Evaluation of potentially achievable vaccination coverage with simultaneous administration of vaccines among children in the United States

BackgroundRoutine administration of all age-appropriate doses of vaccines during the same visit is recommended for children by the National Vaccine Advisory Committee (NVAC) and the Advisory Committee on Immunization Practices (ACIP).MethodsEvaluate the potentially achievable vaccination coverage for ≥4 doses of diphtheria and tetanus toxoids and acellular pertussis vaccine (4+DTaP), ≥4 doses of pneumococcal conjugate vaccine (4+PCV), and the full series of Haemophilus influenzae type b vaccine (Hib-FS) with simultaneous administration of all recommended childhood vaccines. Compare the potentially achievable vaccination coverage to the reported vaccination coverage for calendar years 2001 through 2013; by state in the United States and by selected socio-demographic factors in 2013. The potentially achievable vaccination coverage was defined as the coverage possible for the recommended 4+DTaP, 4+PCV, and Hib-FS if missed opportunities for simultaneous administration of all age-appropriate doses of vaccines for children had been eliminated.ResultsCompared to the reported vaccination coverage, the potentially achievable vaccination coverage for 4+DTaP, 4+PCV, and Hib-FS could have increased significantly (P < 0.001), the vaccination coverage would have achieved the 90% target of Healthy People 2020 for the three vaccines beginning in 2005, 2008, and 2011 respectively. In 2013, the potentially achievable vaccination coverage increased significantly across all selected socio-demographic factors, potentially achievable vaccination coverage would have reached the 90% target for more than 51% of the states in the United States.ConclusionsThe findings in this study suggest that fully utilization of all opportunities for simultaneous administration of all age-eligible childhood doses of vaccines during the same vaccination visit is a critical strategy for achieving the vaccination coverage target of Healthy People 2020. Encouraging providers to deliver all recommended vaccines that are due at each visit by implementing client reminder and recall systems might decrease missed opportunities for simultaneous administration of childhood vaccines.     

A comparison of different vaccination schemes used in sheep combining inactivated bluetongue vaccines against serotypes 4 and 8

Eight different vaccination schemes using four commercially available inactivated Bluetongue vaccines against serotypes 4 and 8 in three different combinations (setting 1–3) were tested under field conditions for their ability to generate a measurable immune response in sheep.Animals of setting 1 (groups A–D) were simultaneously vaccinated using either individual injections at different locations (groups A & D) or double injection by a twin-syringe (groups B & C). For both application methods, a one-shot vaccination (groups C & D) was compared to a boosted vaccination (groups A & B). Sheep of setting 2 (groups E–G) were vaccinated in an alternating, boosted pattern at fortnightly intervals starting with serotype 4 (groups E & F) or vice versa (group G). Group H of setting 3 was vaccinated simultaneously and vaccines were injected individually as a one-shot application. Each group consisted of 30 sheep. The immunogenic response was tested in all sheep (n = 240) by ELISA (IDScreen®Bluetongue Competition), while serum neutralisation tests were performed in five to six sheep from each group (n = 45).All vaccine combinations were well tolerated by all sheep. Of all vaccines and schemes described, the simultaneous double injected boosted vaccination of setting 1 (group B) yielded the highest median serotype-specific titres 26 weeks after the first vaccination (afv) and 100% seropositive animals (ELISA) one year afv. In setting 1, there were no relevant significant differences in the immunogenic response between simultaneously applied vaccines at different sites or at the same injection site. Importantly, a one-shot vaccination induced comparable immunogenicity to a boosted injection half a year afv. Low serotype-specific neutralising antibody levels were detected in settings 2 and 3 and are attributed to diverse factors which may have influenced the measured immunogenicity.     

Immunogenicity of a recombinant fusion construct composed of intrinsically unstructured,low polymorphic segments derived from merozoite surface protein 2 and trophozoite exported protein 1

To overcome the extensive polymorphism found in human Plasmodium antigens and to avoid the lengthy characterization of their 3 dimensional structure and subsequent production of the native proteins we have been concentrated in large unstructured, non-or low-polymorphic fragments present in the blood stage of P. falciparum. Three fragments derived from the 2 family-specific and constant regions of merozoite surface protein (MSP2) and PFF0165c protein were previously selected for evaluation as potential single vaccine candidates. In order to increase and optimize their potential efficacy against P. falciparum infection the 3 antigens were combined in a single DNA recombinant product (FusN) and compared its antigenicity with that of single antigens in sera of volunteers living in endemic countries. Immunogenicity of the FusN was then compared with that of the mixture of 3 antigens in 3 strains of mice. Antigen specific, affinity purified human antibodies were then tested in antibody dependent cellular inhibition and merozoite opsonization assays. In addition, the antigen specific antibody response and its association with protection from malaria infection were determined. The data collected indicate that the recombinant product is an equal or better antigen /immunogen than fragments used either alone or as a mixture for vaccination in combination with adjuvant. In addition, antibody response to FusN shows a stronger association with protection than single fragments. The use of a single construct as vaccine would drastically reduce the cost of manufacturing and development of the GMP product.     

Unique safety issues associated with virus-vectored vaccines: Potential for and theoretical consequences of recombination with wild type virus strains

In 2003 and 2013, the World Health Organization convened informal consultations on characterization and quality aspects of vaccines based on live virus vectors. In the resulting reports, one of several issues raised for future study was the potential for recombination of virus-vectored vaccines with wild type pathogenic virus strains. This paper presents an assessment of this issue formulated by the Brighton Collaboration.To provide an appropriate context for understanding the potential for recombination of virus-vectored vaccines, we review briefly the current status of virus-vectored vaccines, mechanisms of recombination between viruses, experience with recombination involving live attenuated vaccines in the field, and concerns raised previously in the literature regarding recombination of virus-vectored vaccines with wild type virus strains. We then present a discussion of the major variables that could influence recombination between a virus-vectored vaccine and circulating wild type virus and the consequences of such recombination, including intrinsic recombination properties of the parent virus used as a vector; sequence relatedness of vector and wild virus; virus host range, pathogenesis and transmission; replication competency of vector in target host; mechanism of vector attenuation; additional factors potentially affecting virulence; and circulation of multiple recombinant vectors in the same target population. Finally, we present some guiding principles for vector design and testing intended to anticipate and mitigate the potential for and consequences of recombination of virus-vectored vaccines with wild type pathogenic virus strains.     

Burden of invasive pneumococcal disease (IPD) in Sri-Lanka: Deriving a reasonable measure for vaccine introduction decision making

PurposeThe lack of evidence on the disease burden has been an obstacle for decision-making on introducing pneumococcal vaccines in Sri-Lanka. Hence, the purpose of this study is to determine the incidence of invasive pneumococcal disease among children under five-years of age in Sri-Lanka's Colombo district.MethodsIn a community-based study, using a sample of 2310 children, we identified syndromes associated with pneumococcal disease (pneumonia, meningitis, sepsis). The estimates of annual cumulative incidence of invasive pneumococcal disease were derived by having applied proportions of laboratory confirmed invasive pneumococcal disease among all-cause syndromes associated with pneumococcal infection obtained from the hospital-based invasive bacterial disease sentinel surveillance and findings of the community-based study to population parameters of the district. The estimates of invasive pneumococcal pneumonia and sepsis based on low-sensitive, culture confirmation were adjusted by a correction factor.ResultsThe annual cumulative incidence of all-cause clinical syndromes associated with pneumococcal disease (pneumonia, meningitis, sepsis) were 1.3, 0.52, 0.39 per 100 children, respectively. The estimate of adjusted, invasive pneumococcal disease cumulative incidence was 206.3 per 100,000 while estimates of pneumococcal pneumonia, meningitis and sepsis cumulative incidence were 147.9, 13.2 and 45.2 per 100,000 under-five children.ConclusionReasonable estimates of invasive pneumococcal disease could be derived by using incidence of clinical syndromes associated with pneumococcal disease obtained from population-based studies and proportion of pneumococcal infection among all-cause clinical syndromes associated with pneumococcal disease generated from hospital-based sentinel surveillance. These estimates may help informed decision-making on introduction of pneumococcal conjugated vaccine.