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Introduction: Pandemic influenza vaccine development focuses on the hemagglutinin (HA) antigen for potency and immunogenicity. Antibody responses targeting the neuraminidase (NA) antigen, or the HA stalk domain have been implicated in protection against influenza. Responses to the NA and HA-stalk domain following pandemic inactivated influenza are not well characterized in humans., Material and Methods: In a series of clinical trials, we determine the vaccines' NA content and demonstrate that NA inhibition (NAI) antibody responses increase in a dose-dependent manner following a 2-dose priming series with AS03-adjuvanted influenza A(H7N9) inactivated vaccine (A(H7N9) IIV). NAI antibody responses also increase with interval extension of the 2-dose priming series or following a 5-year delayed boost with a heterologous adjuvanted A(H7N9) IIV. Neither concomitant seasonal influenza vaccination given simultaneously or sequentially, nor use of heterologous A(H7N9) IIVs in the 2-dose priming series had an appreciable effect on NAI antibody responses. Anti-HA stalk antibody responses were minimal and not durable., Conclusions: We provide evidence for strategies to improve anti-neuraminidase responses which can be further standardized for pandemic preparedness., Clinical Trial Registry Numbers: NCT03312231, NCT03318315, NCT03589807, NCT03738241., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Background: Human infections with the avian influenza A(H7N9) virus were first reported in China in 2013 and continued to occur in annual waves. In the 2016/2017 fifth wave, Yangtze River Delta (YRD) lineage viruses, which differed antigenically from those of earlier waves, predominated., Methods: In this phase 2 double-blinded trial we randomized 720 adults ≥ 19 years of age to receive two injections of a YRD lineage inactivated A/Hong Kong/125/2017 fifth-wave H7N9 vaccine, given 21 days apart, at doses of 3.75, 7.5, and 15 µg of hemagglutinin (HA) with AS03A adjuvant and at doses of 15 and 45 µg of HA without adjuvant., Results: Two doses of adjuvanted vaccine were required to induce HA inhibition (HI) antibody titers ≥ 40 in most participants. After two doses of the 15 µg H7N9 formulation, given with or without AS03 adjuvant, the proportion achieving a HI titer ≥ 40 against the vaccine strain at 21 days after the second vaccination was 65 % (95 % CI, 57 %-73 %) and 0 % (95 % CI, 0 %-4%), respectively. Among those who received two doses of the 15 µg adjuvanted formulation the proportion with HI titer ≥ 40 at 21 days after the second vaccination was 76 % (95 % CI, 66 %-84 %) in those 19-64 years of age and 49 % (95 % CI, 37 %-62 %) in those ≥ 65 years of age. Responses to the adjuvanted vaccine formulations did not vary by HA content. Antibody responses declined over time and responses against drifted H7N9 strains were diminished. Overall, the vaccines were well tolerated but, as expected, adjuvanted vaccines were associated with more frequent solicited systemic and local adverse events., Conclusions: AS03 adjuvant improved the immune responses to an inactivated fifth-wave H7N9 influenza vaccine, particularly in younger adults, but invoked lower responses to drifted H7N9 strains. These findings may inform future influenza pandemic preparedness strategies., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [LAJ reports funding support to her institution from Pfizer for the conduct of a clinical trial of an investigational influenza vaccine. NGR is a paid safety consultant for ICON and EMMES, serves on the advisory boards for GSK, Moderna, Sanofi, and Seqirus and her institution received funds for the conduct of research from Sanofi, Lilly, Merck, Quidel, and Pfizer. MJM reported potential competing interests: laboratory research and clinical trials contract funding with Lilly, Pfizer, and Sanofi; personal fees for Scientific Advisory Board service from Merck, Meissa Vaccines, Inc. and Pfizer. EBW has received funding support from Pfizer, Moderna, Sequiris, Najit Technologies Inc, and Clinetic for the conduct of clinical trials and clinical research and has served as an advisor to Vaxcyte and consultant to ILiAD biotechnologies. CAR.’s institution has received funds to conduct clinical research unrelated to this manuscript from BioFire Inc, GSK, MedImmune, Micron, Janssen, Merck, Moderna, Novavax, PaxVax, Pfizer, Regeneron, Sanofi-Pasteur. She is co-inventor of patented RSV vaccine technology unrelated to this manuscript, which has been licensed to Meissa Vaccines, Inc.]., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Lower respiratory tract infections are frequently treated with antibiotics, despite a viral cause in many cases. It remains unknown whether low procalcitonin concentrations can identify patients with lower respiratory tract infection who are unlikely to benefit from antibiotics. We aimed to compare the efficacy and safety of azithromycin versus placebo to treat lower respiratory tract infections in patients with low procalcitonin., Methods: We conducted a randomised, placebo-controlled, double-blind, non-inferiority trial at five health centres in the USA. Adults aged 18 years or older with clinically suspected non-pneumonia lower respiratory tract infection and symptom duration from 24 h to 28 days were eligible for enrolment. Participants with a procalcitonin concentration of 0·25 ng/mL or less were randomly assigned (1:1), in blocks of four with stratification by site, to receive over-encapsulated oral azithromycin 250 mg or matching placebo (two capsules on day 1 followed by one capsule daily for 4 days). Participants, non-study clinical providers, investigators, and study coordinators were masked to treatment allocation. The primary outcome was efficacy of azithromycin versus placebo in terms of clinical improvement at day 5 in the intention-to-treat population. The non-inferiority margin was -12·5%. Solicited adverse events (abdominal pain, vomiting, diarrhoea, allergic reaction, or yeast infections) were recorded as a secondary outcome. This trial is registered with ClinicalTrials.gov, NCT03341273., Findings: Between Dec 8, 2017, and March 9, 2020, 691 patients were assessed for eligibility and 499 were enrolled and randomly assigned to receive azithromycin (n=249) or placebo (n=250). Clinical improvement at day 5 was observed in 148 (63%, 95% CI 54 to 71) of 238 participants with full data in the placebo group and 155 (69%, 61 to 77) of 227 participants with full data in the azithromycin group in the intention-to-treat analysis (between-group difference -6%, 95% CI -15 to 2). The 95% CI for the difference did not meet the non-inferiority margin. Solicited adverse events and the severity of solicited adverse events were not significantly different between groups at day 5, except for increased abdominal pain associated with azithromycin (47 [23%, 95% CI 18 to 29] of 204 participants) compared with placebo (35 [16%, 12 to 21] of 221; between-group difference -7% [95% CI -15 to 0]; p=0·066)., Interpretation: Placebo was not non-inferior to azithromycin in terms of clinical improvement at day 5 in adults with lower respiratory tract infection and a low procalcitonin concentration. After accounting for both the rates of clinical improvement and solicited adverse events at day 5, it is unclear whether antibiotics are indicated for patients with lower respiratory tract infection and a low procalcitonin concentration., Funding: National Institute of Allergy and Infectious Diseases, bioMérieux., Competing Interests: Declaration of interests ELT and CWW report consulting for Biomeme. ELT, CWW, and MTM have a patent pending for Methods to Diagnose and Treat Acute Respiratory Infections (US20180245154A1). Following completion of the study, ELT became an employee of Danaher Diagnostics. EBW is a principal investigator for Pfizer-funded studies of COVID-19 vaccine, a co-investigator for a vaccine study funded by Moderna, and a member of an advisory board for Vaxcyte. NGR serves as a safety consultant for the Emmes Corporation and ICON-I, and reports research funds from Pfizer, Merck, Sanofi, Quidel, and Lilly. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background and Objectives: Despite a high burden of human papillomavirus (HPV)-attributable cancers, the southern US lags other regions in HPV vaccination coverage. This study sought to characterize and contextualize predictors of HPV vaccination in the southern US., Methods: From December 2019 - January 2020, parents of adolescents (ages 9-17 years) living in thirteen southern US states were recruited from a nationally-representative online survey panel and completed a cross-sectional survey. The primary study outcome was initiation of HPV vaccination., Results: Of 1105 parents who responded to the survey, most were ≥35 years of age and of female gender. HPV vaccination initiation was reported only among 37.3% of adolescents and was highest at age 12. Cumulative HPV vaccination coverage was highest at age 15 (60%) but lower than coverage for tetanus-diphtheria-acellular pertussis (Tdap, 79.3%) and Meningococcal vaccines (MenACWY, 67.3%). Provider recommendation was strongly associated with higher odds of HPV vaccination (aOR: 49.9, 95 %CI: 23.1-107.5). In alternative predictive models, home/online (vs. public) schooling and parents' working status were associated with lower odds of vaccination; health care visits in the past 12 months and shorter travel times to adolescents' usual health care provider were associated with greater odds of vaccination., Conclusions: Our findings suggest missed opportunities for HPV vaccination in the southern US and support strengthening provider recommendation for on-time initiation of HPV vaccination among adolescents. Other strategies to increase HPV vaccinations may include encouraging co-administration with other adolescent vaccines, increasing vaccine access, and promoting vaccinations for home/online-school students., Competing Interests: Declaration of Competing Interest Dr. Walter is an investigator for Pfizer vaccine studies, an unfunded co-investigator for a Moderna vaccine study, and a member of an advisory board for Vaxcyte. All other authors have no conflicts of interests to declare., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Influenza viruses cause substantial annual morbidity and mortality globally. Current vaccines protect against influenza only when well matched to the circulating strains. However, antigenic drift can cause considerable mismatches between vaccine and circulating strains, substantially reducing vaccine effectiveness. Moreover, current seasonal vaccines are ineffective against pandemic influenza, and production of a vaccine matched to a newly emerging virus strain takes months. Therefore, there is an unmet medical need for a broadly protective influenza virus vaccine. We aimed to test the ability of chimeric H1 haemagglutinin-based universal influenza virus vaccine candidates to induce broadly cross-reactive antibodies targeting the stalk domain of group 1 haemagglutinin-expressing influenza viruses., Methods: We did a randomised, observer-blinded, phase 1 study in healthy adults in two centres in the USA. Participants were randomly assigned to one of three prime-boost, chimeric haemagglutinin-based vaccine regimens or one of two placebo groups. The vaccine regimens included a chimeric H8/1, intranasal, live-attenuated vaccine on day 1 followed by a non-adjuvanted, chimeric H5/1, intramuscular, inactivated vaccine on day 85; the same regimen but with the inactivated vaccine being adjuvanted with AS03; and an AS03-adjuvanted, chimeric H8/1, intramuscular, inactivated vaccine followed by an AS03-adjuvanted, chimeric H5/1, intramuscular, inactivated vaccine. In this planned interim analysis, the primary endpoints of reactogenicity and safety were assessed by blinded study group. We also assessed anti-H1 haemagglutinin stalk, anti-H2, anti-H9, and anti-H18 IgG antibody titres and plasmablast and memory B-cell responses in peripheral blood. This trial is registered with ClinicalTrials.gov, number NCT03300050., Findings: Between Oct 10, 2017, and Nov 27, 2017, 65 participants were enrolled and randomly assigned. The adjuvanted inactivated vaccine, but not the live-attenuated vaccine, induced a substantial serum IgG antibody response after the prime immunisation, with a seven times increase in anti-H1 stalk antibody titres on day 29. After boost immunisation, all vaccine regimens induced detectable anti-H1 stalk antibody (2·2-5·6 times induction over baseline), cross-reactive serum IgG antibody, and peripheral blood plasmablast responses. An unsolicited adverse event was reported for 29 (48%) of 61 participants. Solicited local adverse events were reported in 12 (48%) of 25 participants following prime vaccination with intramuscular study product or placebo, in 12 (33%) of 36 after prime immunisation with intranasal study product or placebo, and in 18 (32%) of 56 following booster doses of study product or placebo. Solicited systemic adverse events were reported in 14 (56%) of 25 after prime immunisation with intramuscular study product or placebo, in 22 (61%) of 36 after immunisation with intranasal study product or placebo, and in 21 (38%) of 56 after booster doses of study product or placebo. Disaggregated safety data were not available at the time of this interim analysis., Interpretation: The tested chimeric haemagglutinin-based, universal influenza virus vaccine regimens elicited cross-reactive serum IgG antibodies that targeted the conserved haemagglutinin stalk domain. This is the first proof-of-principle study to show that high anti-stalk titres can be induced by a rationally designed vaccine in humans and opens up avenues for further development of universal influenza virus vaccines. On the basis of the blinded study group, the vaccine regimens were tolerable and no safety concerns were observed., Funding: Bill & Melinda Gates Foundation., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: In response to the emergence of influenza viruses with pandemic potential, we evaluated a swine-origin influenza A/H3N2 variant (H3N2v) vaccine in children., Study Design: This multicenter phase II open-label study assessed the safety and immunogenicity of two doses, 21 days apart, of investigational unadjuvanted subvirion monovalent inactivated H3N2v vaccine administered via intramuscular injection. Children 6-35 months of age received 7.5mcg or 15mcg of hemagglutinin (HA)/dose; children 3-17 years of age received 15mcg HA/dose. Safety and reactogenicity were assessed by measuring the occurrence of solicited injection site and systemic reactions in the 7 days after each vaccination; adverse events were assessed for 42 days and serious adverse events for 7 months after the first vaccination. Immunogenicity was evaluated by measuring hemagglutination inhibition (HAI) and neutralizing (Neut) antibodies to H3N2v prior to and 21 days after each vaccination. Cross-reactivity against seasonal H3N2 strains was evaluated., Results: The H3N2v vaccine was well tolerated. Transient mild to moderate injection site tenderness, pain and erythema was observed, with the most commonly reported systemic reactogenicity being irritability in children 6-35 months, and headache and fatigue in children 9-17 years old. Children 6-35 months old, whether they received 7.5mcg or 15mcg/dose, had low HAI and Neut antibody responses after two doses compared to older children. Children under 9 years of age required two doses of vaccine to demonstrate a response, while 9-17 year olds responded well after one dose. Previous influenza vaccination and older age were associated with higher immune responses to H3N2v vaccine. Children 9-17 years of age also developed cross-reactive antibodies against recent seasonal H3N2 influenza viruses., Conclusion: The H3N2v vaccine was safe and immunogenic in children and adolescents. Age-related increases in immunogenicity against H3N2v and seasonal H3N2 viruses were observed, suggesting prior priming via infection and/or immunization. Clinical trial registry: The trial is registered with clinicaltrial.gov: NCT02100436., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: West Nile virus (WNV) is the most common mosquito-borne infection in the United States. HydroVax-001 WNV is a hydrogen peroxide inactivated, whole virion (WNV-Kunjin strain) vaccine adjuvanted with aluminum hydroxide., Methods: We performed a phase 1, randomized, placebo-controlled, double-blind (within dosing group), dose escalation clinical trial of the HydroVax-001 WNV vaccine administered via intramuscular injection. This trial evaluated 1 mcg and 4 mcg dosages of HydroVax-001 WNV vaccine given intramuscularly on day 1 and day 29 in healthy adults. The two dosing groups of HydroVax-001 were enrolled sequentially and each group consisted of 20 individuals who received HydroVax-001 and 5 who received placebo. Safety was assessed at all study days (days 1, 2, 4 and 15 post dose 1, and days 1, 2, 4, 15, 29, 57, 180 and 365 post dose 2), and reactogenicity was assessed for 14 days after administration of each dose. Immunogenicity was measured by WNV-specific plaque reduction neutralization tests (PRNT 50 ) in the presence or absence of added complement or by WNV-specific enzyme-linked immunosorbent assays (ELISA)., Results: HydroVax-001 was safe and well-tolerated as there were no serious adverse events or concerning safety signals. At the 1 mcg dose, HydroVax-001 was not immunogenic by PRNT 50 but elicited up to 41% seroconversion by WNV-specific ELISA in the per-protocol population (PP) after the second dose. At the 4 mcg dose, HydroVax-001 elicited neutralizing antibody responses in 31% of the PP following the second dose. In the presence of added complement, PRNT 50 seroconversion rates increased to 50%, and 75% seroconversion was observed by WNV-specific ELISA., Conclusions: The HydroVax-001 WNV vaccine was found to be modestly immunogenic and well-tolerated at all dose levels., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Tetanus toxoid, reduced diphtheria toxoid, and acellular pertusiss (Tdap) vaccine is recommended during each pregnancy, regardless of prior receipt. Data on reactogenicity and immunogenicity, particularly after repeated Tdap, are limited. We compared local injection-site and systemic reactions and serologic response following Tdap in (1) pregnant and nonpregnant women and (2) pregnant women by self-reported prior Tdap receipt., Study Design: Pregnant women (gestational age 20-34 weeks) and nonpregnant women receiving Tdap were enrolled in this observational study. Injection-site and systemic reactions were assessed for one week post-vaccination. Pertussis toxin, filamentous hemagglutinin, pertactin, fimbriae, tetanus and diphtheria specific IgG antibody titers were determined by standardized enzyme-linked immunosorbent assay at baseline and 28 days post-vaccination. Reactogenicity and serologic responses were compared by pregnancy status, and within pregnant women by self-reported prior Tdap receipt., Results: 374 pregnant and 225 nonpregnant women were vaccinated. Severe local or systemic reactions or "any" fever were uncommon (≤3% for both groups). Moderate/severe injection-site pain was significantly higher in pregnant (17.9%) versus nonpregnant (11.1%) women, but did not prompt a healthcare visit. Proportions of other moderate/severe or any severe reactions were not significantly higher in pregnant compared to nonpregnant women. Moderate/severe (including pain) and severe reactions were not significantly higher in pregnant women receiving repeat versus first-time Tdap. Antibody titers increased from baseline to post-vaccination for all vaccine antigens in pregnant and nonpregnant women; post-vaccination titers against pertussis toxin and filamentous hemagglutinin were significantly higher in nonpregnant versus pregnant women (p < 0.01)., Conclusion: Tdap was well-tolerated in pregnant and nonpregnant women. Pregnant women were more likely to report moderate/severe pain at the Tdap injection-site compared with nonpregnant women, but did not necessitate medical visits. Prior Tdap receipt did not increase occurrence of moderate/severe local or systemic reactions in pregnant women. Serologic responses to all vaccine antigens were robust. Clinical Trial Registration@ClinicalTrials.gov. NCT02209623. https://clinicaltrials.gov/ct2/show/NCT02209623., (Copyright © 2018. Published by Elsevier Ltd.)

Background: Live attenuated influenza vaccine (LAIV) and inactivated influenza vaccine (IIV) are both licensed for administration to nursing mothers. Little is known about the potential for transmission of LAIV viruses from the mother to the infant and the comparative breast milk antibody responses to LAIV and IIV., Methods: We performed a randomized, double-blind study comparing the immunogenicity of LAIV to IIV when administered to nursing mothers. The safety of LAIV to IIV in women and their infants was also compared. Women received LAIV + intramuscular placebo, or IIV + intranasal placebo on Day 0. Breast milk and nasal swabs (from women and infants) were collected on Days 0, 2, and 8 for detection of LAIV. Breast milk and serum antibody responses were measured at Days 0 and 28. The primary hypothesis was that LAIV would provide superior induction of breast milk IgA responses to influenza as compared to IIV when administered to nursing mothers., Results: Breast milk IgG, breast milk IgA (H1N1 only), serum hemagglutination inhibition (HAI), and serum IgG responses were significantly higher following administration of IIV compared to LAIV. Receipt of either LAIV or IIV was safe in women and their infants. One (1%) LAIV recipient transmitted vaccine virus to her infant who remained well. No influenza virus was detected in breast milk., Conclusions: Breast milk and serum antibody responses were higher for IIV compared to LAIV. LAIV and IIV were safe for nursing women but there was one (1%) possible transmission of LAIV to an infant. This study suggests that IIV may be the preferred vaccine for nursing mothers., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Antipyretics reduce fever following childhood vaccinations; after inactivated influenza vaccine (IIV) they might ameliorate fever and thereby decrease febrile seizure risk, but also possibly blunt the immune response. We assessed the effect of antipyretics on immune responses and fever following IIV in children ages 6 through 47 months., Methods: Over the course of three seasons, one hundred forty-two children, receiving either a single or the first of 2 recommended doses of IIV, were randomized to receive either oral acetaminophen suspension (n = 59) or placebo (n = 59) (double-blinded) or ibuprofen (n = 24) (open-label) immediately following IIV and every 4-8 h thereafter for 24 h. Blood samples were obtained at enrollment and 4 weeks following the last recommended IIV dose. Responses to IIV were assessed by hemagglutination inhibition assay (HAI). Seroprotection was defined as an HAI titer ≥1:40 and seroconversion as a titer ≥1:40 if baseline titer <1:10 or four-fold rise if baseline titer ≥1:10. Participants were monitored for fever and other solicited symptoms on the day of and day following IIV., Results: Significant differences in seroconversion and post-vaccination seroprotection were not observed between children included in the different antipyretic groups and the placebo group for the vaccine antigens included in IIV over the course of the studies. Frequencies of solicited symptoms, including fever, were similar between treatment groups and the placebo group., Conclusions: Significant blunting of the immune response was not observed when antipyretics were administered to young children receiving IIV. Studies with larger sample sizes are needed to definitively establish the effect of antipyretics on IIV immunogenicity., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: The study aims were to determine whether inactivated influenza A/H5N1 vaccine administration elicited cell mediated immune (CMI) responses and the impact of adjuvant, vaccine dose and subject age on these responses., Methods: Adults who were previously primed with either adjuvanted or unadjuvanted, inactivated, A/H5N1/Vietnam/1203/2004 (Clade 1) vaccine or unprimed (received placebo) in previous vaccine studies were randomized to receive one (primed) or two (unprimed) 15- or 90-mcg doses of inactivated, A/H5N1/Indonesia/05/05 (Clade 2) vaccine. Peripheral blood mononuclear cells (PBMCs) were collected and analyzed from a subset of vaccinees to assess CMI responses using IFN-γ and granzyme B ELISPOT assays. Cytokine measurements were performed on PBMC supernatants after stimulation with H5N1 virus., Results: PBMCs were available from 177 participants; 88 and 89 received 15-mcg and 90-mcg of unadjuvanted clade 2 vaccine, respectively. Following H5N1 clade 1 stimulation, IFN-γ but not granzyme B normalized spot-forming cell numbers had statistically significant increased numbers at each of the post-vaccination timepoints compared to baseline in pooled analyses of all vaccine doses and age groups. Clade 2 stimulation resulted in statistically significant increased numbers of IFN-γ cells only 180 days following the last vaccination. Responses were similar among younger and older study participants, as were responses among those primed with alum-adjuvanted or non-adjuvanted clade 1 H5N1 vaccines. The dosage of clade 2 vaccine did not impact CMI responses among primed subjects, but responses were statistically significantly greater in unprimed recipients of the 90-mcg dosage compared to unprimed recipients of the 15-mcg dosage. IFN-γ levels in the supernatants of stimulated PBMC were strongly correlated with IFN-γ ELISPOT results., Conclusion: CMI responses occur in adults administered influenza A/H5N1 inactivated influenza vaccine., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objectives: To estimate hepatitis A vaccine series initiation and completion rates, assess time to vaccination, identify missed opportunities for the hepatitis A vaccine series, and examine factors associated with hepatitis A vaccine series initiation and completion., Methods: We conducted a retrospective, observational study using three healthcare claims databases separately. The study population was comprised of children born between years 2005 and 2009 that were continuously enrolled for at least three and a half years from the date of birth. Every child was followed from date of birth for three and a half years for hepatitis A vaccination., Results: There were 93,735 eligible children from Clinformatics Data Mart, 202,513 from MarketScan Commercial, and 207,545 from MarketScan Medicaid. The overall hepatitis A vaccine series initiation rate was 63.8-79.4% and completion rate was 45.1-66.8% across the three databases. About 62.8-90.1% of the children who never initiated hepatitis A vaccine had at least one well visit from 1 year to three and a half years old. Children were more likely to initiate and complete the hepatitis A vaccine series if they were from more recent birth cohorts, from states with a hepatitis A vaccination recommendation prior to the ACIP universal recommendation, from states with daycare/school entry requirements, were enrolled in an HMO health plan, had pediatricians as primary providers, had more doctor's office/well visits and received MMR/Varicella vaccines., Conclusion: In this study, approximately one in every three to five children remained unvaccinated against hepatitis A. Although the hepatitis A vaccine series initiation and completion improved from 2005 to 2009, vaccine coverage has stabilized in recent years. It is important for providers to identify every opportunity for hepatitis A vaccination and to assure that children get protection from this vaccine-preventable disease., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Quadrivalent human papillomavirus vaccine (HPV4) is recommended as a 3-dose series administered at 0, 1-2, and 6 months. However, this dosing schedule is often not followed leading to longer dosing intervals. We conducted a prospective study to assess antibody titers to HPV4 when dose 2 and/or dose 3 were administered on schedule or delayed. Healthy females (N=331) aged 9-18 years were enrolled at the time of receipt of HPV4 dose 2 or 3. Participants were classified as belonging to one of four groups depending upon timing of receipt of HPV4: both doses on time; only dose 2 delayed later than 90 days; only dose 3 delayed later than 180 days; or both doses 2 and 3 delayed. Pre- and post-dose 3 blood samples were assayed for HPV antibody titers (types 6, 11, 16, and 18). Post-dose 3 geometric mean titers (GMTs) for all HPV types were not significantly lower for any of the delayed dosing groups when compared to the on time group. When compared to the on time group, the post dose 3 GMTs in the delayed dose 3 group were significantly higher (p<0.05) for HPV types 6, 11, and 16. Our findings suggest that delays of dose 2 or 3 do not interfere with immune responses after completion of the 3-dose series. These results support current recommendations to not administer additional doses of HPV4 vaccine if dose 2, dose 3, or both doses have been administered late., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Introduction: Reintroduction of Variola major as an agent of bioterrorism remains a concern. A shortened dosing schedule of Bavarian Nordic's (BN) IMVAMUNE(®) (modified vaccinia Ankara vaccine against smallpox) was compared to the currently recommended 0- and 28-day schedule for non-inferiority by evaluating the magnitude and kinetics of the immune responses., Methods: Subjects were assigned to receive IMVAMUNE or placebo administered subcutaneously on Days 0 and 7, Days 0 and 28, or Day 0. Blood was collected for antibody and cell-mediated immune assays. Subjects were followed for safety for 12 months after last vaccination., Results: The primary endpoint of this study was the geometric mean antibody titers (GMT) at 14 days post last vaccination. Of 208 subjects enrolled, 191 received vaccine (Group: 0+7, Group: 0+28 and Group: 0) and 17 received placebo. Moderate/severe systemic reactogenicity after any vaccination were reported by 31.1%, 25.4%, and 28.6% of the subjects for Group: 0+7, Group: 0+28, and Group: 0, respectively (Chi-square test, P=0.77). Based on BN's Plaque Reduction Assay GMTs, Group: 0+7 was non-inferior to Group: 0+28 at Day 4, 180, and 365 after the second vaccination. On Day 14, Group: 0+7 and Group: 0+28 GMT were 10.8 (CI: 9.0, 12.9) and 30.2 (CI: 22.1, 41.1), respectively. Based on BN's Enzyme-linked immunosorbent assay, the proportion of subjects with positive titers for Group: 0+28 was significantly greater than that for Group: 0+7 after second vaccination at Days 4 and 180. By Day 14 after the second dose, the IFN-γ enzyme-linked immunosorbent spot (ELISPOT) responses were similar for Group: 0+28 and Group: 0+7., Conclusion: Overall, a standard dose of IMVAMUNE (0.5 mL of 1 x 10(8) TCID/mL) administered subcutaneously was safe and well tolerated. A second dose of IMVAMUNE at Day 28 compared to Day 7 provided greater antibody responses and the maximal number of responders. By Day 14 after the second dose, IFN-γ ELISPOT responses were similar for Group: 0+28 and Group: 0+7., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: The influenza A/H1N1 pandemic in 2009 created an urgent need to develop vaccines for mass immunization. To guide decisions regarding the optimal immunization dosage and schedule for adults, we evaluated two monovalent, inactivated, unadjuvanted H1N1 influenza vaccines in independent, but simultaneously conducted, multi-center Phase 2 trials of identical design., Methods: Healthy adults, stratified by age (18-64 years and ≥65 years), were randomized (1:1 allocation), in a double-blind, parallel-group design, to receive two intramuscular doses (21 days apart) of vaccine containing approximately 15 μg or 30 μg of hemagglutinin (HA). Primary endpoints were safety (reactogenicity for 8 days after each vaccination and vaccine-associated serious adverse events during the 7 month study) and immunogenicity (proportion of subjects, stratified by age, achieving a serum hemagglutination inhibition [HI] antibody titer ≥1:40 or a ≥4-fold rise in titer after a single injection of either dosage)., Results: Both vaccines were well-tolerated. A single 15 μg dose induced HI titers ≥1:40 in 90% of younger adults (95% confidence interval [CI] 82-95%) and 81% of elderly (95% CI 71-88%) who received Sanofi-Pasteur vaccine (subsequently found to contain 24 μg HA in the standard potency assay), and in 80% of younger adults (95% CI 71-88%) and 60% of elderly (95% CI 50-70%) who received CSL vaccine. Both vaccines were significantly more immunogenic in younger compared with elderly adults by at least one endpoint measure. Increasing the dose to 30 μg raised the frequency of HI titers ≥1:40 in the elderly by approximately 10%. Higher dosage did not significantly enhance immunogenicity in younger adults and a second dose provided little additional benefit to either age group., Conclusion: These trials provided evidence for policymakers that a single 15 μg dose of 2009 A/H1N1 vaccine would likely protect most U.S. adults and suggest a potential benefit of a 30 μg dose for the elderly., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Rotavirus is the most common cause of severe gastroenteritis in infants and young children worldwide. Health-state utility measures used in economic evaluations of rotavirus vaccines do not reflect differences between mild and severe symptoms of rotavirus gastroenteritis and, therefore, do not adequately capture preferences for non-fatal outcomes associated with rotavirus common in industrialized countries. This paper describes the development and results of a survey specifically designed to develop quality-adjusted time equivalents for rotavirus gastroenteritis among a sample of parents with young children in the United States as an alternative to conventional QALY measures in assessing cost-effectiveness., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The aim of the study was to determine whether reduced doses of trivalent inactivated influenza vaccine (TIV) administered by the intradermal (ID) route generated similar immune responses to standard TIV given intramuscularly (IM) with comparable safety profiles. Recent changes in immunization recommendations have increased the number of people for whom influenza vaccination is recommended. Thus, given this increased need and intermittent vaccine shortages, means to rapidly expand the vaccine supply are needed. Previously healthy subjects 18-64 years of age were randomly assigned to one of four TIV vaccine groups: standard 15 μg HA/strain TIV IM, either 9 μg or 6 μg HA/strain of TIV ID given using a new microinjection system (BD Soluvia™ Microinjection System), or 3 μg HA/strain of TIV ID given by Mantoux technique. All vaccines contained A/New Caledonia (H1N1), A/Wyoming (H3N2) and B/Jiangsu strains of influenza. Sera were obtained 21 days after vaccination and hemagglutination inhibition (HAI) assays were performed and geometric mean titers (GMT) were compared among the groups. Participants were queried immediately following vaccination regarding injection pain and quality of the experience. Local and systemic reactions were collected for 7 days following vaccination and compared. Ten study sites enrolled 1592 subjects stratified by age; 18-49 years [N=814] and 50-64 years [N=778]. Among all subjects, for each of the three vaccine strains, the GMTs at 21 days post-vaccination for both the 9 μg and the 6 μg doses of each strain given ID were non inferior to GMTs generated after standard 15 μg doses/strain IM. However, for the 3 μg ID dose, only the A/Wyoming antigen produced a GMT that was non-inferior to the standard IM dose. Additionally, in the subgroup of subjects 50-64 years of age, the 6μg dose given ID induced GMTs that were inferior to the standard IM TIV for the A/H1N1 and B strains. No ID dose produced a GMT superior to that seen after standard IM TIV. Local erythema and swelling were significantly more common in the ID groups but the reactions were mild to moderate and short-lived. No significant safety issues related to intradermal administration were identified. Participants given TIV ID provided favorable responses to questions about their experiences with ID administration. In conclusion, for the aggregated cohorts of adults 18-64 years of age, reduced doses (6 μg and 9 μg) of TIV delivered ID using a novel microinjection system stimulated comparable HAI antibody responses to standard TIV given IM. The reduced 3 μg dose administered ID by needle and syringe, as well as the 6 μg ID for subjects aged 50-64 years of age generated poorer immune responses as compared to the 15 μg IM dose., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The aims of this study were to determine the percentage of females who after initiating the human papillomavirus (HPV) vaccine series, both completed it and completed it on-time, as well as to examine factors associated with series completion and on-time completion. Using data from the North Carolina Immunization Registry, of 138,823 females analyzed, 55% completed the series, and 28% completed it on-time. Over 83% of those who initiated the vaccine series in 2006 completed it by the final study date, as compared to 32% of those who initiated the vaccine in 2009. On-time dosing rates, however, are declining, and have been hovering at 25% for the last two years of the study. Factors such as African-American race and public funding were significantly associated with lower rates of on-time dosing as well as series completion when compared to White race and private funding, respectively. Among girls and young women who initiate the HPV vaccination series, overall completion rates are low, but if given enough time most of those who begin the series will complete it. Our results suggest that strategies to improve the timely completion of the HPV vaccination series may be needed., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

We assessed the effect of age on immunogenicity to trivalent inactivated influenza vaccine (TIV) by comparing the immune responses to influenza vaccine antigens among three age cohorts of vaccine-naïve children aged 6-11 months, 12-17 months, and 18-23 months. In children 6-23 months of age, antibody responses to TIV appear to increase with increasing age. Despite this finding, TIV was immunogenic even in the youngest age group evaluated, further establishing its value as a tool to protect young children from influenza. The role of age should be considered when assessing improved vaccines to enhance TIV immunogenicity and effectiveness in younger children.