CHRONOVAC VOYAGEUR: A study of the immune response to yellow fever vaccine among infants previously immunized against measles

For administration of multiple live attenuated vaccines, the Advisory Committee on Immunization Practices recommends either simultaneous immunization or period of at least 28 days between vaccines, due to a possible reduction in the immune response to either vaccine.The main objective of this study was to compare the immune response to measles (alone or combined with mumps and rubella) and yellow fever vaccines among infants aged 6–24 months living in a yellow fever non-endemic country who had received measles and yellow fever vaccines before travelling to a yellow fever endemic area.Subjects and methods: A retrospective, multicenter case-control study was carried out in 7 travel clinics in the Paris area from February 1st 2011 to march 31, 2015. Cases were defined as infants immunized with the yellow fever vaccine and with the measles vaccine, either alone or in combination with mumps and rubella vaccine, with a period of 1–27 days between each immunization. For each case, two controls were matched based on sex and age: a first control group (control 1) was defined as infants having received the measles vaccine and the yellow fever vaccine simultaneously; a second control group (control 2) was defined as infants who had a period of more than 27 days between receiving the measles vaccine and yellow fever vaccine.The primary endpoint of the study was the percentage of infants with protective immunity against yellow fever, measured by the titer of neutralizing antibodies in a venous blood sample.Results: One hundred and thirty-one infants were included in the study (62 cases, 50 infants in control 1 and 19 infants in control 2). Of these, 127 (96%) were shown to have a protective titer of yellow fever antibodies. All 4 infants without a protective titer of yellow fever antibodies were part of control group 1.Discussion: The measles vaccine, alone or combined with mumps and rubella vaccines, appears to have no influence on humoral immune response to the yellow fever vaccine when administered between 1 and 27 days. The absence of protective antibodies against yellow fever was observed only among infants who received both vaccines simultaneously.Conclusion: These results may support a revision of current vaccination recommendations concerning the administration of these two live attenuated vaccines either on the same day or at least 28 days apart. Our findings show no statistically significant difference if the interval between both vaccines is more than 24 h, but the immune response seems to be reduced when the two vaccines are given at the same time.     

Immunogenicity and safety of the RTS,S/AS01 malaria vaccine co-administered with measles,rubella and yellow fever vaccines in Ghanaian children: A phase IIIb,multi-center,non-inferiority,randomized, open,controlled trial

BackgroundTo optimize vaccine implementation visits for young children, it could be efficient to administer the first RTS,S/AS01 malaria vaccine dose during the Expanded Programme on Immunization (EPI) visit at 6 months of age together with Vitamin A supplementation and the third RTS,S/AS01 dose on the same day as yellow fever (YF), measles and rubella vaccines at 9 months of age. We evaluated the safety and immunogenicity of RTS,S/AS01 when co-administered with YF and combined measles-rubella (MR) vaccines.MethodsIn this phase 3b, open-label, controlled study (NCT02699099), 709 Ghanaian children were randomized (1:1:1) to receive RTS,S/AS01 at 6, 7.5 and 9 months of age, and YF and MR vaccines at 9 or 10.5 months of age (RTS,S coad and RTS,S alone groups, respectively). The third group received YF and MR vaccines at 9 months of age and will receive RTS,S/AS01 at 10.5, 11.5 and 12.5 months of age (Control group). All children received Vitamin A at 6 months of age. Non-inferiority of immune responses to the vaccine antigens was evaluated 1 month following co-administration versus RTS,S/AS01 or EPI vaccines (YF and MR vaccines) alone using pre-defined non-inferiority criteria. Safety was assessed until Study month 4.5.ResultsNon-inferiority of antibody responses to the anti-circumsporozoite and anti-hepatitis B virus surface antigens when RTS,S/AS01 was co-administered with YF and MR vaccines versus RTS,S/AS01 alone was demonstrated. Non-inferiority of antibody responses to the measles, rubella, and YF antigens when RTS,S/AS01 was co-administered with YF and MR vaccines versus YF and MR vaccines alone was demonstrated. The safety profile of all vaccines was clinically acceptable in all groups.ConclusionsRTS,S/AS01 can be co-administered with Vitamin A at 6 months and with YF and MR vaccines at 9 months of age during EPI visits, without immune response impairment to any vaccine antigen or negative safety effect.     

4~6岁儿童接种麻疹-流行性腮腺炎-风疹联合减毒活疫苗加强免疫的免疫原性与安全性研究

目的:探讨4~6岁儿童接种麻疹-流行性腮腺炎-风疹联合减毒活疫苗（MMR）后的加强免疫原性与安全性。方法:分别在山西省、内蒙古自治区以及北京市招募曾有8月龄和18月龄接种过1剂麻疹-风疹联合减毒活疫苗和MMR疫苗免疫史的4~6岁儿童作为研究对象,分为4、5、6岁组,进行MMR疫苗加强免疫研究。接种MMR疫苗前与接种后3...     

Pre-vaccination evolution of antibodies among infants 0, 3 and 6 months of age: A longitudinal analysis of measles,enterovirus 71 and coxsackievirus 16

BackgroundDue to waning levels of maternal antibodies (measles; enterovirus 71, EV71; and coxsackievirus A16, CoxA16), some infants may lose protection against infection prior to vaccination. Using a longitudinal design, we examine how maternal antibody levels evolve over time in infants prior to vaccination.MethodsIn 2013–2014, we collected sera at ages 0, 3 and 6 months from infants. We assayed for levels of measles IgG antibody (717, 233 and 75 sample sera tested at months 0, 3 and 6, respectively), and neutralizing antibodies for EV71 and CoxA16 (225, 217, and 72). Demographic and health information were collected, and a linear mixed model (LMM) was used to describe antibody levels over time.ResultsPre-vaccination monotonic antibody decreases were observed for measles (1410, 195 and 22 mIU/ml, p < 0.001), EV71 (1:19.9, 6.3 and 4.5, p < 0.001) and CoxA16 (1:16.3, 5.9, and 4.5, p < 0.001). At 6 months of age, only 2.7% (95%CI, 0.6–8.3), 6.8% (95%CI, 2.7–14.4) and 5.6% (95%CI, 1.9–12.7) of infants were antibody positive for measles, EV71 and CoxA16, respectively. LMM findings indicated that infants with higher antibody titers at birth experienced a greater loss of antibody level. An infection rate of 1.3% (95%CI, 0.1–6.1) was reported for both EV71 and CoxA16.ConclusionsFurther modifications of vaccination strategies for measles, earlier vaccination for EV71 infection, and deployment of a CoxA16 vaccine need to be considered to limit infection among the very young.     

The strategy for prevention of measles and rubella prevalence with measles–rubella (MR) vaccine in Japan

To eliminate the indigenous measles and rubella virus by 2012 in Japan, the strategy for prevention of measles and rubella prevalence with measles-rubella (MR) vaccine was proposed. Since the vast majority of 1-year old infants are susceptible to measles and rubella, the first MR vaccine should be administered at 1-year old to sustain the herd immunity. Since significant elevation of measles and rubella antibody titers was estimated in a half of children after the second dose, the second dose of MR vaccine within 1 year before elementary school entry is the effective maneuver. Moreover, supplement MR vaccination to the teenage group and 20–29 years’ group might be necessary, because the mean measles antibody titers in this group were significantly lower compared with those in the older individuals’ groups.     

Interchangeability of two Enterovirus 71 inactivated vaccines in Chinese children: A phase IV,open-label,and randomized controlled trial

BackgroundIn China, three inactivated Enterovirus 71 (EV71) vaccines have been approved. Although the vaccines in an immunization series should be from a single manufacture, children sometimes have to receive EV71 vaccines from more than one manufacturers. The aim of this study was to evaluate the interchangeability and safety of vaccination with EV71 vaccines from two manufacturers among Chinese children.MethodsWe conducted an open label and randomized controlled study among children aged 6–35 months from November 2018 to January 2019. The participants were randomly assigned (1:1:1:1) to receive EV71 vaccines in one of the four different schedules (two using a single vaccine for all doses from one manufacture, and two mixed schedules using vaccines from two manufactures). Blood samples were collected pre-vaccination (Day 0) and one month after the second dose (Day 60) for neutralizing antibody assay. Immunogenicity was assessed in the per-protocol cohort and safety was assessed in the total vaccinated cohort.ResultsA total of 300 children were enrolled and randomized, of whom 89.0% (267/300) were included in the per-protocol cohort for immunogenicity analysis. The seroconversion rates of the EV71 neutralizing antibody in four groups ranged from 98.4% to 100.0%, and were not significantly different among the groups. Compared with other groups, geometric mean titer was higher in group D, in which the participants received Institute of Medical Biology Chinese Academy of Medical Sciences (CAMS) vaccine in the first dose and the Sinovac vaccine in the second dose. Safety profiles were similar among the four groups and no serious adverse events related to the vaccination were reported.ConclusionsInterchangeability of EV71 vaccines from two manufactures to complete an immunization series showed good immunogenicity and safety. The antibody response levels may vary by vaccination sequences of EV71 vaccines from the two manufacturers.Trial registration: ClinicalTrials.govNCT03873740.     

Live attenuated vaccine efficacy six months after intravenous immunoglobulin therapy for Kawasaki disease

BackgroundDue to the presence of maternal passive antibodies, the measles vaccine is ineffective if administered before age 12–15 months. The optimal timing for administering a live attenuated vaccine (LAV) after intravenous immunoglobulin therapy (IVIG) for Kawasaki disease (KD) has not been fully investigated. The recommended interval between vaccination and IVIG therapy for KD differs by country. The present study aimed to evaluate efficacy of LAV six months after IVIG therapy for KD in Japan.MethodsThe present, single-arm, prospective, interventional study included patients aged 6 months or older with no medical history of measles, rubella, varicella or mumps or vaccinations against these diseases. The subjects received these vaccinations for the first time at six months after IVIG therapy. Virus-specific IgG levels for each virus measured by EIA was examined at nine months after IVIG therapy. If the results were negative, the subjects received a booster vaccination at 12 months after IVIG therapy. The primary outcome was the prevalence of positivity for antibodies after the initial and booster vaccinations.ResultsThe present study enrolled 32 subjects, 31% of whom were female, with an average age of 10.8 (standard deviation 2.8) months at IVIG therapy. At six months after IVIG therapy, 9% and 6% of the subjects were seropositive for measles and varicella titers, respectively, but were seronegative for the mumps and rubella titers. The seroconversion rate for measles, mumps, rubella, and varicella after the initial vaccination was 88%, 6%, 78%, and 16%, respectively. The seroconversion rate after a booster vaccination was 100% for measles and rubella, 97% for mumps, and 77% for varicella.ConclusionsThe seroconversion rate was low for LAV at six months after a single dose of IVIG for KD, but seroconversion was achievable with a booster vaccination at 12 months.Clinical Trial Registration: UMIN-CTR, UMIN000007174, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000008452.     

2011年北京市大兴区麻风疫苗基础免疫成功率监测结果

目的了解北京市大兴区2011年8月龄儿童接种麻疹风疹联合减毒活疫苗(简称麻风疫苗)后的免疫效果,为制定麻疹免疫策略提供依据。方法采集40名8月龄儿童麻风疫苗免疫前、免疫后1个月双份血标本,分别进行麻疹、风疹IgG抗体测定。结果免后麻疹抗体阳性40人,阳性率100%,GMT 1∶1 385.52;风疹抗体阳性33人,阳性率82.50%,GMT 1∶31.18。结论该区现行的麻风疫苗所包含的麻疹成分免疫原性好,风疹成分免疫效果较差,应进行风疹疫苗复种弥补。     

A randomized trial demonstrating successful boosting responses following simultaneous aerosols of measles and rubella (MR) vaccines in school age children

The reactogenicity and immunogenicity of combined measles and rubella (MR) booster vaccination, via aerosol and subcutaneous routes, was assessed in 562 healthy children. Rates of rubella seroconversion and geometric mean titers (GMT) were similar for both routes. Rates of measles PN seroconversion, GMT and measles ELISA post-vaccination seropositivity and seroconversion rate were each higher for aerosol vaccine (54%, 3928 IU/l, 99.6 and 98.8%), than for subcutaneous vaccine (7%, 866 IU/l, 92.2 and 82.4%) (P<0.01). Reactogenicity was higher for subcutaneous vaccine (P<0.05). This study demonstrates that aerosol vaccine was more immunogenic for measles antibodies, and equally immunogenic for rubella antibodies. Aerosol vaccine was less reactogenic.     

An inactivated enterovirus 71 vaccine is safe and immunogenic in healthy adults: A phase I,double blind,randomized, placebo-controlled,study of two dosages

BackgroundHand, foot and mouth disease (HFMD), especially that caused by enterovirus 71 (EV71) infection, is a public health concern in the Asia-Pacific region. We report a phase I clinical trial of an EV71 candidate vaccine (INV21) based on a binary ethylenimine inactivated B2 sub-genotype formulated with aluminum hydroxide.MethodsIn this double-blind, placebo-controlled, randomized, dose escalation study adult volunteers received two vaccinations 28 days apart of low or high dose formulations of the candidate vaccine and were then monitored for safety and reactogenicity for four weeks after each dose, and for their immune responses up to 28 weeks.ResultsOf 36 adults enrolled, 35 completed the study as planned. Either no or mild adverse events were observed, mainly injection site pain and tiredness. Seroconversion was 100% after two vaccinations. High geometric mean neutralizing antibody titers (GMT) were observed 14 days post first dose, peaking 14 days post second dose (at Day 42) in both high and low dose groups; GMTs on days 14, 28, 42, and 56 were 128, 81, 323, 203 and 144, 100, 451, 351 in low- and high-dose groups, respectively. Titers for both doses declined gradually to Day 196 but remained higher than baseline and the placebo groups, which had low GMTs throughout the duration of the study. Cross-neutralizing antibody activity against heterologous sub-genotypes was demonstrated.ConclusionThese data show that the EV71 candidate vaccine is safe and immunogenic in adults and supports further clinical development as a potential pediatric vaccine by initiating a dose-escalation study for determining the dose-dependent safety and immunogenicity of the vaccine in young naïve children.     

2012年扬州市麻风疫苗效价与基础免疫成功率监测分析

目的了解扬州市麻疹风疹联合减毒活疫苗(简称麻风疫苗)的效价和免疫成功率,考核疫苗管理和冷链运转状况。方法采集60名8月龄儿童麻风疫苗免疫前、后1个月双份血清标本,分别进行麻疹、风疹IgG抗体测定。选择市、县疾病预防控制中心和乡接种点各2支麻风疫苗,采用微量细胞板培养法检测,进行麻风疫苗效价测定。结果免后麻疹抗体阳性59人,阳性率98.33%,免疫成功58人,免疫成功率96.67%,GMT 1∶1 285.13;风疹抗体阳性35人,阳性率58.33%,免疫成功35人,免疫成功率58.33%,GMT 1∶19.67;市、县、乡三个点的麻风疫苗效价均在102.5 TCID50/0.1mL以上,均为合格疫苗。结论扬州市疫苗管理和冷链系统运转状况良好,能保证疫苗的质量。麻风疫苗所包含的麻疹成分免疫原性好,风疹成分免疫原性较差。须进行后续的加强免疫是必要的,还应适时开展大中学生麻风类疫苗追加免疫。     

A double-blind,randomized, controlled,multi-center safety and immunogenicity study of a refrigerator-stable formulation of VARIVAX®

ObjectiveVARIVAX® (varicella virus vaccine, live Oka/Merck, Merck & Co., Inc., Kenilworth, NJ, USA) was originally licensed as a frozen formulation. A refrigerator-stable formulation of VARIVAX was subsequently developed to allow for increased availability of the product around the world. The objective of this study (V210-051) was to demonstrate that the safety, tolerability and immunogenicity profile of the refrigerator-stable formulation of VARIVAX was similar to the frozen formulation.MethodsIn this double-blind, randomized, multicenter study, healthy 12- to 23-month-old children with negative vaccination and clinical histories for measles, mumps, rubella, varicella, and zoster were vaccinated with either a refrigerator-stable formulation of VARIVAX (at two dosage levels; 8000 PFU [N = 320] or 25,000 PFU [N = 315]) or the frozen formulation of VARIVAX (10,000 PFU, N = 323) given concomitantly with M-M-RII® (measles, mumps, and rubella virus vaccine live, Merck & Co., Inc., Kenilworth, NJ, USA). Children were followed for 42 days after vaccination for adverse experiences. Immunogenicity was evaluated 6 weeks after vaccination.ResultsThe refrigerator-stable formulation of VARIVAX was generally well tolerated. The incidence of adverse experiences was similar between all three groups. No vaccine-related serious adverse experiences were reported with any of the vaccine formulations. The immune response (percentage of subjects with varicella antibody titers ≥5 gpELISA units) for both refrigerator-stable formulations of VARIVAX at 6 weeks postvaccination was similar to that of the frozen formulation. Administration of either refrigerator-stable formulation of VARIVAX with M-M-RII yielded seroconversion rates and GMTs for measles, mumps and rubella that were comparable to those achieved after administration of the frozen formulation of VARIVAX with M-M-RII.ConclusionThe safety, tolerability, and immunogenicity profile of the refrigerator-stable varicella vaccine was similar to that of the frozen formulation.     

Safety and efficacy of early vaccination with live attenuated measles vaccine for hematopoietic stem cell transplant recipients and solid organ transplant recipients

Background and objectiveVaccination with the live attenuated measles vaccine is currently recommended two years after hematopoietic stem cell transplantation (HSCT) and generally contraindicated after solid organ transplantation (SOT) due to safety concerns.However, in the last few years new data on the administration of the measles vaccine to HSCT recipients less two years post-transplantation and to SOT recipients have become available.This new data may change current guidelines and practices. The objective of this review is to provide an overview of the current data on the safety and efficacy of early measles vaccination for HSCT- and SOT recipients.MethodPubMed and EMBASE were searched from the earliest date available through October 2019 to identify all research that reported on the safety and efficacy of measles vaccination after SOT or less than two years after HSCT.ResultsA total of ten studies was included in this review. In the six studies that evaluated the efficacy of measles vaccination after SOT, seroconversion rates ranged from 41 to 100% after one dose and 73 to 100% after two doses. In the four studies that evaluated the efficacy of measles vaccination less than two years after HSCT, seroconversion rates ranged from 33 to 100% after one dose and 100% after two doses. In all studies, the administration of the measles vaccine after transplantation was considered to be safe. There were no cases of infection with the attenuated vaccine strain, and there were no adverse events related to the vaccination.ConclusionData on the administration of the measles vaccine after SOT and less than two years after HSCT is scarce. However, the current data available suggest that it is efficacious and well tolerable. Therefore, early measles vaccination could be considered in selected groups of SOT- and HSCT recipients during increased measles transmission or an outbreak setting.     

Mutual interference on the immune response to yellow fever vaccine and a combined vaccine against measles, mumps and rubella

A randomized trial was conducted to assess the immunogenicity and reactogenicity of yellow fever vaccines (YFV) given either simultaneously in separate injections, or 30 days or more after a combined measles-mumps-rubella (MMR) vaccine. Volunteers were also randomized to YFV produced from 17DD and WHO-17D-213 substrains. The study group comprised 1769 healthy 12-month-old children brought to health care centers in Brasilia for routine vaccination. The reactogenicity was of the type and frequency expected for the vaccines and no severe adverse event was associated to either vaccine. Seroconversion and seropositivity 30 days or more after vaccination against yellow fever was similar across groups defined by YFV substrain. Subjects injected YFV and MMR simultaneously had lower seroconversion rates - 90% for rubella, 70% for yellow fever and 61% for mumps - compared with those vaccinated 30 days apart - 97% for rubella, 87% for yellow fever and 71% for mumps. Seroconversion rates for measles were higher than 98% in both comparison groups. Geometric mean titers for rubella and for yellow fever were approximately three times higher among those who got the vaccines 30 days apart. For measles and mumps antibodies GMTs were similar across groups. MMR's interference in immune response of YFV and YFV's interference in immune response of rubella and mumps components of MMR had never been reported before but are consistent with previous observations from other live vaccines. These results may affect the recommendations regarding primary vaccination with yellow fever vaccine and MMR.     

Vitamin A administered with measles vaccine to nine-month-old infants does not reduce vaccine immunogenicity.

After a report of reduced seroconversion to measles in infants, aged 6 mo, given vitamin A with their measles vaccination, serious concerns were raised regarding the safety of the WHO's recommendation that infants be supplemented with vitamin A at the time of measles immunization. To determine the impact of coadministered vitamin A on the antibody response to measles vaccine given to infants aged 9 mo, the more common age for immunization in developing countries, we conducted a randomized, double-blind, placebo-controlled trial in an urban slum community in Delhi. Infants (618) were randomly allocated to receive 30 mg vitamin A or a placebo with the measles immunization. Antibodies to measles were measured by ELISA in serum samples obtained at before (baseline) and 12 wk after immunization. Overall, the seroconversion rates did not differ between vitamin A (89.5%) and placebo (87.6%) groups. There were no significant differences in the geometric mean titers in the two groups (ratio of geometric means, 1.19; 95% confidence interval, 0.97-1.46). Among malnourished infants, the geometric mean titer was significantly greater in the vitamin A group compared to the placebo group (ratio of geometric means, 1.57; 95% confidence interval, 1. 18-2.0), but seroconversion rates did not differ. There were no differences in seroconversion rates and geometric mean titers in the two study groups among the well-nourished children. These results indicate that 30 mg vitamin A does not reduce the immune response to the coadministered vaccine and, therefore, can be continued to be given safely in public health programs.     

婴儿麻疹 风疹减毒活疫苗联合免疫效果观察

为探讨麻疹、风疹减毒活疫苗联合免疫的可行性,于1997年4～12月随机选择了本市342名8月龄婴儿进行了观察．所有入选婴儿被随机分成3组：第1组105人,皮下接种BRD－Ⅱ株风疹疫苗;第2组105人,分别在左、右上臂同时皮下接种BRD—Ⅱ株风疹疫苗和沪191株冻干麻疹疫苗;第3组132人,皮下接种沪191株冻干麻疹疫苗．在免疫前,第1组与第2组的风疹血凝抑制（HI）抗体阳性率均为2．86％,几何平均滴度（GMT）均为1：1．06;第2组与第3组的麻疹HI抗体阳性率分别为2．86％和5.30％,GMT分别为1：1.02和1：1.60.免疫后1个月,第1组与第2组的风疹HI抗体阳性率分别为98.10％和99．05％,GMT分别为1：144.15和1：148.99,两者的差异无显著的统计学意义;第2组与第3组的麻疹HI抗体阳性率分别为99.05％和97.73％,GMT分别为1：35．10和1：32．85,两者的差异亦无显著的统计学意义．所有免疫的儿童均未发现局部和全身反应．结果表明：麻疹、风疹减毒活疫苗联合免疫可产生与常规免疫相同的免疫应答,风疹疫苗初免月龄定于8月龄与麻疹疫苗联合免疫是可行的．     

Immunogenicity and safety of measles-mumps-rubella vaccine delivered by disposable-syringe jet injector in India: A randomized,parallel group,non-inferiority trial

BackgroundWe conducted a randomized, non-inferiority, clinical study of MMR vaccine by a disposable-syringe jet injector (DSJI) in toddlers in India in comparison with the conventional administration.MethodsMMR vaccine was administered subcutaneously by DSJI or needle-syringe (N-S) to toddlers (15–18 months) who had received a measles vaccine at 9 months. Seropositivity to measles, mumps, and rubella serum IgG antibodies was assessed 35 days after vaccination. Non-inferiority was concluded if the upper limit of the 95% CI for the difference in the percent of seropositive between groups was less than 10%. Solicited reactions were collected for 14 days after vaccination by using structured diaries.ResultsIn each study group, 170 subjects received MMR vaccine. On day 35, seropositivity for measles was 97.5% [95% CI (93.8%, 99.3%)] in the DSJI group and 98.7% [95% CI (95.5%, 99.8%)] in the N-S group; for mumps, 98.8% [95% CI (95.6%, 99.8%)] and 98.7% [95% CI (95.5%, 99.8%)]; and for rubella, 98.8% [95% CI (95.6%, 99.8%)] and 100% [95% CI (97.7%, 100.0%)]; none of the differences were significant. The day 35 post-vaccination GMTs in DSJI and N-S groups were measles: 5.48 IU/ml [95% CI (3.71, 8.11)] and 5.94 IU/ml [95% CI (3.92, 9.01)], mumps: 3.83 ISR [95% CI (3.53, 4.14)] and 3.66 ISR [95% CI (3.39, 3.95)] and rubella: 95.27 IU/ml [95% CI (70.39, 128.95)] and 107.06 IU/ml [95% CI (79.02, 145.06)]; none of the differences were significant.The DSJI group reported 173 solicited local reactions and the N-S group reported 112; most were mild grade. Of the total of 156 solicited systemic adverse events, most were mild, and incidence between the two groups was similar.ConclusionsMMR vaccination via DSJI is as immunogenic as vaccination by N-S. Safety profile of DSJI method is similar to N-S except for injection site reactions which are more with DSJI and are well-tolerated.RegistrationUS National Institutes of Health clinical trials identifier – NCT02253407.Clinical trial registry of India identifier – CTRI/2013/05/003702     

Safety and immunogenicity of live-attenuated Japanese encephalitis SA 14-14-2 vaccine co-administered with measles vaccine in 9-month-old infants in Sri Lanka

Introduction

To facilitate introduction of live attenuated SA 14-14-2 Japanese encephalitis vaccine (LJEV) into the National Immunization Programme of Sri Lanka, we evaluated the safety and immunogenicity of co-administration of LJEV and measles vaccine at 9 months of age. Serum immune responses were evaluated post-vaccination on days 28, 180, and 365 using JE neutralization test and anti-measles IgG ELISA.

Results

278 infants received one dose of LJEV and measles vaccine. Of these, 257 were eligible for the per-protocol analysis. On Day 0, 14 infants (5.5%) were seropositive for JE, but none were seropositive for measles. At Day 28, seropositivity rates were 90.7% (95% CI, 86.4–93.9%) for JE and 84.8% (95% CI, 79.8–89.0%) for measles. The geometric mean titer for JE neutralizing antibodies was 111 (95% CI, 90–135), and the geometric mean concentration (GMC) for anti-measles IgG was 375 mIU/mL (95% CI, 351–400 mIU/mL). Over the next year, JE neutralizing antibody responses declined only slightly, with seropositivity at 87.4% (95% CI, 82.6–91.2%) at Day 365. In contrast, measles antibody levels continued to increase over time. Seropositivity for anti-measles IgG reached 97.2% (95% CI, 94.4–98.9%) at Day 365, and the GMC rose to 1202 mIU/mL (95% CI, 1077–1341 mIU/mL). Co-administration of LJEV and measles vaccine was also safe. Most adverse reactions were mild, and no serious adverse events were related to study vaccinations.

Conclusion

The safety and immunogenicity of LJEV co-administered with measles vaccine in Sri Lankan infants is similar to that seen in other populations, and our results support use of LJEV at 9 months of age. Live SA 14-14-2 vaccine is now prequalified by the WHO for use in infants in Asia, and other countries may wish to introduce LJEV to combat this devastating disease.     

Immunogenicity and safety of a combined measles,mumps, rubella and varicella live vaccine (ProQuad®) administered concomitantly with a booster dose of a hexavalent vaccine in 12–23-month-old infants

BackgroundConcomitant administration of vaccines can facilitate vaccination uptake, provided that no clinically significant effect on either vaccine is identified. We investigated the concomitant administration, during the second year of life, of one dose of the combined measles, mumps, rubella and varicella vaccine (ProQuad^®) with a booster dose of a hexavalent vaccine.MethodsIn this multicentre, open-label study, participants were randomized to 3 groups: Group 1, concomitant administration of one dose of ProQuad^® and a booster of hexavalent vaccine; Group 2, one dose of ProQuad^® alone; Group 3, a booster dose of hexavalent vaccine alone. Two serum samples were collected, within 7 days prior to vaccination and Days 42–56 post-vaccination for antibody testing.ResultsAntibody response rates to measles, mumps, rubella, varicella, hepatitis B and Haemophilus influenzae type b following concomitant administration of ProQuad^® and hexavalent vaccine were non-inferior compared with those following the individual vaccines. Antibody response rates to these antigens were all >95% in all groups. Antibody titres for the pertussis antigens following concomitant administration were also non-inferior to those following the individual vaccines. Antibody titres for the other valences were numerically comparable between groups with the exception of hepatitis B, Haemophilus influenzae type b, tetanus and poliomyelitis, which were higher in the concomitant than in the non-concomitant groups. The safety profiles of each vaccination regimen were comparable, with the exception of solicited ProQuad^®-related injection-site reactions (Days 0–4), which occurred more frequently in the concomitant than in the non-concomitant groups.ConclusionThese immunogenicity data support the concomitant administration of ProQuad^® with a hexavalent vaccine. The safety profile of concomitant ProQuad^® and hexavalent vaccination was also in line with that of the individual Summaries of Product Characteristics.     

Clinical evaluation of a new measles-mumps-rubella combined live virus vaccine in the Dominican Republic

Over 900 children were enrolled in a double-blind placebo-controlled clinical study of measles (Schwarz strain), mumps (Jeryl Lynn strain), and rubella (Cendehill strain) trivalent vaccine. The trivalent vaccine caused about the same degree of reactivity as is generally associated with the Schwarz strain measles vaccine. Paired sera from triplesusceptible vaccinees had seroconversion rates of 99% for measles, 94% for mumps, and 93% for rubella. The results of this study show that this trivalent vaccine is as well tolerated and as effective as its component vaccines.