Seroprotection Rates Research Articles

Randomized, double-blind, multi-center, phase III clinical trial to evaluate the immunogenicity and safety of MG1109 (egg-based pre-pandemic influenza A/H5N1 vaccine) in healthy adults

ABSTRACTConsidering the pandemic potential of avian influenza A/H5N1, development of an effective and well-tolerated vaccine is an essential part of pandemic preparedness plans. This phase III, randomized, double-blind study was conducted to assess the immunogenicity and safety profile of an alum-adjuvanted, whole virion, pre-pandemic influenza A/H5N1 vaccine (MG1109). Healthy individuals were randomly assigned, in a 3:1 ratio, to receive two doses of either MG1109 or placebo containing alum gel. Immunogenicity was determined by hemagglutination inhibition (HI) and microneutralization (MN) assays. Solicited and unsolicited adverse events were assessed after vaccination. Among 420 enrolled subjects, 418 were available for safety analysis, and 298 MG1109 recipients were available for per-protocol immunogenicity analyses. According to the HI assays, after two vaccine doses, all three of the Committee for Medicinal Products for Human Use (CHMP) criteria were met against the vaccine strain for all age groups: seroprotection rate = 74.8% (95% CI: 69.9 – 79.8), seroconversion rate = 67.8% (95% CI: 62.5–73.1), and geometric mean titer ratio (GMTR) = 5.9 (95% CI: 5.4 – 6.4). According to the MN assays, the GMTR was 2.4 (95% CI: 2.1 – 2.7) and 7.0 (95% CI: 6.3 – 7.9) three weeks after the first and second vaccine doses, respectively. Solicited local and systemic adverse events were mostly mild to moderate and were not significantly different between MG1109 and placebo recipients. In conclusion, two-dose administration of alum-adjuvanted H5N1 pre-pandemic influenza vaccine (MG1109) was highly immunogenic and tolerable in adults.

Optimal timing of influenza vaccination during 3-week cytotoxic chemotherapy cycles.

Cytopenia occurs frequently during cytotoxic chemotherapy. Little is known about the optimal timing of influenza vaccination for patients receiving chemotherapy. This study compared the immunogenicity of an influenza vaccine administered concurrently with chemotherapy (day 1) and within the cytopenic period (day 11) during 3-week cytotoxic chemotherapy cycles. Adult patients with solid cancer undergoing scheduled 3-week cytotoxic chemotherapy were randomly assigned to receive the 2014-2015 seasonal influenza vaccine on day 1 or 11 during the chemotherapy cycle. Patients were stratified by their age (<60 and ≥60 years) and previous influenza vaccination status. Antibody responses to influenza vaccine strains H1N1, H3N2, and B were measured before and 21 to 28 days after vaccination with a hemagglutination inhibition antibody assay. Ninety-seven patients were randomized into a day 1 group (n = 43) or a day 11 group (n = 54). Eighty-three patients were included in the final analysis. The mean age was 54 (± 11) years. Cancer types included breast (61%) and lung cancer (30%). Baseline characteristics were not significantly different between the groups. Seroprotection rates after vaccination were also not significantly different for the day 1 and 11 groups (strain H1N1, 67% vs 75% [P = .403]; strain H3N2, 77% vs 80% [P = .772]; strain B, 21% vs 27% [P = .472]). Seroconversion rates and postvaccination geometric mean titers were also similar for the groups. Vaccine-related adverse events were more common in the day 11 group (13% vs. 32%; P = .040). The antibody responses to influenza vaccination on days 1 and 11 during a 3-week cytotoxic chemotherapy cycle were comparable. Influenza vaccination can be performed concurrently with cytotoxic chemotherapy or during the cytopenic period. Cancer 2017;123:841-48. © 2016 American Cancer Society.

Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine and an MF59-adjuvanted influenza vaccine after concomitant vaccination in ⩾60-year-old adults

BackgroundConcomitant administration of influenza and pneumococcal vaccines could be an efficient strategy to increase vaccine uptake among older adults. Nevertheless, immune interference and safety issues have been a concern when more than one vaccines are administered at the same time. MethodsSubjects aged ⩾60years were randomized in a 1:1:1 ratio to receive MF59-adjuvanted trivalent inactivated influenza vaccine (MF59-aTIV)+13-valent pneumococcal conjugate vaccine (PCV13) (Group 1), PCV13 alone (Group 2), or MF59-aTIV alone (Group 3). Hemagglutination inhibition (HI) and opsonophagocytic activity (OPA) assays were used to compare immunogenicity after single or concomitant vaccination. ResultsA total of 1149 subjects (Group 1, N=373; Group 2, N=394; Group 3, N=382) were available for the assessment of immunogenicity and safety. All groups met immunogenicity criteria for the influenza vaccine in older adults with similar seroprotection rates, seroconversion rates, and geometric mean titer (GMT) fold-increases, irrespective of concomitant vaccination. For each pneumococcal serotype, OPA titers increased markedly after the PCV13 vaccination, irrespective of the concomitant influenza vaccination. After concomitant administration, the non-inferiority criteria of GMT ratios were met for all three influenza subtypes and 13 pneumococcal serotypes. No vaccine-related serious adverse events occurred. ConclusionsConcomitant MF59-aTIV and PCV13 administration showed no interference with antibody response and showed good safety profiles.(Clinical Trial Number – NCT02215863).

Lower Rates of Influenza Infection Following Two Dose Series of High Dose Vaccination in Plasma Cell Disorders: Results of a Randomized, Double-Blind, Placebo-Assisted Clinical Trial

Background:Plasma cell disorders (PCDs) are commonly associated with immune paresis and these patients are susceptible to common infections, including influenza, which are a major source of morbidity. Although seasonal influenza vaccination is routinely employed in patients with PCDs, the data about its efficacy is limited. One approach to enhancing the efficacy of influenza vaccination is the use of standard dose boosters, and a prior study with multiple myeloma patients suggested modestly improved seroprotection. Another approach may be increasing the amount of antigen in vaccines. Combining the use of higher antigen dose and a booster strategy, we recently reported a pilot study utilizing a two dose series of high-dose influenza vaccine in patients with plasma cell disorders (Branagan, et al, ASH 2015). Specifically, protective hemagglutination antibody inhibition (HAI) titers rose to 49% after one high-dose influenza vaccine and up to 66% following the second dose. These results compared favorably to historical rates of seroprotection achieved in only 5-19% of PCD patients following standard influenza vaccination. Based on these encouraging results, we designed the present randomized study to further evaluate this novel influenza vaccination strategy in PCD patients.Methods:We conducted a double-blind, randomized clinical trial over the 2015-16 flu season, comparing two doses of Fluzone® High-Dose influenza vaccination (separated by 30 days) to the current standard of care influenza vaccination. Patients were allocated to the experimental arm in 2:1 ratio compared to standard of care arm. Standard of care influenza vaccination was considered single age-based vaccination (standard dose <65 years and high-dose ≥ 65 years) and patients in this arm received a saline placebo injection at 30 days to assist in blinding. Eligibility criteria allowed any patient with a plasma cell disorder and no contraindication to trivalent inactivated influenza vaccine. The primary endpoint was laboratory-confirmed flu infection rate. Patients were asked to report all flu-like illnesses for laboratory testing and patients were asked about infectious symptoms at all study visits and at the end of the flu season in May 2016. Secondary endpoints include HAI titer serologic response rates, clinical correlates of protection from influenza infection, and exploratory studies of cell-mediated immunity through characterization of T cell subpopulations, cytokine profiles, and flu-specific T-cell responsiveness.Results:122 total plasma cell disorder patients were enrolled (97 with disease requiring therapy and 25 with asymptomatic gammopathy). Forty-eight patients received a single standard of care influenza vaccination and 74 patients received two doses of Fluzone® High-Dose vaccine. Median age was 67 years (range 42-90). This two-dose vaccination strategy was safely tolerated in all patients with no ³grade 2 adverse events attributed to vaccine. With close clinical follow-up, only 4% of patients receiving two vaccine doses developed laboratory confirmed influenza versus 8.3% of those receiving single vaccine. When compared to the expected CDC influenza infection rate of 10-15%, one sample, two-tailed binomial testing revealed patients receiving two vaccines experienced a significantly lower rate of infection than the expected rate (p<0.05) whereas those receiving single vaccine showed no significant difference (p=0.38). Analysis of HAI titer results, clinical correlates of protection, and measurements of cell-mediated immunity are underway and will be updated for presentation at ASH 2016.Conclusions:This randomized study demonstrates that the two dose strategy of Fluzone® High-Dose influenza vaccine is safely tolerated in patients with plasma cell disorders and associated with significantly less than expected laboratory-confirmed influenza infections. The results suggest that this novel vaccination strategy may have a clinical benefit in reducing influenza infections in PCD patients and thus may have practice changing implications. Final analyses of serologic responses, clinical correlates of response, and cell-mediated immune correlates may provide valuable insights into in vivo "immune-competence" in PCD. DisclosuresNo relevant conflicts of interest to declare.

Immunogenicity and safety of Southern Hemisphere inactivated quadrivalent influenza vaccine: a Phase III, open-label study of adults in Brazil

The World Health Organization influenza forecast now includes an influenza B strain from each of the influenza B lineages (B/Yamagata and B/Victoria) for inclusion in seasonal influenza vaccines. Traditional trivalent influenza vaccines include an influenza B strain from one lineage, but because two influenza B lineages frequently co-circulate, the effectiveness of trivalent vaccines may be reduced in seasons of influenza B vaccine-mismatch. Thus, quadrivalent vaccines may potentially reduce the burden of influenza compared with trivalent vaccines.In this Phase III, open-label study, we assessed the immunogenicity and safety of Southern Hemisphere inactivated quadrivalent influenza vaccine (Fluarix™ Tetra) in Brazilian adults (NCT02369341). The primary objective was to assess hemagglutination-inhibition antibody responses against each vaccine strain 21 days after vaccination in adults (aged ≥18–60 years) and older adults (aged >60 years). Solicited adverse events for four days post-vaccination, and unsolicited adverse events and serious adverse events for 21 days post-vaccination were also assessed.A total of 63 adults and 57 older adults received one dose of inactivated quadrivalent influenza vaccine at the beginning of the 2015 Southern Hemisphere influenza season. After vaccination, in adults and older adults, the hemagglutination-inhibition titers fulfilled the European licensure criteria for immunogenicity. In adults, the seroprotection rates with HI titer ≥1:40 were 100% (A/H1N1), 98.4% (A/H3N2), 100% (B/Yamagata), and 100% (B/Victoria); in older adults were 94.7% (A/H1N1), 96.5% (A/H3N2), 100% (B/Yamagata), and 100% (B/Victoria). Pain was the most common solicited local adverse events in adults (27/62) and in older adults (13/57), and the most common solicited general adverse events in adults was myalgia (9/62), and in older adults were myalgia and arthralgia (both 2/57). Unsolicited adverse events were reported by 11/63 adults and 10/57 older adults.The study showed that inactivated quadrivalent influenza vaccine was immunogenic and well-tolerated in Brazilian adults and older adults.

Immunogenicity of trivalent influenza vaccine in patients with lung cancer undergoing anticancer chemotherapy

ABSTRACTLung cancer is a leading cause of cancer-related death, and patients with lung cancer are a priority group for influenza vaccination. However, few studies have assessed the immunogenicity of the influenza vaccine in these patients. Here, we performed a prospective study to evaluate the immunogenicity of the influenza vaccine in patients with lung cancer undergoing anticancer chemotherapy. Twenty-five patients with lung cancer undergoing anticancer chemotherapy and 26 patients with chronic obstructive pulmonary disease (COPD) as controls were enrolled. A trivalent influenza vaccine containing inactivated A/California/7/2009 (H1N1) pdm09, A/Texas/50/2012 (H3N2), and B/Massachusetts/2/2012 was administered as a single subcutaneous injection. Serum samples were collected before vaccination, and at 4–6 weeks after vaccination. Levels of serum antibody to hemagglutinin were measured. Among patients with lung cancer, the seroprotection rate (postvaccination titer > 1:40) was 84% for both A(H1N1) and A(H3N2), similar to the levels observed in patients with COPD. However, the seroprotection rate for the B strain was significantly lower in patients with lung cancer than in patients with COPD (64% versus 92%). Even after adjustment for potential confounders, patients with lung cancer had a significantly lower odds ratio for seroprotection against the B strain than patients with COPD. Moreover, in patients with lung cancer, those receiving the platinum doublet treatment tended to exhibit a lower seroprotection rate than those receiving a single agent. Thus, patients with lung cancer undergoing anticancer chemotherapy showed acceptable immune responses to a trivalent influenza vaccine, supporting the recommendation for annual influenza vaccination in these patients.

Do Dose Numbers Matter?: Evaluation of Differing Infant and Toddler Meningococcal C Conjugate Vaccine Programs in Canadian Children.

The diversity of Canadian infant meningococcal C conjugate (MenC) vaccine programs is unique among countries providing MenC vaccines and offers a valuable opportunity to determine the optimal vaccine program. This longitudinal study assessed differences in seroprotection by 3 different vaccine schedules in children two years after receiving either 1 toddler MenC vaccine dose (1 dose), 1 infant and 1 toddler dose (2 doses), or 2 infant and 1 toddler MenC vaccine dose (3 doses). Three similar cohorts of healthy infants from 1, 2 and 3 dose program areas were enrolled before to their 12 month toddler dose and vaccinated with MenC-tetanus toxoid (MenC-TT) conjugate vaccine. Sera obtained 2 years later were assayed for serogroup C bactericidal activity using standardized procedures with rabbit as the exogenous complement source. Serum bactericidal activity titers ≥1:8 were considered protective. Results were available for 384 children. Rates of seroprotection at 36 months of age were significantly different between the 1 and 3 dose programs, but confidence intervals overlapped between the 1 and 2 dose programs and between the 2 and 3 dose programs: 1 dose 92% (95% confidence interval: 86%-96%) versus 99% (95%-100%) with 2 doses and 100% (97%-100%) with 3 doses. Geometric mean titers were significantly different at 12.1 (10.8-13.5), 32.4 (28.9-36.2) and 50.6 (45.7-55.9) in the 1, 2 and 3 dose programs, respectively. At 36 months of age, evidence of seroprotection remained for greater than 90% of participants. Our results indicate that 1 toddler dose or 1 infant plus 1 toddler dose with MenC-TT vaccine provides seroprotection against MenC disease in early childhood.

Low and disparate seroprotection after pentavalent childhood vaccination in the Lao People's Democratic Republic: a cross-sectional study

ObjectiveIn Lao People's Democratic Republic, the high burden of vaccine-preventable diseases is thought to be mainly due to low vaccine coverage. We investigated the seroprotective response against diphtheria–tetanus–whole cell pertussis–hepatitis B–Haemophilus influenzae type b (DTPw-HepB-Hib) vaccine in children. MethodsSerum was collected from 1131 children aged 9 to 50 months and their mothers in a cross-sectional study between December 2013 and July 2014. All children had records of three injections of the DTPw-HepB-Hib vaccine. Serum was analysed for hepatitis B surface antigen (HBsAg), anti-HBsAg (anti-HBs), anti–hepatitis B virus core antigen (anti-HBc), anti-diphtheria and anti-tetanus antibodies. Stool samples were collected for detection of parasites. Demographic and nutritional information were also obtained. ResultsProtective levels of anti-HBs antibodies were found in 394 (37.9%) of 1039 children; 529 (55.7%) of 950 and 809 (85.2%) of 950 children were seroprotected against diphtheria and tetanus. Time since vaccination, age, home birth and malnutrition only partially explained the poor vaccine responses. Overall, 81 (7.8%) of 1039 children and 445 (40.3%) of 1105 of mothers were anti-HBc positive. Ten (1.0%) of 1039 of the children and 77 (7.0%) of 1105 of the mothers were HBsAg carriers. ConclusionsAfter a full documented course of vaccination, seroprotective rates were unusually low and disparate against components of the pentavalent vaccine. These can only partially be explained by the negative predictors identified. Although many children had been infected, only few were chronic carriers of HBsAg. Our study demonstrates an urgent need to monitor the serologic response to vaccination, particularly in resource-poor countries.

Lactobacillus gasseri SBT2055 Stimulates Immunoglobulin Production and Innate Immunity after Influenza Vaccination in Healthy Adult Volunteers: a Randomized, Double-blind, Placebo-controlled, Parallel-group Study

Background: Lactobacillus gasseri strain SBT2055 (LG2055) is a human intestine-originating probiotic bacterium and potent probiotic known to exert various health promotion effects, including prevention of abdominal adiposity in rats and humans. A recent finding in mice has suggested that oral administration of LG2055 induces a protective effect against influenza A virus infection. In this context, evidence for efficacy of LG2055 using a human clinical trial was imminently required.Methods: To confirm this in humans, a randomized, double-blind, placebo-controlled, parallel-group study in healthy adult volunteers was conducted to examine the effect of drinkable yogurt (DY) containing LG2055 on influenza vaccine-specific antibody responses as the primary objective and innate immune responses as the secondary objective. Subjects were asked to consume 100 g/day of DY with LG2055 (LG2055 group; n = 94) or without LG2055 (placebo group; n = 94) for 16 weeks. After 4 weeks, all subjects received a trivalent influenza vaccine. Results: We found that the intake of LG2055 DY increased hemagglutination inhibition titers against influenza viruses A/H1N1 and B and the rate of seroprotection against influenza B after vaccination as compared with the intake of placebo DY by healthy volunteers. In support of this result, we confirmed that total IgG and IgA levels in plasma and sIgA production in saliva were also higher in the LG2055 group than in the placebo group. Furthermore, the intake of LG2055 DY enhanced natural killer cell activity and myxovirus resistance A gene expression, which is one of the antiviral genes stimulated by type I or type III Interferons in peripheral blood mononuclear cells.Conclusions: These results strongly indicate that LG2055 activates both the innate and adaptive human immune responses, suggesting the potential to prevent influenza virus infections by providing specific probiotics as complementary foods.Keywords: human clinical trial, innate immunity, influenza virus, Lactobacillus gasseri, vaccine

Long-term follow-up of Japanese encephalitis chimeric virus vaccine: Immune responses in children

BackgroundA single dose of live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) was shown to be immunogenic and well tolerated when given either as a booster to formalin-inactivated Japanese encephalitis (JE)-vaccine (mouse brain-derived vaccine [MBDV])-primed 2–5-year-olds, or as a primary vaccination to JE-vaccine-naïve 12–24-month-old toddlers in Thailand. A 5-year follow-up assessment of immune response persistence over time was conducted. MethodsFour additional visits (at 2, 3, 4, and 5years) for immunologic assessments were added to the original 12-month open-label crossover study, in which 100 healthy children aged 2–5years with a history of two-dose primary vaccination with MBDV (according to the Thai Expanded Program for Immunization schedule), and 200 healthy JE-vaccine-naïve 12–24-month-old toddlers, were randomized 1:1 to receive JE-CV, containing ⩾4 log10 plaque forming units, 1month before or after hepatitis A control vaccine. ResultsIn MBDV-primed 2–5-year-olds (n=78), the immune response to the JE-CV vaccine persisted up to at least 5years after vaccination with a single dose of JE-CV, with all (n=78) children seroprotected at the year 5 visit (geometric mean titers [GMT]: 2521/dil). There was no decrease of seroprotection rate over time (100% at 6months post-vaccination and 96.8% (90.3–98.9) at 5yearspost-vaccination). In JE-vaccine-naïve toddlers, a protective immune response persisted up to at least 5years in 58.8% (50.9–66.4) after a single-dose administration of JE-CV (GMT 26.71/dil; sensitivity analysis). ConclusionsA single-dose of JE-CV as a booster following MBDV administration provided long-lasting immunity. In JE-vaccine-naïve toddlers, despite relatively high seroprotection rates persisting over time, a subsequent booster dose is recommended following a JE-CV primary vaccination for long-term protection.This study was registered on www.clinicaltrials.gov (NCT00621764).

Comparison of seroconversion rates between low-dose intradermal and recommended dose intramuscular hepatitis B vaccination in children

Introduction Massive hepatitis B vaccination is expensive. Re-sults of studies showed that reduced dosage given intradermallyto adults and intramuscularly to children were able to induceseroconversion.Objective To compare the anti-HBs seroconversion (seropositiveand seroprotective) rates between intradermal low-dose of 2 mg(ID-2) and intramuscular recommended dose of 10 mg (IM-10)vaccination against hepatitis B.Methods In a randomized clinical trial, using the hepatitis B plasmavaccine, elementary school children in Tanjung Enim subdistrict,80-168 months of age, were randomly assigned to be given threedoses of either the ID-2 (n=59) or IM-10 (n=64) vaccinations atone month intervals. Seropositive (anti HBs titer &gt;2.1 mIU/l) andseroprotective (anti HBs &gt;10 mIU/l) rates as well as the seroposi-tive and seroprotective geometric mean antibody titers (GMTs) werecompared one month after each inoculation. A p value of &lt;0.1was considered statistically significant.Results One month after the third inoculation, there was no sig-nificant difference in the seropositive rate (95% vs. 89%),seroprotective rate (85% vs. 83%), seropositive GMTs (55.85 mIU/l vs. 61.24mIU/l), and seroprotective GMTs (73.86 mIU/l vs. 72.49mIU/l) between the ID-2 and the IM-10 groups (all with p&gt;0.1)Conclusion Reduced doses of the hepatitis B vaccine given in-tradermally may offer protection against hepatitis B, thus it may beuseful for mass vaccination programs

Rapid immunization effects of a new type of 60 μg hepatitis B vaccine compared with traditional 20 μg hepatitis B vaccines in adults

ABSTRACTBackground: The widely recommended standard schedule of hepatitis B vaccine for adults is months 0, 1 and 6, which takes 6 months to complete. Rapid completion of one vaccination schedule is important to adults because of its low compliance with follow-up doses. A new type of 60 μg Hepatitis B vaccine, made by Shenzhen Kangtai Biological Products Co., LTD., is originally recommended for low or non-responders. The objective of this clinical trial was to test whether this 60 μg hepatitis B vaccine could be used in primary immune population and what is its level of immunogenicity and safety compared with other hepatitis B vaccines.Methods: This is a 2-center randomized controlled study. A total of 1169 healthy adults aged between 25 and 55 who tested negative for HBsAg, anti-HBs, and anti-HBc were eligible for the study and were enrolled from relatively fixed and stable sites, such as villages, schools and large enterprises et al in Xuanhua county in Hebei province and Huaibei county in Anhui province. They were randomized to group A (20 μg Engerix-B® with 0, 1, 6 month intervals), group B (20 μg Kangtai hepatitis B vaccine with 0, 1, 6 month intervals), group C (60 μg Kangtai hepatitis B vaccine with 0, 2 month intervals) and group D (20 μg Huabei hepatitis B vaccine made by recombinant DNA techniques in CHO cell with 0, 1, 6 month intervals). In group A, B and D, every study object's blood sample was collected in the second month after their final injection to test the anti-HBs levels; while in group C, the blood sample was collected in the second month after the first and the second injection to test the anti-HBs levels. Adverse events were collected after each dose to assess the vaccines' safety.Results: The seroprotection rates were 93.17%, 97.23%, 93.54% and 98.98% respectively and the geometric mean titers (GMTs) were 1033.38 mIU/ml, 600.75 mIU/ml, 265.69 mIU/ml and 1627.05 mIU/ml in group A,B,C and D respectively. The difference of seroprotection rate among the 4 groups was statistically significant (χ2 = 17.26, P<0.05). The difference of titers of anti-HBs among the 4 groups was statistically significant (H = 162.42, P<0.05). BMI, age (older than 40) and smoking were the influence factors of anti-HBs levels on 60 μg hepatitis B vaccine.Conclusion: 60 μg hepatitis B vaccine has a satisfactory safety and seroprotection rate in adult, It could be used in rapid adult hepatitis B immunization.

Randomized safety and immunogenicity trial of a seasonal trivalent inactivated split virion influenza vaccine (IVACFLU-S) in healthy young Vietnamese adults

BackgroundUnder the auspices of the World Health Organization (WHO) Global Action Plan, PATH supported evaluation of a trivalent, seasonal inactivated influenza vaccine candidate produced by the Institute of Vaccines and Medical Biologicals (IVAC), a Vietnamese manufacturer. MethodsIn 2015, 60 healthy adult subjects 18–45years of age were enrolled in a Phase 1, single center, double blind, randomized, placebo-controlled study conducted at a district health center in Thai Binh Province, Vietnam. The study evaluated the overall safety and immunogenicity of a seasonal, trivalent inactivated split virion influenza vaccine. Volunteers were given either vaccine or placebo in a randomized 1:1 ratio.After undergoing screening, eligible volunteers provided their signed consent and were enrolled in the study. On the first day of immunization, randomly chosen volunteers received IVACFLU-S 15μg (mcg) hemagglutinin of each of the three strains in 0.5mL or placebo by intramuscular injection. All volunteers were monitored for adverse events and underwent blood testing at screening and Day 8 to assess the vaccine candidate’s safety. Sera obtained before and 21days after immunization were tested for influenza antibody titers using the hemagglutination-inhibition (HAI) and microneutralization tests (MNT). ResultsVaccine was well tolerated, and there were no serious adverse events reported. HAI and MNT identified serum antibody responses against the three influenza strains in nearly all volunteers who received the vaccine. Overall, serum HAI responses of fourfold or greater were observed in 93 percent, 83 percent, and 77 percent of H1, H3, and B strains, respectively. Seroprotection rates were also very high. ConclusionsIVAC’s seasonal, trivalent influenza vaccine was safe and well tolerated and induced high levels of seroconversion and seroprotection rates. These clinical data are a first step towards demonstrating the feasibility of producing the vaccine locally and that seasonal vaccine production in Vietnam may be an effective strategy for enhancing the global influenza vaccine supply. ClinicalTrials.gov number NCT02598089, October 15, 2015.

The priming effect of previous natural pandemic H1N1 infection on the immunogenicity to subsequent 2010-2011 influenza vaccination in children: a prospective cohort study

BackgroundThe effect of previous natural pandemic H1N1 (H1N1 pdm09) influenza infection on the immunogenicity to subsequent inactivated influenza vaccination in children has not been well studied. We aimed to evaluate the effect of H1N1 pdm09 natural infection and vaccination on the immunogenicity to subsequent 2010-2011 seasonal inactivated influenza vaccination in children.MethodsFrom October 2010 to May 2011, we conducted an open-label, multi-center study in children aged 6 months -18 years in Korea. We measured antibody titers with a hemagglutination-inhibition (HI) assay at baseline, 1 month, and 6 months after vaccination with trivalent split or subunit vaccines containing H1N1 pdm, A/H3N2, and B. The subjects were classified into 4 groups depending on the presence of laboratory-confirmed H1N1 pdm09 infection and/or vaccination in the 2009-2010 season; Group I: vaccination (-)/infection(-), Group II: vaccination (-)/infection(+), Group III: vaccination (+)/infection(-), Group IV: vaccination (+)/infection(+).ResultsAmong the subjects in group I, 47 subjects who had a baseline titer >1:10 were considered to have an asymptomatic infection. They were included into the final group II (n = 80). We defined the new group II as the infection-primed (IP) group and group III as the vaccine-primed (VP) group. Seroconversion rate (57.5 % vs 35.9 %, p = 0.001), seroprotection rate at 6 months after vaccination (70.8 % vs 61.8 %, p = 0.032), and GMT at 1 month after vaccination (129.9 vs 66.5, p = 0.002) were significantly higher in the IP group than in the VP group. In the 9–18 year-old group, seroconversion rate and immunogenicity at 1 and 6 months were significantly higher in the IP group than in the VP group. However in the 1–7 year-old age group, there was no significant difference between the two groups.ConclusionsPrevious H1N1 pdm09 infection appears to have positive effects on immunogenicity of subsequent inactivated influenza vaccines against H1N1 pdm09 in older children.

Impact and long-term protection of hepatitis B vaccination: 17 years after universal hepatitis B vaccination in Tunisia.

Hepatitis B virus (HBV) vaccination has been part of the Expanded Programme of Immunization (EPI) in Tunisia since 1995. The aim of this study was to evaluate, for the first time, the impact of mass vaccination in Tunisia 17 years after this programme was implemented, and in parallel, assess the long-term persistence of anti-HBs antibody in the vaccinated Tunisian population. A total of 1422 students were recruited (703 vaccinated, 719 non-vaccinated). HBV seromarkers were checked. None of the students from either group had positive HBsAg. The overall prevalence of anti-HBc was 0·8%. A Significantly higher prevalence of anti-HBc was noted in unvaccinated students than in vaccinated (1·4% vs. 0·3%, P = 0·02). The overall seroprotection rate (anti-HBs titre ⩾10 mIU/ml) was 68·9% in vaccinated subjects. Seroprotection rates and geometric mean titres decreased significantly with increasing age, reflecting waning anti-HBs titre over time. No significant difference was detected between seroprotection rates and gender or students' area of origin. Incomplete vaccination was the only factor associated with an anti-HBs titre <10 mIU/ml. This study demonstrates the excellent efficacy of the HBV vaccination programme in Tunisia 17 years after its launch. However, a significant decline of anti-HBs seroprotection has been observed in ⩾15-year-old adolescents which places them at risk of infection. Additional studies are needed in hyperendemic regions in Tunisia.

Immunogenicity and safety of a fully liquid aluminum phosphate adjuvanted Haemophilus influenzae type b PRP-CRM197-conjugate vaccine in healthy Japanese children: A phase III, randomized, observer-blind, multicenter, parallel-group study

BackgroundBroad use of monovalent Haemophilus influenzae type b (Hib) conjugate vaccines based on the capsular polysaccharide polyribosyl-ribitol phosphate (PRP), has significantly reduced invasive Hib disease burden in children worldwide, particularly in children aged <1year. In Japan, PRP conjugated to tetanus toxoid (PRP-T) vaccine has been widely used since the initiation of public funding programs followed by a routine vaccination designation in 2013. MethodsWe compared the immunogenicity and safety of PRP conjugated to a non-toxic diphtheria toxin mutant (PRP-CRM197) vaccine with the PRP-T vaccine when administered subcutaneously to healthy Japanese children in a phase III study. Additionally, we evaluated the immunogenicity and safety profiles of a diphtheria–tetanus acellular pertussis (DTaP) combination vaccine when concomitantly administered with either PRP-CRM197 or PRP-T vaccines. The primary endpoint was the “long-term seroprotection rate”, defined as the group proportion with anti-PRP antibody titers ⩾1.0μg/mL, after the primary series. ResultsLong-term seroprotection rates were 99.3% in the PRP-CRM197 group and 95.6% in the PRP-T group. The intergroup difference (PRP-CRM197 group – PRP-T group) was 3.7% (95% confidence interval: 0.099–7.336), demonstrating that PRP-CRM197 vaccine was non-inferior to PRP-T vaccine (p<0.0001). Furthermore, the “short-term seroprotection rate” (anti-PRP antibody titer ⩾0.15μg/mL) before booster vaccination was higher in the PRP-CRM197 group than in PRP-T. Concomitant administration of PRP-CRM197 vaccine with DTaP vaccine showed no differences in terms of immunogenicity compared with concomitant vaccination with PRP-T vaccine and DTaP vaccine. Although CRM197 vaccine had higher local reactogenicity, overall, both Hib vaccines had acceptable safety and tolerability profiles. ConclusionThe immunogenicity of PRP-CRM197 vaccine administered subcutaneously as a three-dose primary series in children followed by a booster vaccination 1year after the primary series induced protective levels of Hib antibodies with no safety or tolerability concerns.Clinical trial registry: Registered on ClinicalTrials.gov: NCT01379846

Immunogenicity and safety of the inactivated Japanese encephalitis vaccine IXIARO® in elderly subjects: Open-label, uncontrolled, multi-center, phase 4 study

BackgroundIXIARO® is a Vero cell-derived, inactivated Japanese encephalitis (JE) vaccine licensed mainly in western countries for children and adults traveling to JE endemic areas. Limited immunogenicity and safety data in elderly travelers have been available. ObjectivesTo evaluate safety and immunogenicity of IXIARO in elderly subjects. MethodsOpen-label, single arm, multi-centered study. Two-hundred subjects with good general health, including adequately controlled chronic conditions, received two doses of IXIARO®, 28days apart. Protective levels of antibodies were tested 42days after the second dose. Systemic and local adverse events (AEs) were solicited for 7days after each dose, unsolicited AEs were collected up to day 70 and in a phone call at month 7. Summary of resultsSubjects were aged 64–83years (median 69.0years). Nineteen percent of subjects had serious or medically attended AEs up to Day 70 (primary endpoint), none of them causally linked to IXIARO. Solicited local AEs were reported by 33.5% (most common: local tenderness) and solicited systemic AEs by 27% (most common: headache) of subjects. The seroprotection rate was 65% with a geometric mean titre (GMT) of 37. Subjects with tick borne encephalitis (TBE) vaccinations in the past 5years (N=29) had a SCR of 90% and GMT of 65. ConclusionsIXIARO is generally well tolerated in the elderly, and the safety profile is largely comparable with younger adults. SCR and GMT are lower compared to younger adults, but SCR is in the range reported in elderly for other vaccines e.g. against TBE, hepatitis-A virus (HAV)/hepatitis-B virus (HBV), influenza. The differences in SCR and GMT from younger to elderly adults were in the range of other vaccines.Duration of protection is uncertain in older persons, therefore a booster dose (third dose) should be considered before any further exposure to JE virus.

The immunogenicity and safety of a tetravalent measles-mumps-rubella-varicella vaccine when co-administered with conjugated meningococcal C vaccine to healthy children: A phase IIIb, randomized, multi-center study in Italy

IntroductionMultiple vaccination visits and administrations can be stressful for infants, parents and healthcare providers. Multivalent combination vaccines can deliver the required number of antigens in fewer injections and clinic visits, while vaccine co-administration can also reduce the number of visits. This non-inferiority study was undertaken to evaluate the feasibility of co-administering a combined measles-mumps-rubella-varicella (MMRV) vaccine with conjugated meningococcal C (MenC) vaccine in a large cohort of healthy Italian toddlers. MethodsHealthy subjects aged 13–15months were randomized (2:1:1) to receive single doses of either: co-administered MMRV+MenC at the same visit (MMRV+MenC group); or MMRV followed 42days later by MenC (MMRV group); or MenC followed 42days later by MMRV (MenC group). Blood samples were collected before and 43days after vaccination. Antibody titers against MMRV were measured using ELISA. Functional-anti-meningococcal-serogroup activity (rSBAMenC) was assessed using a serum bactericidal test. Solicited local and general reactions were recorded for up to 4 and 42days post-vaccination, respectively. Non-inferiority of MMRV+MenC to MMRV (post-dose-1 seroconversion rates) and MMRV+MenC to MenC (post-dose-1 seroprotection rates) was achieved if the lower limit (LL) of the 95% confidence interval (CI) for the group difference was ⩾−10% for each antigen. Results716 subjects were enrolled in the study. At 42days post-vaccination, the MMRV seroconversion rates were 99.3% (measles), 94.5% (mumps), 100% (rubella) and 99.7% (varicella) in the MMRV+MenC group, and 99.4%, 93.2%, 100% and 100%, respectively, in the MMRV group. The seroprotection rates against rSBA-MenC were 98.3% in the MMRV+MenC group and 99.3% in the MenC group. Non-inferiority was reached for all the vaccine antigens. The safety profiles were as expected for these vaccines. ConclusionThe immune responses elicited by co-administered MMRV+MenC were non-inferior to those elicited by MMRV or MenC alone and support vaccination of children with both vaccines at a single visit.Clinical Trials registration: NCT01506193.

Factors influencing immunologic response to hepatitis B vaccine in adults.

Hepatitis B was still a worldwide health problem. This study aimed to conducted a systematic review and meta-analysis to assess a more precise estimation of factors that influence the response to hepatitis B vaccine in adults. Our included studies examined seroprotection rates close to the end of vaccination schedules in healthy adult populations. This meta-analysis including 21053 adults in 37 articles showed that a significantly decreased response to hepatitis B vaccine appeared in adults (age ≥ 40) (RR:1.86, 95% CI:1.55–2.23), male adults (RR:1.40, 95% CI:1.22–1.61), BMI ≥ 25 adults (RR:1.56, 95% CI:1.12–2.17), smoker (RR:1.53, 95% CI:1.21–1.93), and adults with concomitant disease (RR:1.39, 95% CI:1.04–1.86). Meanwhile, we further found a decreased response to hepatitis B vaccine appeared in adults (age ≥ 30) (RR:1.77, 95% CI:1.48–2.10), and adults (age ≥ 60) (RR:1.30, 95% CI:1.01–1.68). However, there were no difference in response to hepatitis B vaccine both in alcoholic (RR:0.90, 95% CI:0.64–1.26) and 0-1-12 vs. 0-1-6 vaccination schedule (RR:1.39, 95% CI:0.41–4.67). Pooling of these studies recommended the sooner the better for adult hepatitis B vaccine strategy. More vaccine doses, supplemental/additional strengthening immunity should be emphasized on the susceptible population of increasing aged, male, BMI ≥ 25, smoking and concomitant disease. The conventional 0-1-6 vaccination schedule could be still worth to be recommended.

Hepatitis B Seroprotection and the Response to a Challenging Dose among Vaccinated Children in Red Sea Governorate.

AIM:To assess the long-term effectiveness of hepatitis B virus vaccine and the need for a booster dose among children who received three doses of vaccine during infancy in Red Sea Governorate.METHODS:A cross-sectional study was performed. Interviews with children (9 months to 16 years) and parents were done. Blood samples to assess Hepatitis B markers were tested. Children showing no seroprotection received a booster dose to assess their anamnestic response after four weeks and one year later.RESULTS:None of the participants had evidence of chronic Hepatitis B. The seroprotection rate was 23.3% and it significantly decreased with age. Multivariate logistic analysis revealed that older age was the significant predicting variable for having no seroprotective level, while baseline anti-HBs level < 3.3 IU/L was the predicting variable for not developing early anamnestic response or loss of late anamnestic response.CONCLUSION:Long-term immunity persists among children who received complete series of hepatitis B vaccination during infancy even in absence or reduction of anti-HBs over time. Therefore, a booster dose is not necessary to maintain immunity till the age of sixteen.