Cellular immunity to vaccines is highly variable during infancy. This study addressed the hypothesis that these responses are governed by the pace of maturational changes in adaptive immune competence, in particular, cellular functions that underlie the postnatal transition from Th2 to Th1 "bias." Tetanus-specific cytokine responses were tracked in peripheral blood mononuclear cells collected from infants at months 2, 4, 6, 12, and 18. These were compared with polyclonal responses. Results show that the Th2 component of the vaccine response develops rapidly and remains stable, unlike interferon (IFN)-gamma production, which also is initiated early but commonly declines after the final priming dose at 6 months. However, between 12 and 18 months, the IFN-gamma component of the vaccine-specific response has a spontaneous resurgence that coincides with a parallel increase in overall IFN-gamma production capacity. The Th2 component of vaccine-specific responses was more prominent in children with atopic family history.
Immune responses to exogenous antigens in infant experimental animals display various degrees of Th2 polarization. Preliminary evidence from small human studies suggest a similar age-dependent response pattern to vaccines, but detailed investigations on vaccine immunity during infancy have not yet been undertaken. We report below the results of a comprehensive prospective study on responses to the tetanus component of the diphtheria, tetanus, acellular pertussis (DTaP) vaccine in a cohort of 55 healthy children, employing peripheral blood mononuclear cells (PBMC) collected at the 2-, 4-, and 6-month vaccinations and at 12 months. Antigen-specific production of interleukin-4 (IL-4), IL-5, IL-6, IL-9, IL-10, IL-13, and gamma interferon (IFN-␥) was determined at each sample point, in parallel with polyclonal (phytohemagglutinin PHA-induced) cytokine responses. Our results indicate early and persistent Th2 responses to the vaccine, in contrast to a more delayed and transient pattern of IFN-␥ production. This initial disparity between the Th1 and Th2 components of the vaccine response was mirrored by patterns of polyclonally induced cytokine production, suggesting that the delayed maturation of the Th1 component of the vaccine response during infancy is secondary to developmental processes occurring within the overall Th cell system.The current schedule for vaccination of infants with the diphtheria, tetanus, acellular pertussis (DTaP) vaccine is the subject of increasing debate, in particular the relationship between the timing and frequency of dosing and the subsequent generation of immunological memory. The nature of the response to the initial cycle of three primary vaccinations given during infancy represents the least understood aspect of this question. Although systematic kinetic studies have been conducted on antibody responses, studies of cellular responses in large samples of subjects over this age range have not yet been performed.Of particular interest in this context are vaccine antigenspecific T-helper (Th)-cell cytokine responses during early infancy. It is evident from a number of clinical efficacy trials focusing on the pertussis component of the vaccine that protection against infection does not correlate consistently with specific serum antibody titer (1,8,11,12,22,24). This argues that other aspects of the host response (notably cellular immunity) may also be important in the defense against infection, and this conclusion is reinforced by results from animal model systems which demonstrate a key role for cytokine-secreting CD4 ϩ T cells, in particular T cells secreting Th1 cytokines, in protection against respiratory tract challenge with pertussis (15,17). Similarly, in terms of adult responses to tetanus toxoid (TT), both Th1 and Th2 cytokines have been implicated in vaccine-induced protection (9, 10).However, recent studies in mice (6,20,23), and also in humans (reviewed in reference 13) suggest that the capacity to generate both acute and persistent Th1 responses to antigen challenge during the...
Summary Background On April 25, 2017, a cluster of unexplained illnesses and deaths associated with a funeral was reported in Sinoe County, Liberia. Molecular testing identified Neisseria meningitidis serogroup C (NmC) in specimens from patients. We describe the epidemiological investigation of this cluster and metagenomic characterisation of the outbreak strain. Methods We collected epidemiological data from the field investigation and medical records review. Confirmed, probable, and suspected cases were defined on the basis of molecular testing and signs or symptoms of meningococcal disease. Metagenomic sequences from patient specimens were compared with 141 meningococcal isolate genomes to determine strain lineage. Findings 28 meningococcal disease cases were identified, with dates of symptom onset from April 21 to April 30, 2017: 13 confirmed, three probable, and 12 suspected. 13 patients died. Six (21%) patients reported fever and 23 (82%) reported gastrointestinal symptoms. The attack rate for confirmed and probable cases among funeral attendees was 10%. Metagenomic sequences from six patient specimens were similar to a sequence type (ST) 10217 (clonal complex [CC] 10217) isolate genome from Niger, 2015. Multilocus sequencing identified five of seven alleles from one specimen that matched ST-9367, which is represented in the PubMLST database by one carriage isolate from Burkina Faso, in 2011, and belongs to CC10217. Interpretation This outbreak featured high attack and case fatality rates. Clinical presentation was broadly consistent with previous meningococcal disease outbreaks, but predominance of gastrointestinal symptoms was unusual compared with previous African meningitis epidemics. The outbreak strain was genetically similar to NmC CC10217, which caused meningococcal disease outbreaks in Niger and Nigeria. CC10217 had previously been identified only in the African meningitis belt.
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