Immunogenicity and safety of a Trivalent Influenza HA vaccine in Indonesian infants and children

IntroductionHigh rate of influenza infection in children made influenza vaccination strongly recommended for all person aged >6 months in Indonesia. Bio Farma Trivalent Influenza HA (Flubio®) vaccine has been used in adolescents and adults, resulted in increased seroconversion, seroprotection rates and geometric mean titer (GMT). However, no data is available regarding its efficacy and safety in children. This study aimed to assess the immunogenicity and safety of Flubio® vaccine in infants and children.Materials and methodsThis was a phase II, open-labeled, clinical trial conducted on healthy children aged 6 month-11 years, vaccinated with 1 or 2 doses of Influenza HA vaccine, with a 28-day interval. Flubio® vaccine composed of A/California/7/2009 (H1N1) pandemic 09, A/Texas/50/2012 (H3N2), and B/Massachusetts/2/2012 strain. This study was held at East Jakarta, Indonesia from May until July 2014. A Total of 405 subjects were included and divided into three groups: A(6–35 months), B(3–8 years), and C(9–11 years). Antibody titer was measured at visit V1 (Day 0), V2 (28 days/+7days after the first dose) and V3 (28 days/+7days after second dose). The seroprotection and seroconversion rates were assessed. Safety was assessed up to 28 days following each dose.ResultsA total of 404 subjects completed the study. After vaccination, all subjects achieved seroprotection and increased seroconversion rates, with post-vaccination antibody titer of ≥1:40 HI for all strains. The GMT also increased significantly. Within 30 min after vaccination, 14.6% and 2% had local and systemic reactions; meanwhile, between 30 min to 72 h after vaccination, 35.1% and 13.6% subjects had local and systemic reactions, respectively. Most reactions were mild. No serious adverse event (SAE) was reported related to vaccine.ConclusionFlubio® (Influenza HA Trivalent) vaccine is immunogenic and safe for children aged 6 months-11 years.Trial Registration: The trial is registered at the US National Institutes of Health (ClinicalTrials.gov) #NCT02093260.     

Immunogenicity and safety of a quadrivalent inactivated influenza virus vaccine compared with a comparator quadrivalent inactivated influenza vaccine in a pediatric population: A phase 3, randomized noninferiority study

BackgroundSeqirus 2010 Southern Hemisphere split-virion trivalent inactivated influenza vaccine (IIV3) was associated with increased febrile reactions in children. Studies in vitro concluded that increasing concentrations of splitting agent decreased residual lipids and attenuated proinflammatory cytokine signals associated with fever. We assessed immunogenicity and safety of a quadrivalent inactivated influenza vaccine (IIV4; produced using higher concentration of splitting agent) versus a United States-licensed comparator IIV4 in healthy children aged 5–17 years.MethodsParticipants (N = 2278) were randomized 3:1 and stratified by age (5–8 years; 9–17 years) to receive IIV4 (n = 1709) or comparator IIV4 (n = 569). Primary objective was to demonstrate noninferiority of IIV4 versus comparator IIV4 as assessed by hemagglutination inhibition (HI) geometric mean titer (GMT) ratio (upper bound of two-sided 95% confidence interval [CI] ≤ 1.5) and difference in seroconversion rate (upper bound of two-sided 95% CI ≤ 10%) for all four vaccine strains. HI antibody titers were assessed at baseline and 28 days postvaccination. Solicited and unsolicited adverse events were assessed during each 7- and 28-day postvaccination period, respectively.ResultsIIV4 met immunogenicity criteria for noninferiority. Adjusted GMT ratios (comparator IIV4/IIV4) for A/H1N1, A/H3N2, B/Yamagata, and B/Victoria strains were 1.01 (95% CI; 0.93, 1.09), 1.05 (0.96, 1.15), 0.89 (0.81, 0.98), and 0.92 (0.83, 1.02), respectively. Corresponding values for differences (95% CI) in seroconversion rates (comparator IIV4 minus IIV4) were −3.1 (−8.0, 1.8), 0.4 (−4.5, 5.3), −3.4 (−8.3, 1.5), and −2.0 (−6.9, 2.9). Fever rates were numerically higher, but not statistically different, with IIV4 versus comparator IIV4. No new safety signals were reported.ConclusionIIV4 demonstrated immunological noninferiority to the comparator IIV4 with a clinically acceptable safety profile in children aged 5–17 years. Increased levels of virus splitting agent seem to have reduced fever rates observed in children with Seqirus IIV3, particularly those aged 5–8 years.Funding: Seqirus Pty Ltd; Clinicaltrials.gov identifier: NCT02545543.     

Immunogenicity and safety of a quadrivalent inactivated influenza vaccine in healthy subjects aged 3 to 17 years old: A phase III,open label,single-arm study

BackgroundQuadrivalent influenza vaccines are particularly valuable during seasons in which a mismatch occurs between the predicted influenza B lineage for the trivalent influenza vaccine and the circulating strain. This study evaluated the immunogenicity and safety of a quadrivalent inactivated influenza vaccine AdimFlu-S manufactured in Taiwan for the 2016–2017 influenza season in healthy children.MethodsA total of 174 healthy children aged 3 to 17 years old were separated into 3 groups (Group A: 3–8 years old, vaccine naïve; Group B: 3–8 years old, vaccine non-naïve; Group C: 9–17 years old, any vaccine status). Sera was collected pre and post vaccination for each participant. A hemagglutination inhibition (HAI) assay was utilized to calculate geometric mean titer (GMT), seroprotection rate, and seroconversion rate.ResultsAll enrolled participants completed the study. For the four vaccine strains four weeks after the last vaccination, geometric mean titer ratios (GMTRs) were between 2.9 and 20.9, seroconversion rates were between 42.9% and 90.9%, and seroprotection rates were all above 96.4%. This achieved all immunogenicity endpoints and fulfilled the criteria of the European Medical Agency’s Committee for Medicinal Products for Human Use (CHMP). No serious adverse events (AEs) were reported during the follow-up period of 6 months.ConclusionThis quadrivalent influenza vaccine is demonstrated to be well tolerated and displays robust immunogenicity for each influenza strain. This could potentially improve protection against the antigenically distinct B/Yamagata and B/Victoria lineages.     

Safety,immunogenicity, and lot-to-lot consistency of a quadrivalent inactivated influenza vaccine in children,adolescents, and adults: A randomized,controlled, phase III trial

BackgroundInactivated quadrivalent influenza vaccine (IIV4) containing two influenza A strains and one strain from each B lineage (Yamagata and Victoria) may offer broader protection against seasonal influenza than inactivated trivalent influenza vaccine (IIV3), containing a single B strain. This study examined the safety, immunogenicity, and lot consistency of an IIV4 candidate.MethodsThis phase III, randomized, controlled, multicenter trial in children/adolescents (9 through 17 years) and adults (18 through 60 years) was conducted in Australia and in the Philippines in 2012. The study was double-blind for IIV4 lots and open-label for IIV4 vs IIV3. Children/adolescents were randomized 2:2:2:1 and adults 10:10:10:1 to receive one of three lots of IIV4 or licensed IIV3. Safety data were collected for up to 6 months post-vaccination. Hemagglutination inhibition and seroneutralization antibody titers were assessed pre-vaccination and 21 days post-vaccination.Results1648 adults and 329 children/adolescents received IIV4, and 56 adults and 55 children/adolescents received IIV3. Solicited reactions, unsolicited adverse events, and serious adverse events were similar for IIV3 and IIV4 recipients in both age groups. Injection-site pain, headache, malaise, and myalgia were the most frequently reported solicited reactions, most of which were mild and resolved within 3 days. No vaccine-related serious adverse events or deaths were reported. Post-vaccination antibody responses, seroconversion rates, and seroprotection rates for the 3 strains common to both vaccines were comparable for IIV3 and IIV4 in both age groups. Antibody responses to IIV4 were equivalent among vaccine lots and comparable between age groups for each of the 4 strains. IIV4 met all European Medicines Agency immunogenicity criteria for adults for all 4 strains.ConclusionsIn both age groups, IIV4 was well tolerated and caused no safety concerns, induced robust antibody responses to all 4 influenza strains, and met all EMA immunogenicity criteria for adults.Clinical trial registry numberNCT01481454.     

国产流感裂解疫苗的免疫效果及安全性观察

我国是流感的高发区,每年均有不同程度流行,严重威胁人民健康.接种流感疫苗是预防流感的最佳方法.安全性、免疫原性较好的疫苗将成为未来流感疫苗的发展方向.为了解国产流感病毒裂解疫苗在人群中接种的安全性和免疫效果,并与同类进口流感疫苗做对比,于2006年11月至2007年4月在陕西省屑县进行临床研究,结果报告如下.     

Safety and immunogenicity of a quadrivalent inactivated influenza vaccine in adults

Background and aims

Although two antigenically distinct B strain lineages of influenza have co-circulated globally since the mid-1980s, trivalent influenza vaccines (TIVs) contain only one, resulting in frequent mismatches. This study examined the safety and immunogenicity of an inactivated quadrivalent influenza vaccine (QIV) candidate.

Methods

This was a phase III, randomized, active-controlled, multicenter trial in adults during the 2011/2012 influenza season. Enrollment was stratified to include equal numbers of subjects 18–60 and >60 years of age. Subjects were randomized 5:1:1 to be vaccinated with the QIV, the licensed TIV, or an investigational TIV containing the alternate B strain lineage. Hemagglutinin inhibition antibody titers were assessed pre-vaccination and 21 days post-vaccination.

Results

1116 subjects were vaccinated with QIV, 226 with the licensed TIV, and 223 with the investigational TIV. For all four vaccine strains, antibody responses to the QIV were non-inferior to the response to the TIV for the matched strains. For both B strains, post-vaccination antibody responses to the QIV were superior to the responses to the TIVs lacking the corresponding B strain. The QIV met all European Medicines Agency criteria for all four vaccine strains. Solicited reactions, unsolicited adverse events, and serious adverse events were similar for the QIV and pooled TIV groups. The most commonly reported solicited reactions were injection-site pain, headache, and myalgia, and most solicited reactions were mild or moderate and appeared and resolved within 3 days of vaccination. No treatment-related serious adverse events or deaths were reported.

Conclusions

The inactivated QIV was well tolerated without any safety concerns. For all four vaccine strains, antibody responses to the QIV were superior to the responses to TIV for the unmatched strains and non-inferior for the matched strains. QIV could therefore help address an unmet need due to mismatched B strains in previous influenza vaccines.

Clinical trial registry number

EudraCT: 2011-001976-21.     

Immunogenicity and safety of the third booster dose of the inactivated Japanese encephalitis vaccine in Korean children: A prospective multicenter study

The immunization schedule for the inactivated Japanese encephalitis (JE) vaccine in Korea is a two-dose primary series at 12–24 months of age and three booster doses at 12 months after primary schedule and at 6 and 12 years of age. The aim of this study was to investigate immunogenicity and safety of the third booster dose of the inactivated JE vaccine, as well as the long-term immunogenicity of the second booster dose in Korean children. Healthy children aged 11–13 years, primed and given four doses of inactivated JE vaccines were included. All subjects received the third booster dose of the JE vaccine. Neutralizing antibody (NTAb) titers were assessed before and 4–6 weeks after vaccination using plaque reduction neutralization test (PRNT), and were considered to be protective at ≥ 1:10. Local and systemic adverse events were monitored for 4 weeks after vaccination. Before and after booster vaccination, all seroprotection rates were 100%. Geometric mean titer (GMT) showed a 6.05–fold increase, from 139.11 (95% CI: 110.76, 174.71) to 841.53 (95% CI, 714.25, 991.50). The local tolerability and systemic safety profiles were favorable, with no serious adverse events. In conclusion, the third booster dose of the inactivated JE vaccine was demonstrated to be safe and immunogenic in Korean children when administered according to the current immunization schedule.     

Immunogenicity and safety of inactivated quadrivalent influenza vaccine in adults: A systematic review and meta-analysis of randomised controlled trials

BackgroundA quadrivalent influenza vaccine (QIV) includes two A strains (A/H1N1, A/H3N2) and two B lineages (B/Victoria, B/Yamagata). The presence of both B lineages eliminate potential B lineage mismatch of trivalent influenza vaccine (TIV) with the circulating strain.MethodsElectronic database searches of Medline, Embase, Cochrane Central Register of Controlled Trials (CCRCT), Scopus and Web of Science were conducted for articles published until June 30, 2015 inclusive. Articles were limited to randomised controlled trials (RCTs) in adults using inactivated intramuscular vaccine and published in English language only. Summary estimates of immunogenicity (by seroprotection and seroconversion rates) and adverse events outcomes were compared between QIV and TIV, using a risk ratio (RR). Studies were pooled using inverse variance weights with a random effect model and the I² statistic was used to estimate heterogeneity.ResultsA total of five RCTs were included in the meta-analysis. For immunogenicity outcomes, QIV had similar efficacy for the three common strains; A/H1N1, A/H3N2 and the B lineage included in the TIV. QIV also showed superior efficacy for the B lineage not included in the TIV; pooled seroprotection RR of 1.14 (95%CI: 1.03–1.25, p = 0.008) and seroconversion RR of 1.78 (95%CI: 1.24–2.55, p = 0.002) for B/Victoria, and pooled seroprotection RR of 1.12 (95%CI: 1.02–1.22, p = 0.01) and seroconversion RR of 2.11 (95%CI: 1.51–2.95, p < 0.001) for B/Yamagata, respectively. No significant differences were found between QIV and TIV for aggregated local and systemic adverse events within 7 days post-vaccination. There were no vaccine-related serious adverse events reported for either QIV or TIV. Compared to TIV, injection-site pain was more common for QIV, with a pooled RR of 1.18 (95%CI: 1.03–1.35, p = 0.02).ConclusionIn adults, inactivated QIV was as immunogenic as seasonal TIV, with equivalent efficacy against the shared three strains included in TIV, and a superior immunogenicity against the non-TIV B lineage.     

Immunogenicity and safety of inactivated influenza vaccines in primed populations: a systematic literature review and meta-analysis

Several inactivated influenza vaccine formulations for systemic administration in man are currently available for annual (seasonal) immunization: split virus and subunit (either plain-aqueous, or virosomal, or adjuvanted by MF59). From a literature search covering the period 1978-2009, 33 articles could be identified, which described randomized clinical trials comparing at least two of the four vaccine formulations with respect to serum hemagglutination inhibition (HI) antibody response, local and systemic vaccine reactions and serious adverse events after vaccination, and employing seasonal vaccine components and doses. In total, 9121 vaccinees of all ages, either healthy or with underlying diseases, were involved. Most vaccinees were primed or had been vaccinated in previous years.For immunogenicity, homologous post-vaccination geometric mean HI titers (GMTs) were analyzed by a random effects model for continuous data. Unreported standard deviations (SD) were addressed by imputing assumed SD-values. Age and health state of the vaccinees appeared to have little influence on the outcome. The immunogenicity of split, aqueous and virosomal subunit formulations were similar, with geometric mean ratio values (GMR, quotient of paired GMT-values) varying around one (0.93-1.24). The MF59-adjuvanted subunit vaccine induced, on average, larger antibody titers than the non-adjuvanted vaccine formulations, but the absolute increase was small (GMR-values varying between 1.25 and 1.40).Vaccine reactions were analyzed using a random effects model for binary data. Local and systemic reactogenicity was similar among non-adjuvanted formulations. The adjuvanted subunit formulation was more frequently associated with local reactions than the non-adjuvanted formulations (rate ratio: 2.12, significant). Systemic reactions were similar among all vaccine formulations. The original articles emphasized the mild and transient character of the vaccine reactions and the absence of serious vaccine-related adverse events.This adequate amount of evidence led to the conclusion that all the currently available inactivated influenza vaccine formulations are safe, well tolerated and similarly effective to control seasonal influenza outbreaks across primed populations and age ranges.     

Efficacy,immunogenicity, and safety of a quadrivalent inactivated influenza vaccine in children aged 6–35 months: A multi-season randomised placebo-controlled trial in the Northern and Southern Hemispheres

Background

A quadrivalent split-virion inactivated influenza vaccine (VaxigripTetra?, Sanofi Pasteur; IIV4) containing two A strains (H1N1 and H3N2) and B strains from both lineages (Victoria and Yamagata) was approved in Europe in 2016 for individuals aged?≥?3?years. This study examined the efficacy and safety of IIV4 in children aged 6–35?months.

A novel peptide-based pan-influenza A vaccine: A double blind,randomised clinical trial of immunogenicity and safety

BackgroundFP-01.1 is a novel synthetic influenza A vaccine consisting of six fluorocarbon-modified 35-mer peptides that encapsulate multiple CD4+ and CD8+ T-cell epitopes and is designed to induce an immune response across a broad population.MethodsFP-01.1 was evaluated for safety and immunogenicity in a randomised, double-blind, placebo-controlled, dose-escalation, phase I clinical study in healthy adult volunteers (n = 49). IFNγ ELISpot assays and multicolour flow cytometry were used to characterise the immune response.ResultsFP-01.1 was safe and well tolerated at all doses tested with a similar adverse event profile in actively vaccinated subjects compared with controls. Maximum immunogenicity was in the 150 μg/peptide dose group where a robust response (243 spots/million PBMC) was demonstrated in 75% subjects compared with 0% in placebo controls. All six peptides were immunogenic. FP-01.1 induced dual CD4+ and CD8+ T cell responses and vaccine-specific T cells cross-recognise divergent influenza strains.ConclusionsThis first-in-human study showed that FP-01.1 has an acceptable safety and tolerability profile and generated robust anti-viral T cell responses in a high proportion of subjects tested. The results support the further clinical testing of FP-01.1 prior to clinical, proof-of-concept, live viral challenge studies.     

Immunogenicity and safety of intradermal influenza vaccine in children

In order to compare the immunogenicity and safety of different doses of trivalent influenza vaccine (TIV) administered intradermallly (ID) with those evoked by a full dose of intramuscular (IM) virosomal-adjuvanted influenza vaccine (VA-TIV), 112 previously primed healthy children aged ≥3 years were randomised to receive 9 μg or 15 μg of each strain of ID-TIV, or a full IM dose (15 μg of each strain) of VA-TIV. The A/H1N1 and A/H3N2 seroconversion and seroprotection rates were ≥90% and geometric mean titres (GMTs) increased 3.2-14.9 times without any statistically significant between-group differences; however, the seroconversion and seroprotection rates against the B strain were significantly higher in the children receiving either ID-TIV dose (p < 0.05) without any differences between them. GMT against B virus was significantly higher in the children receiving the highest dose (p < 0.05). Local reactions were significantly more common among the children receiving either ID-TIV dose (p < 0.05), but systemic reactions were relatively uncommon in all three groups. Our findings suggest that ID-TIV with 15 μg of each viral antigen can confer a significant better protection against influenza than that obtained with the same dose of IM TIV in already primed children aged ≥3 years with an acceptable safety profile. The lower dose of ID-TIV needs further evaluation to analyze persistence of protection.     

Immunogenicity and safety of a novel tetanus toxoid-conjugated anti-gastrin vaccine in BALB/c mice

The objective of this study is to determine the immunogenicity and safety of our novel anti-gastrin vaccine that is composed of the common amino-terminal portions of human carboxy-amidated gastrin-17 (G17) and glycine-extended gastrin-17 (gly-G17) as well as the common carboxy-terminal portion of the gastrin precursor progastrin (in a 50:50 mixture) all covalently linked to tetanus toxoid (TT) via peptide spacers.The vaccine, or immunogen, was injected intramuscularly into the legs of BALB/c mice, which produced high serum titres of specific IgG antibodies and IFN-γ in their spleen cells, identifiable by enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunospot assay (ELISPOT), respectively. TT as the protein carrier effectively enhanced the antigenic epitopes’ humoural and cellular immune responses, unlike the antigenic epitopes alone or the immunogen’s adjuvant emulsion system (AES), all of which failed to provoke any obvious immune response. Notably, the animals’ body weights increased significantly after immunization (P < .01), while their haematology and serum biochemistry were all generally normal, and the gross anatomy of their main organs (e.g., heart, liver, spleen, lung, kidney) showed no obvious histopathological changes.     

A Phase III randomised trial of the immunogenicity and safety of quadrivalent versus trivalent inactivated subunit influenza vaccine in adult and elderly subjects,assessing both anti-haemagglutinin and virus neutralisation antibody responses

BackgroundTrivalent influenza vaccines (TIVs) offer substantial protection against matching B-strains, however, protection against alternate-lineage B-strains may be enhanced by adding a second B-strain in quadrivalent influenza vaccines (QIVs). In this Phase III, double-blind, multicentre, randomised study, the immunogenicity and safety of subunit inactivated QIV versus TIV was assessed in adult (aged ≥18 to ≤60 years) and elderly (aged ≥61 years) subjects by analysing a combination of haemagglutinin inhibition (HI) and virus neutralisation (VN).MethodsSubjects (n = 1980) were recruited off season (2015/2016) from 20 centres in five European countries and randomised to receive either QIV (n = 1538), TIV with B-strain of the Victoria lineage (n = 221) or TIV with B-strain of the Yamagata lineage (n = 221). The primary aim was to demonstrate non-inferiority of QIV to TIV for immunogenicity against matched influenza strains based on post-vaccination HI titres. Secondary aims were to show superiority of QIV to TIV for immunogenicity against alternate-lineage B-strains and to characterise the immune response by reverse cumulative distribution (RCD) curves of antibody titres and derived serological parameters for HI and VN. Reactogenicity and occurrence of adverse events were assessed post-vaccination.ResultsQIV elicited a non-inferior immune response for matched strains (upper limit of 95% CI for HI geometric mean ratios [GMRs] <1.5) and a superior response for alternate-lineage B-strains (HI GMRs < 1; p < 0.0001) versus TIV. RCD curves demonstrated that post-vaccination HI and VN titres were higher for QIV versus TIV for both alternate-lineage B-strains. Seroconversion rates and geometric mean fold increases of the VN assay were consistent with the HI assay for all strains in QIV. Reporting rates of local and systemic reactions were similar in both vaccine groups.ConclusionsQIV was non-inferior in immunogenicity to TIV for matched strains and superior to the alternate-lineage B-strains in TIV. Safety and tolerability profiles of QIV and TIV were comparable.     

流行性感冒疫苗的安全性和免疫原性观察

为了解流行性感冒（流感）疫苗，尤其是儿童剂型流感疫苗的安全性和免疫原性，于1999年末在天津市对防感灵的儿童剂型和成人剂型进行了接种后安全性和免疫原性观察，共观察25～55岁成人53名和6月龄～3岁儿童69名。结果表明副反应发生率分别为3.8％和8.7％；抗体阳转率分别为92.2％、85.8％。证实防感灵疫苗儿童剂型和成人剂型均具有良好的免疫原性和安全性。     

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 <1 year. 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 ⩾1.0 μg/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 ⩾0.15 μg/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 1 year after the primary series induced protective levels of Hib antibodies with no safety or tolerability concerns.Clinical trial registry: Registered on ClinicalTrials.gov: NCT01379846     

流行性感冒病毒裂解疫苗安全性与免疫原性研究

目的评价流行性感冒（流感）病毒裂解疫苗的安全性和免疫原性。方法按随机抽样原则,采用单一中心、开放式、接种l剂流感病毒裂解疫苗免疫的方法,开展临床试验。结果观察对象接种1剂后局部反应发生率为0．6％：发热反应发生率4．52％,且以轻度发热为主。血清学检测结果表明,接种疫苗后,流感病毒甲1、甲3、乙（亚）型的血凝抑制（Haemagglutination Inhibition,HAI）抗体总阳转（≥1：40）率分别为95．0％、87．1％、88．1％;HAI抗体几何平均滴度（Geometric Mean Titer,GMT）增长倍数分别为33．28倍、7．76倍、26．04倍;抗体保护率分别为100．0％、99．7％、98．4％。三个型别之间抗体阳转率、GMT增长倍数、保护率的差异有显著的统计学意义。结论国产流感病毒裂解疫苗应用于≥3岁人群是安全的,免疫效果显著。     

国产流感病毒裂解疫苗的免疫原性及安全性效果评价

目的观察国产流感病毒裂解疫苗的免疫原性及安全性。方法通过对疫苗接种者的随访调查和血清学检测,分析国产疫苗和进口疫苗间的免疫差异,从而对国产疫苗进行效果评价。结果接种国产疫苗和进口疫苗后,除个别有发热现象外,未发现其他异常反应,且两组的发热比率经检验差异无统计学意义;国产疫苗H1N1亚型、H3N2亚型和B型HI抗体阳转率、GMT增长倍数以及易感人群下降率,与进口疫苗相比差异均无统计学意义。结论国产疫苗具有很好的安全性和免疫原性。     

Immunogenicity and safety of MenACWY-TT,a meningococcal conjugate vaccine,co-administered with routine childhood vaccine in healthy infants: A phase III,randomized study

BackgroundInvasive meningococcal disease has a high burden in young children, particularly during infancy. We investigated the immunogenicity and safety of a quadrivalent meningococcal conjugated vaccine (MenACWY-TT) co-administered with routine vaccines in healthy infants.MethodsIn this phase IIIb study (NCT01340898) conducted in 2 centers in Lebanon and Mexico, 750 infants were randomized (2:1:1) to receive MenACWY-TT according to 3 schedules: 3+1 (at ages 2, 4, 6 and 15–18 months; group ACWY3+1); 1+1 (at 6 and 15–18 months; group ACWY1+1) or single-dose at 15–18 months (group ACWY1). All infants received PHiD-CV and DTPa-IPV/Hib at ages 2, 4, 6, 15–18 months. Immune responses to MenACWY-TT were assessed by rSBA and hSBA at 7 months (groups ACWY3+1, ACWY1+1) and pre- and post-vaccination at 15–18 months of age (all groups). Immune responses to co-administered vaccines, reactogenicity and safety were also evaluated.ResultsImmunogenicity of MenACWY-TT at 1 month post-primary vaccination was demonstrated in group ACWY3+1: the lower limit of the 95% confidence interval for the percentage of infants with rSBA titers ≥8 was >80% for each serogroup. At 7 months of age, ≥93.9% of MenACWY-TT-primed infants had rSBA titers ≥8. Post-MenACWY-TT vaccination at age 15–18 months, ≥96.3% of participants in all groups had rSBA titers ≥8, regardless of the number of doses received previously. The percentage of infants with hSBA titers ≥4 were ≥87.2% and ≥89.7% at post-primary and booster/single-dose vaccination, respectively. Immune responses to PHiD-CV and DTPa-IPV/Hib did not seem impacted by co-administration with MenACWY-TT in infancy. The incidence of all adverse events was similar among groups. Serious adverse events were reported for 63/750 children in all groups; none were considered vaccine-related by investigators.ConclusionPrimary vaccination with 3 or 1 dose(s) of MenACWY-TT when co-administered with routine pediatric vaccines in infants is immunogenic and well-tolerated.     

Immunogenicity and safety profiles of a new MAV/06 strain varicella vaccine in healthy children: A multinational,multicenter, randomized,double-blinded,active-controlled phase III study

Immunization is the most effective preventive strategy against varicella. While the Oka strain is commonly used for varicella vaccination worldwide, Korea widely uses the MAV/06 strain. A new live attenuated MAV/06 strain varicella vaccine (MG1111), which uses the new cell line Medical Research Council-5 for better viral propagation, was developed. MG1111 was approved by Korean health authorities. Here, we report the results of phase III, randomized, double–blind, multicenter study conducted in Korea and Thailand, which compared the immunogenicity and safety profiles of MG1111 versus the control vaccine, Varivax^TM. In total, 515 healthy children (12 month–12 years) were randomized 1:1 to receive either the MG1111 or control vaccine (MG1111: 258, Control: 257). The seroconversion rate (SCR) and geometric mean titer (GMT) were measured using the fluorescent antibody to membrane antigen (FAMA) test. The MG1111 group achieved a SCR of 97.9% (95% CI: 95.2–99.3) after vaccination. The lower limit of 95% CI for SCR difference (MG1111-Varivax^TM) was –4.0%, which was higher than the specified non-inferiority margin of –10%. Further, the GMT of the MG1111 increased from 2.0 to 74.2 (95% CI: 65.0–84.8) and the lower limits of the 95% CI for post–vaccination GMT ratios (MG1111/Varivax^TM) were 0.55 higher than the specified parameter of 0.5. Therefore, the MG1111 group was not statistically inferior to the control vaccine group in terms of SCR and GMT. Furthermore, the MG1111 and control vaccine groups were not significantly different in the percentage of participants showing adverse events—solicited, local, or systemic during 43-day period of observation and serious adverse events during 6 month of observation. The present results indicate that MG1111was not immunologically inferior to Varivax^TM, and safety profiles of MG1111 are similar to those of Varivax^TM.