Jacobson, Robert M.

ABSTRACT Interindividual variations in vaccine-induced immune responses are in part due to host genetic polymorphisms in the human leukocyte antigen (HLA) and other gene families. This study examined associations between HLA genotypes, haplotypes, and homozygosity and protective antigen (PA)-specific cellular immune responses in healthy subjects following immunization with Anthrax Vaccine Adsorbed (AVA). While limited associations were observed between individual HLA alleles or haplotypes and variable lymphocyte proliferative (LP) responses to AVA, analyses of homozygosity supported the hypothesis of a “heterozygote advantage.” Individuals who were homozygous for any HLA locus demonstrated significantly lower PA-specific LP than subjects who were heterozygous at all eight loci (median stimulation indices [SI], 1.84 versus 2.95, P = 0.009). Similarly, we found that class I (HLA-A) and class II (HLA-DQA1 and HLA-DQB1) homozygosity was significantly associated with an overall decrease in LP compared with heterozygosity at those three loci. Specifically, individuals who were homozygous at these loci had significantly lower PA-specific LP than subjects heterozygous for HLA-A (median SI, 1.48 versus 2.13, P = 0.005), HLA-DQA1 (median SI, 1.75 versus 2.11, P = 0.007), and HLA-DQB1 (median SI, 1.48 versus 2.13, P = 0.002) loci, respectively. Finally, homozygosity at an increasing number (≥4) of HLA loci was significantly correlated with a reduction in LP response ( P < 0.001) in a dose-dependent manner. Additional studies are needed to reproduce these findings and determine whether HLA-heterozygous individuals generate stronger cellular immune response to other virulence factors ( Bacillus anthracis LF and EF) than HLA-homozygous subjects.

OBJECTIVE: To determine the reasons adolescents are not vaccinated for specific vaccines and how these reasons have changed over time. METHODS: We analyzed the 2008–2010 National Immunization Survey of Teens examining reasons parents do not have their teens immunized. Parents whose teens were not up to date (Not-UTD) for Tdap/Td and MCV4 were asked the main reason they were not vaccinated. Parents of female teens Not-UTD for human papillomavirus vaccine (HPV) were asked their intent to give HPV, and those unlikely to get HPV were asked the main reason why not. RESULTS: The most frequent reasons for not vaccinating were the same for Tdap/Td and MCV4, including “Not recommended” and “Not needed or not necessary.” For HPV, the most frequent reasons included those for the other vaccines as well as 4 others, including “Not sexually active” and “Safety concerns/Side effects.” “Safety concerns/Side effects” increased from 4.5% in 2008 to 7.7% in 2009 to 16.4% in 2010 and, in 2010, approaching the most common reason “Not Needed or Not Necessary” at 17.4% (95% CI: 15.7–19.1). Although parents report that health care professionals increasingly recommend all vaccines, including HPV, the intent to not vaccinate for HPV increased from 39.8% in 2008 to 43.9% in 2010 (OR for trend 1.08, 95% CI: 1.04–1.13). CONCLUSIONS: Despite doctors increasingly recommending adolescent vaccines, parents increasingly intend not to vaccinate female teens with HPV. The concern about safety of HPV grew with each year. Addressing specific and growing parental concerns about HPV will require different considerations than those for the other vaccines.

Abstract In this article we define vaccinomics as the integration of immunogenetics and immunogenomics with systems biology and immune profiling. Vaccinomics is based on the use of cutting edge, high-dimensional (so called “omics”) assays and novel bioinformatics approaches to the development of next-generation vaccines and the expansion of our capabilities in individualized medicine. Vaccinomics will allow us to move beyond the empiric “isolate, inactivate, and inject” approach characterizing past vaccine development efforts, and toward a more detailed molecular and systemic understanding of the carefully choreographed series of biological processes involved in developing viral vaccine-induced “immunity.” This enhanced understanding will then be applied to overcome the obstacles to the creation of effective vaccines to protect against pathogens, particularly hypervariable viruses, with the greatest current impact on public health. Here we provide an overview of how vaccinomics will inform vaccine science, the development of new vaccines and/or clinically relevant biomarkers or surrogates of protection, vaccine response heterogeneity, and our understanding of immunosenescence.

Despite improvements in clinician education, symptom awareness, and respiratory precautions, influenza vaccination rates for health care workers have remained unacceptably low for more than three decades, adversely affecting patient safety. When public health is jeopardized, and a safe, low-cost, and effective method to achieve patient safety exists, health care organizations and public health authorities have a responsibility to take action and change the status quo. Mandatory influenza vaccination for health care workers is supported not only by scientific data but also by ethical principles and legal precedent. The recent influenza pandemic provides an opportunity for policymakers to reconsider the benefits of mandating influenza vaccination for health care workers, including building public trust, enhancing patient safety, and strengthening the health care workforce.