Immune response at 12-23 months following a single dose of Vero cell culture-derived Japanese encephalitis (JE) vaccine in adults previously vaccinated with mouse brain-derived JE vaccine.

BACKGROUND: Japanese encephalitis (JE) virus is an important cause of neurological disease in Asia. JE vaccine is recommended for travelers with higher JE risk itineraries. Inactivated Vero cell culture-derived JE vaccine (JE-VC) is the only JE vaccine currently available in the United States. An inactivated mouse brain-derived JE vaccine (JE-MB) previously was available but production was discontinued. One JE-VC dose administered to adults previously vaccinated with ≥3 doses of JE-MB provides good short-term protection for at least one month, but data on longer-term protection are limited. We evaluated non-inferiority of the JE virus neutralizing antibody response at 12-23 months in JE-MB-vaccinated adults administered one JE-VC dose compared with JE vaccine-naïve adults administered a JE-VC two-dose primary series. METHODS: We obtained archived sera from U.S. military personnel and performed a 50% plaque reduction neutralization test for anti-JE virus neutralizing antibodies. We compared the geometric mean titer (GMT) and seroprotection rate at 12-23 months after one JE-VC dose in previously JE-MB-vaccinated personnel and after the second JE-VC dose in previously JE vaccine-naïve personnel. Non-inferiority was concluded if the lower bound of the two-sided 95% confidence interval (CI) of the GMT ratio in previously vaccinated to vaccine-naïve personnel was >1/1.5. RESULTS: The GMT in previously JE-MB-vaccinated persons was 75 (95% CI 63-90) and in previously JE vaccine-naïve persons was 12 (95% CI 11-14), and seroprotection rates were 94% (235/250) and 54% (135/250), respectively. The ratio of GMTs was 6.3 (95% CI: 5.0-7.7), satisfying the criterion for non-inferiority. CONCLUSIONS: One JE-VC dose in previously JE-MB-vaccinated military personnel provides good protection for at least 1-2 years. The benefits of administration of a single JE-VC dose in previously JE-MB-vaccinated adults include a shorter time to completion of re-vaccination before travel, a decrease in the risk of adverse events, and reduced costs.

Duration of seropositivity following yellow fever vaccination in U.S. military service members.

BACKGROUND: The United States military regularly deploys thousands of service members throughout areas of South America and Africa that are endemic for yellow fever (YF) virus. To determine if booster doses might be needed for service members who are repetitively or continually deployed to YF endemic areas, we evaluated seropositivity among US military personnel receiving a single dose of YF vaccine based on time post-vaccination. METHODS: Serum antibodies were measured using a plaque reduction neutralization test with 50% cutoff in 682 military personnel at 5-39 years post-vaccination. We determined noninferiority of immune response by comparing the proportion seropositive among those vaccinated 10-14 years previously with those vaccinated 5-9 years previously. Noninferiority was supported if the lower-bound of the 2-tailed 95% CI for p10-14years - p5-9years was ≥-0.10. Additionally, the geometric mean antibody titer (GMT) at various timepoints following vaccination were compared to the GMT at 5-9 years. RESULTS: The proportion of military service members with detectable neutralizing antibodies 10-14 years after a single dose of YF vaccine (95.8%, 95% CI 91.2-98.1%) was non-inferior to the proportion 5-9 years after vaccination (97.8%, 95% CI 93.7-99.3%). Additionally, GMT among vaccine recipients at 10-14 years post vaccination (99, 95% CI 82-121) was non-inferior to GMT in YF vaccine recipients at 5-9 years post vaccination (115, 95% CI 96-139). The proportion of vaccinees with neutralizing antibodies remained high, and non-inferior, among those vaccinated 15-19 years prior (98.5%, 95%CI 95.5-99.7%). Although the proportion seropositive decreased among vaccinees ≥ 20 years post vaccination, >90% remained seropositive. CONCLUSIONS: Neutralizing antibodies were present in > 95% of vaccine recipients for at least 19 years after vaccination, suggesting that booster doses every 10 years are not essential for most U.S. military personnel.

Prospective safety surveillance study of ACAM2000 smallpox vaccine in deploying military personnel.

OBJECTIVES: To compare rates of myopericarditis, severe and serious dermatological or neurological events, and other adverse events in deploying US military personnel who received or did not receive ACAM2000® (Smallpox [Vaccinia] Vaccine, Live) vaccine and to evaluate potential risk factors for development of myopericarditis. METHODS: Prospective observational cohort study enrolling up to 15,000 ACAM2000 recipients (Cohort 1) and up to 5000 persons otherwise eligible for ACAM2000 vaccination but not vaccinated due to recency of vaccination or characteristics of their contacts (Cohort 2). Data and specimens were collected initially and 10 (6-17) days later. Those with clinical or laboratory evidence of possible myopericarditis were referred for further evaluation and adjudication by a blinded independent review committee. The adjusted odds ratio for myopericarditis was determined by a logistic regression model controlling for age, race, gender, and exercise regimen. RESULTS: 14,667 subjects provided initial data and specimens (Cohort 1, 10,825; Cohort 2, 3842); 12,110 (Cohort 1, 8945; Cohort 2, 3165) completed Visit 2 per-protocol. A total of 125 (Cohort 1, 111; Cohort 2, 14) were referred for myopericarditis adjudication, yielding 54 (Cohort 1, 44, Cohort 2, 10) subclinical myopericarditis, 5 suspected myocarditis, 1 confirmed myocarditis, and 1 suspected pericarditis. Unadjusted myopericarditis rates were: Cohort 1, 5.7/1000 (95% CI, 4.3-7.5); Cohort 2, 3.2/1000 (95% CI, 1.7-5.8). Unadjusted and adjusted odds ratios for myopericarditis were 1.8 (95% CI: 0.9-3.6) and 1.3 (95% CI: 0.6-2.6), respectively. One hundred seventeen subjects (1.1%) in Cohort 1 and 13 (0.3%) in Cohort 2 experienced at least 1 serious adverse event. No instances of serious and severe neurological or dermatological adverse events were reported. CONCLUSIONS: In this carefully screened, generally young and healthy service-member population, ACAM2000 vaccination was associated with modest non-significant increases in the risk of myopericarditis (adjusted OR, 1.3; unadjusted OR, 1.8); all but seven cases were subclinical. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT00928577.

Morning Cortisol Is Associated With Stress and Sleep in Elite Military Men: A Brief Report.

INTRODUCTION: Accumulating evidence suggests that trends in salivary cortisol after awakening may be reliable biological predictors of morbidity and mortality. In a sample of elite military men, our lab recently established summary parameters of morning cortisol as well as their stability across 2 d of repeated sampling. MATERIALS AND METHODS: In this follow-on study, we evaluated summary parameters and their relationships to theoretically relevant demographic (i.e., age, body mass index) and biobehavioral correlates (i.e., blood pressure [BP], sleep parameters, fatigue, and perceived stress). Fifty-eight male active duty U.S. Navy SEALs self-collected salivary samples on 2 consecutive, midweek workdays upon waking (WAKE), WAKE+30 min, WAKE+60 min, 4 p.m., and 9 p.m. in a nondeployed, free-living setting. Resting BP was measured manually, and sleep-wake periods were objectively derived using actigraphy. Daily fatigue and perceived stress were measured by self-report. Summary parameters of morning cortisol magnitude (i.e., peak value [Peak], area under the curve in terms of ground [AUCG], and average of morning samples [AVE]) were assessed with respect to each demographic and biobehavioral item via correlational analyses. A subgroup of 29 participants was selected for compliance with salivary sampling in the morning across 2 d. RESULTS: Perceived stress was positively associated with Peak (r[27] = 0.437, p < 0.05), AUCG (r[25] = 0.500, p < 0.01), and AVE (r[25] = 0.506, p < 0.01). Total sleep time was also positively associated with Peak (r[26] = 0.378, p < 0.05). There were borderline associations between some summary parameters and diastolic BP, percent sleep, and wake after sleep onset. Age, systolic BP, body mass index, time in bed, sleep efficiency, and fatigue did not associate with morning cortisol. CONCLUSIONS: Preliminary evidence of morning cortisol summary parameters as biobehavioral indicators was established, and these parameters appeared to associate with stress and sleep in elite military men.