DNA vaccine encoding human immunodeficiency virus-1 Gag, targeted to the major histocompatibility complex II compartment by lysosomal-associated membrane protein, elicits enhanced long-term memory response

Antigen presentation by major histocompatibility complex type II (MHC II) molecules and activation of CD4+ helper T cells are critical for the generation of immunological memory. We previously described a DNA vaccine encoding human immunodeficiency virus-1 p55Gag as a chimera with the lysosome-associated membrane protein (LAMP/gag). The LAMP/gag chimera protein traffics to the MHC II compartment of transfected cells and elicits enhanced immune responses as compared to a DNA vaccine encoding native gag not targeted to the MHC II compartment. We have now investigated the long-term responses of immunized mice and show that the LAMP/gag DNA vaccine promotes long-lasting B cell- and CD4+ and CD8+ T-cell memory responses induced by DNA encoding non-targeted Gag decay rapidly and elicit very low or undetectable levels of gag DNA is sufficient to generate T-cell memory. Following this initial priming immunization with LAMP/gag DNA, booster immunizations with native gag DNA or the LAMP/gag chimera are equally efficient in eliciting B- and T-cell secondary responses, results in accordance with observations that secondary expansion of CD8+ cells in the boost phase does not require additional CD4+ help. These findings underscore the significance of targeting DNA-encoded vaccine antigens to the MHC II processing compartments for induction of long-term immunological memory.     

The geographic distribution of un-immunized children in Ontario,Canada: Hotspot detection using Bayesian spatial analysis

BackgroundIn Ontario, Canada, little is currently known about the extent to which un-immunized children may cluster geographically. Our objectives were to: describe the geographic distribution of fully un-immunized children; identify geographic clusters (hotspots) of un-immunized children; and to characterize the contribution of spatial effects and covariates on hotspots, where found.MethodsOur analytic cohort consisted of Ontario students aged 7–17 years in the 2016–2017 school year. We defined students as un-immunized if they had zero doses of any vaccine and a non-medical exemption recorded in Ontario’s registry. We calculated unadjusted proportions of un-immunized students by Census Subdivision (CSD) and then used a sequential approach to identify hotspots starting first with hotspot identification at the CSD level and then probed identified hotspots further by Dissemination Area (DA) and including covariates. Hotspots were identified using the Besag-York-Mollie Bayesian spatial model and were defined as areas with >95% probability of having two times the proportion of un-immunized students, relative to the province overall.ResultsWe identified 15,208 (0.94%) un-immunized children within our cohort consisting of more than 1.61 million students. Unadjusted proportions of un-immunized students varied greatly by geography, ranging from 0% to 21.5% by CSD. We identified 16 hotspot CSDs which clustered in five distinct areas, all of which were located in southern Ontario. The contribution of covariates and spatial effects on the risk of having un-immunized students varied greatly across hotspot areas.ConclusionsAlthough the provincial proportion (0.94%) of un-immunized students is small, geographical clustering of such students is evident in Ontario and in some areas presents an important risk for future outbreaks. Further qualitative work within these hotspot areas would be a helpful next step to better characterize the factors associated with vaccine refusal in these communities.     

Inactivated influenza virions are a flexible vaccine platform for eliciting protective antibody responses against neuraminidase

Most seasonal influenza vaccines are produced using hemagglutinin (HA) surface antigens from inactivated virions. However, virions are thought to be a suboptimal source for the less abundant neuraminidase (NA) surface antigen, which is also protective against severe disease. Here, we demonstrate that inactivated influenza virions are compatible with two modern approaches for improving protective antibody responses against NA. Using a DBA/2J mouse model, we show that the strong infection-induced NA inhibitory (NAI) antibody responses are only achieved by high dose immunizations of inactivated virions, likely due to the low viral NA content. Based on this observation, we first produced virions with higher NA content by using reverse genetics to exchange the viral internal gene segments. Single immunizations with these inactivated virions showed enhanced NAI antibody responses and improved NA-based protection from a lethal viral challenge while also allowing for the development of natural immunity to the heterotypic challenge virus HA. Second, we combined inactivated virions with recombinant NA protein antigens. These combination vaccines increased NA-based protection following viral challenge and elicited stronger antibody responses against NA than either component alone, especially when the NAs possessed similar antigenicity. Together, these results indicate that inactivated virions are a flexible platform that can be easily combined with protein-based vaccines to improve protective antibody responses against influenza antigens.     

Frequency and erroneous usage of temporary medical exemptions and knowledge of immunization guidelines among some Miami-Dade County Florida providers

Objective

We assessed knowledge and practices regarding immunization guidelines and the Florida Certificate of Immunization (DH-680) based on FL-DOH and CDC recommendations, to identify the cause of the increasing number of erroneously issued temporary medical exemptions (TME) among selected health care providers in Miami-Dade County Florida.

Methodology

After reviewing immunization certificates from all public schools, a list of physicians who improperly issued 3 or more TMEs, defined as one given to a child who was up to date for their kindergarten and seventh grade requirements, was compiled. The DOH-Miami-Dade developed educational materials and questionnaires, and conducted face-to-face interviews and interventions during site visits to these providers (n = 134). Data was analyzed using SAS 9.2.

Results

Of the 104 questionnaires completed, 4 (3.85%) had correct answers to all 10 vaccine knowledge and practice related questions, while 10 (9.62%) had 7 or more incorrect answers. Frequently missed questions included: the required doses of varicella vaccine for seventh grade students entering the 2011–12 school year (86, 82.7%) and the proper scenario for issuing a TME (57, 54.8%).

Conclusions

In order to eliminate the improper use of TMEs, long-term efforts are needed to provide immunization-related educational materials and trainings to the medical community regarding vaccinations. These findings also suggest a need for enhanced explanation in multiple languages on the current Florida Immunization Certificate. Due to enhanced surveillance and education, the number of TMEs for kindergarten and seventh grade students was reduced by 12% and 4.9%, respectively, during the 2011 and 2012 school year.     

Provider Attitudes Toward Public-Private Collaboration to Improve Immunization Reminder/Recall: A Mixed-Methods Study

ObjectiveTo assess primary care providers' current reminder/recall practices, preferences for collaboration with health departments in reminder/recall efforts, attitudes toward practice-based and population-based reminder/recall, and experiences with a population-based reminder/recall intervention.MethodsProviders responsible for making decisions about immunization delivery at all primary care practices that participate in the Colorado Immunization Information System were surveyed. Data collection was preceded by an intervention in which half of 14 counties received a population-based reminder/recall intervention conducted by the health department. Practice staff involved in immunization activities were then selected for semistructured telephone interviews that were based on the location of their practice within specified strata, including whether they were in the intervention counties, urban/rural location, and practice type.ResultsA total of 282 (73.6%) of 383 of providers responded to the survey, and 253 who administered vaccines to children 19 to 35 months were retained; 82 staff members at 36 practices were interviewed. Providers' preferences for who should conduct reminder/recall were almost evenly split, with slightly more indicating that it should be conducted by the health department. Cost and feasibility issues were perceived barriers to conducting practice-based recall, particularly among urban practices. Support for population-based reminder/recall was highest among rural practices. Concern about perceived inaccuracies in immunization registry data was the major barrier to conducting population-based reminder/recall. The population-based intervention did not create an undue burden on practices.ConclusionsA collaborative approach to reminder/recall involving both providers and health departments is preferable for many providers and may be a viable solution to the barriers of practice-based reminder/recall.     

Education in Quality Improvement for Pediatric Practice: An Online Program to Teach Clinicians QI

BackgroundEducation in Quality Improvement for Pediatric Practice (EQIPP) is an online program designed to improve evidence-based care delivery by teaching front-line clinicians quality improvement (QI) skills. Our objective was to evaluate EQIPP data to characterize 1) participant enrollment, use patterns, and demographics; 2) changes in performance in clinical QI measures from baseline to follow-up measurement; and 3) participant experience.MethodsWe conducted an observational study of EQIPP participants utilizing 1 of 3 modules (asthma, immunizations, gastroesophageal reflux disease) from 2009 to 2013. Enrollment and use, demographic, and quality measure data were extracted directly from the EQIPP system; participant experience was assessed via an optional online survey.ResultsStudy participants (n = 3501) were diverse in their gender, age, and race; most were board certified. Significant quality gaps were observed across many of the quality measures at baseline; sizable improvements were observed across most quality measures at follow-up. Participants were generally satisfied with their experience. The most influential module elements were collecting and analyzing data, creating and implementing aim statements and improvement plans, and completing “QI Basics.”ConclusionsOnline educational programs, such as EQIPP, hold promise for front-line clinicians to learn QI. The sustainability of the observed improvements in care processes and their linkage to improvements in health outcomes are unknown and are an essential topic for future study.     

Immunization of pediatric solid-organ transplantation candidates: immunizations in transplant candidates

Many children who receive solid-organ transplants have not completed their primary immunizations prior to transplantation. This leaves pediatric transplant recipients susceptible to the vaccine preventable illness of childhood, which if acquired post-transplantation are associated with increased rates of complications, hospitalization, graft rejection and mortality. The administration of vaccines to transplant candidates earlier and more rapidly than in the healthy child will improve vaccination rates among transplant recipients while not compromising immunogenicity. The recommended vaccines and vaccine schedule are discussed in detail.     

Immunization Needs of Chronic Liver Disease Patients Seen in Primary Care Versus Specialist Settings

Chronic liver disease patients may benefit from certain vaccines, but their immunization coverage levels have not been widely studied. We examined the serologic and vaccination status of 693 chronic liver disease patients from 37 primary care and specialist centers. Patients in primary care had more often received influenza (47 versus 32%; P < .001) and pneumococcal (39 versus 19%; P < .001) vaccines. Among patients without documented prior exposure, those seeing specialists had more often completed hepatitis A (28 versus 5%; P < .001) and hepatitis B (29 versus 14%; P < .001) vaccination. Coverage was higher in centers with a policy of vaccinating on-site, among non-Hispanic whites, and among patients with hepatitis C and cirrhosis. In summary, most patients were unprotected against one or more vaccine preventable diseases. The higher coverage rates evident in centers vaccinating on-site suggests a breakdown may occur when patients are referred to alternative vaccination venues.