life (Tourneur and Chassin, 2013), but a newborn still has immature intestinal mucosal layer, immunological and metabolic functions (Fernandez et al, 2011;Jakobsson et al, 2014;Levy and Wynn, 2014;Pichichero, 2014). After a few months, infants are able to absorb fat-soluble compounds efficiently because of maturation of bile salt (Fernandez et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Discordant temporal development of bacterial phyla and the emergence of core in the fecal microbiota of young children

et al. 2015

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The colonization pattern of intestinal microbiota during childhood may impact health later in life, but children older than 1 year are poorly studied. We followed healthy children aged 1-4 years (n = 28) for up to 12 months, during which a synbiotic intervention and occasional antibiotics intake occurred, and compared them with adults from the same region. Microbiota was quantified with the HITChip phylogenetic microarray and analyzed with linear mixed effects model and other statistical approaches. Synbiotic administration increased the stability of Actinobacteria and antibiotics decreased Clostridium cluster XIVa abundance. Bacterial diversity did not increase in 1-to 5-year-old children and remained significantly lower than in adults. Actinobacteria, Bacilli and Clostridium cluster IV retained child-like abundances, whereas some other groups were converting to adult-like profiles. Microbiota stability increased, with Bacteroidetes being the main contributor. The common core of microbiota in children increased with age from 18 to 25 highly abundant genus-level taxa, including several butyrate-producing organisms, and developed toward an adult-like composition. In conclusion, intestinal microbiota is not established before 5 years of age and diversity, core microbiota and different taxa are still developing toward adult-type configuration. Discordant development patterns of bacterial phyla may reflect physiological development steps in children.

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Section: Discussionmentioning

confidence: 99%

Discordant temporal development of bacterial phyla and the emergence of core in the fecal microbiota of young children

et al. 2015

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“…Humans and mice have a less mature immune response during infancy than in adulthood (35)(36)(37)(38). Human infants will be a primary vulnerable population targeted for next-generation PPVs.…”

Section: Phtd Vaccination Prevents Pneumococcal Invasionmentioning

confidence: 99%

Protection against Streptococcus pneumoniae Invasive Pathogenesis by a Protein-Based Vaccine Is Achieved by Suppression of Nasopharyngeal Bacterial Density during Influenza A Virus Coinfection

Khan

Pichichero

2017

Infect Immun

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An increase in Streptococcus pneumoniae nasopharynx (NP) colonization density during a viral coinfection initiates pathogenesis. To mimic natural S. pneumoniae pathogenesis, we commensally colonized the NPs of adult C57BL/6 mice with S. pneumoniae serotype (ST) 6A or 8 and then coinfected them with mouseadapted H1N1 influenza A virus (PR/8/34). S. pneumoniae established effective commensal colonization, and influenza virus coinfection caused S. pneumoniae NP density to increase, resulting in bacteremia and mortality. We then studied histidine triad protein D (PhtD), an S. pneumoniae adhesin vaccine candidate, for its ability to prevent invasive S. pneumoniae disease in adult and infant mice. In adult mice, the efficacy of PhtD vaccination was compared with that of PCV13. Vaccination with PCV13 led to a greater reduction of S. pneumoniae NP density (Ͼ2.5 log units) than PhtD vaccination (ϳ1-log-unit reduction). However, no significant difference was observed with regard to the prevention of S. pneumoniae bacteremia, and there was no difference in mortality. Depletion of CD4 ϩ T cells in PhtD-vaccinated adult mice, but not PCV13-vaccinated mice, caused a loss of vaccine-induced protection. In infant mice, passive transfer of antisera or CD4 ϩ T cells from PhtD-vaccinated adult mice led to a nonsignificant reduction in NP colonization density, whereas passive transfer of antisera and CD4 ϩ T cells was needed to cause a significant reduction in NP colonization density. For the first time, these data show an outcome with regard to prevention of invasive S. pneumoniae pathogenesis with a protein vaccine similar to that which occurs with a glycoconjugate vaccine despite a less robust reduction in NP bacterial density.

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“…For example, recruitment of T cell help to B cells is hampered as a result of low MHC II and reduced antigen processing and presentation [11]. In addition, decreased dendritic cell maturation contributes to poor CD4 + T cell generation necessary to support antibody responses [4, 12, 13].…”

Section: Introductionmentioning

confidence: 99%

Adjuvanting an inactivated influenza vaccine with conjugated R848 improves the level of antibody present at 6 months in a nonhuman primate neonate model

Holbrook

D’Agostino

Aycock

et al. 2017

Vaccine

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Generation of a potent antibody response that can be sustained over time is highly challenging in young infants. Our previous studies using a nursery-reared nonhuman primate model identified R848 conjugated to inactivated influenza virus as a highly immunogenic vaccine for neonates. Here we determined the effectiveness of this vaccine in mother-reared infants as well as its ability to promote improved responses at 6 months compared to vaccination in the absence of R848. In agreement with our nursery study, R848 conjugated to influenza virus induced a higher antibody response in neonates compared to the non-adjuvanted vaccine. Further, the increase in the response relative to that induced by the non-adjuvanted vaccine was maintained at 6 months suggesting the increased antibody secreting cells that resulted from inclusion of conjugated R848 production were capable of surviving long term. There was no significant difference in quality of antibody (i.e. neutralization or affinity), suggesting the beneficial effect of conjugated R848 during vaccination of neonates with inactivated influenza virus is likely manifest during the early generation of antibody secreting cells.

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Challenges in vaccination of neonates, infants and young children

Cited by 40 publications

References 99 publications

Discordant temporal development of bacterial phyla and the emergence of core in the fecal microbiota of young children

Discordant temporal development of bacterial phyla and the emergence of core in the fecal microbiota of young children

Protection against Streptococcus pneumoniae Invasive Pathogenesis by a Protein-Based Vaccine Is Achieved by Suppression of Nasopharyngeal Bacterial Density during Influenza A Virus Coinfection

Adjuvanting an inactivated influenza vaccine with conjugated R848 improves the level of antibody present at 6 months in a nonhuman primate neonate model

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