The Immunogenetics of Measles Immunity (NIAID/NIH)

To examine the role of gene polymorphisms (including functional studies of SNPs) on variations in vaccine-induced immune responses, in approximately 3,000 healthy school-age children, adolescents and young adults/adults, who were vaccinated with measles-containing vaccine (MMR). To achieve greatest power to detect SNPs associated with measles-specific immune response phenotypes, we pooled our data across three genotyping platforms and three cohorts (US cohort, San Diego cohort and Rochester cohort).]]>
Genome-wide associations of CD46 and IFI44L genetic variants with neutralizing antibody response to measles vaccineSupplementary MaterialsAnalysis Methods for Measles Residual GWASThe US routinely vaccinates children with two doses of MMR (measles, mumps, and rubella) with the intention of inducing lifelong immunity. Our study comprised three cohorts representing the US population vaccinated against measles with the attenuated live vaccine currently licensed for routine administration. The US and San Diego Cohorts represent US military personnel and offer geographical diversity as well as diversity in age, race, ethnicity, and gender. They also represent older adolescents and healthy adults 18 to 40 years of age who, because of their military status, have had their vaccine status interrogated and documented to assure immunity against measles. The Rochester Cohort represents schoolchildren, teens, and young adults 11 to 22 years of age who have received two doses of measles-containing vaccine and were old enough to have undergone the volume of blood sampling required for our studies. For all of our subjects we used electronic vaccine records to document their measles vaccination history. The US Cohort consists of approximately 1,000 human subjects who are 18 to 40 years old and in good health. We conducted enrollment of this cohort from April 2011 through October 2011 as part of our contract HHSN272201000025C entitled "Population Genetics Analysis Program." We originally recruited these individuals because they were active military personnel recently vaccinated with smallpox vaccine due to overseas deployment. As members of the US military, they represent a cross section of the US population with proven vaccine-induced immunity to measles. We used medical record documentation for everyone in the US Cohort to confirm their measles vaccine dates. We included subjects if they were willing to give informed consent, were in the age range of 18 through 40 years old, in good health, and whose medical conditions, if any, were stable -- where stable is defined as not requiring either a significant change in therapy or a hospitalization in the last 12 weeks. We excluded subjects who had a known or suspected immunodeficiency or received treatment with immunosuppressive therapy including cytotoxic agents or systemic corticosteroids (e.g., for cancer, HIV, or autoimmune disease); received systemic corticosteroids for treatment of an acute illness in the last 30 days; had a serious chronic disorder including metastatic malignancy, severe chronic obstructive pulmonary disease requiring supplemental oxygen, end stage renal disease with or without dialysis, clinically unstable cardiac disease, or any other disorder that in the investigators' opinion precludes the subject from participating in the study; or received any blood products, including immunoglobulin, within six months of study enrollment. In addition, the second dose must have been received one or more months after the first dose. The US Cohort offers us rich racial diversity and a broad age group of measles-vaccinated individuals. The San Diego Cohort consists of approximately 1,000 human subjects who are also 18 to 40 years old and in good health. We conducted enrollment of this cohort from July 2005 through September 2006 as part of our previous contract HHS3004000065C N01-AI40065 entitled, "Population Genetics Analysis Program." In this recruitment, unfortunately, our collaborators did not distinguish Asians from Native Hawaiian or Other Pacific Islanders and reported these two groups as one. Otherwise, we utilized the same inclusion and exclusion eligibility criteria as was used for the US Cohort. Just as with the US Cohort, we originally recruited these individuals because they were active military personnel recently vaccinated with smallpox vaccine due to overseas deployment. Again, as members of the US military, they represent a cross section of the US population with proven immunity to measles. The Rochester Cohort consists of approximately 1,000 human subjects who are 11 to 22 years old and in good health. We completed recruitment of these individuals for past NIH funded R01 grants specifically for candidate gene studies with respect to their measles and rubella immune status. These individuals were older school-age children, adolescents, and young adults at the time of their sampling. We recruited the individuals during three different periods in the last decade. The Rochester Cohort comprises three subcohorts with subjects already recruited and sampled for several NIH-funded grant applications, all of whom have documentation of two doses of MMR vaccination, as listed below: 1.) The first of these subcohorts came from our original NIH-funded grant application "Immunogenetic Mechanisms of Vaccine Response" (R01-AI48793) Years 1 through 5. For this application, we recruited 324 subjects 12 to 18 years of age from December 2001 through August 2002. 2.) The second subcohort came from our NIH-funded grant application "Immunogenetic Mechanisms of Vaccine Response" (R01-AI48793) Years 6 through 10. For this study, we recruited 440 volunteers from a random sample of 11- to 18-year-old children registered with the Rochester School District from December 2006 through August 2007. The third subcohort came from our NIH-funded grant application "The Immunogenetics of Measles Immunity" (R01-AI33144) Years 13 through 18. In this study, we recruited an additional 381 volunteers from a random sample of children 11 to 18 years of age registered with the Rochester School District, enriched with African-American youth 11 to 22 years of age who otherwise meet the same eligibility criteria. We conducted this wave of recruitment from November 2008 through September 2009. We included subjects if in the range of 11 through 22 years of age, in good health, having received two (and only two) doses of the MMR vaccine as a live viral vaccine licensed in the US. Furthermore, these subjects received their first dose at 12-59 months of age. They received their second dose at least one month after the first dose and before reaching the age of 13. They completed vaccination at least one month before sampling. We excluded subjects if they suffered from an immunocompromising condition at the time of sampling, vaccination, or at the time of enrollment in our studies. Subjects were ineligible if their histories were unknown or irretrievable-as might have been the case with adopted children, or if they had received a blood product at the time or within a timeframe such that the blood product might have interfered with the vaccine response by providing passive antibody. Subjects were also ineligible if they received less than or more than two full doses of the US licensed MMR vaccine. Evidence for Measles Vaccinethe receipt of the MMR vaccine required documentation of a complete, up-to-date vaccination record. We excluded children if a parent was unwilling to give permission, if the child was unwilling to assent or if, in the judgment of the investigator, the child should not participate in the study.]]>