Seroprotection Rates Research Articles

Evaluation of Waning Immunity at 6 Months after Both Trivalent and Quadrivalent Influenza Vaccination in Korean Children Aged 6-35 Months.

BackgroundThe titer of influenza vaccine-induced antibodies declines over time, and younger children have lower immunogenicity and shorter duration of immunity. This study aimed to compare persistence of antibody at 6 months after influenza vaccination according to influenza virus strains, vaccine type, antigen dose, and primed status in children aged 6 to 35 months.MethodsA total 124 healthy children aged 6 to 35 months were enrolled from September to December 2016 at 10 hospitals in Korea and randomly assigned to either a full dose of quadrivalent influenza vaccine or a half dose of trivalent influenza vaccine with Victoria B strain group. Hemagglutination inhibition antibody titers (that measure the seroprotection rates) were assessed for the recommended influenza strains at 6 months post vaccination.ResultsThe seroprotection rates at 6 months for strains A (H1N1), A (H3N2), B/Yamagata, and B/Victoria were 88.7%, 97.4%, 36.6%, and 27.6%, respectively. The seroprotection rates for A (H1N1), A (H3N2) and B (Victoria) were 91.4%, 98.7% and 27.5% in a full dose of quadrivalent vaccine vs. 83.7%, 94.6% and 27.9% in a half dose trivalent vaccine, respectively. The seroprotection rate for the B (Yamagata) strain was 23.8% in the quadrivalent group and 14.0% in the trivalent group.ConclusionPersistence of antibodies at 6 months was more favorable against the influenza A strains than against the B strains. Persistence of antibodies to additional B strain at 6 months was superior in the quadrivalent vaccine group. The immunity of primed children with different B strains was not superior to that of the unprimed group with another B strain.

Comparison of efficacy of hepatitis B vaccination during induction versus maintenance phase of chemotherapy in acute lymphoblastic leukemia: A nonrandomized clinical trial

Background: Acute lymphoblastic leukemia (ALL) patients are susceptible to hepatitis B infection due to profound immunosuppression and repeated transfusions. However, the comparative effectiveness of hepatitis B vaccination in different phases of chemotherapy has not been studied. Aim: In this comparative interventional study (CTRI/2017/08/009402), vaccination in the induction phase (IP) was compared to that in the maintenance phase (MP). Materials and Methods: The participating ALL patients in both groups (29 per group) were vaccinated with double the dose of hepatitis B vaccine at 0, 1, and 2 months. The proportion of patients with seroprotective anti-hepatitis B surface titers (>10 IU/ml) was compared between the two groups after each dose. Results: The seroprotection rates between both the phases were similar following the first (relative risk [RR] = 4, confidence interval [CI]: 0.47–33.65) and third (RR = 1.4, CI: 0.73-2.84) doses of vaccination, whereas following the second dose of vaccination, the seroprotection rate in IP was significantly higher than that of MP (RR = 1.9, CI: 1.07–3.35). Conclusion: This study concluded that a 0, 1, and 2 schedule of hepatitis B vaccination has similar efficacy in both the IP and the MP of chemotherapy in ALL patients. As the IP has a higher trend of seroprotection rates compared to MP, vaccination in IP followed by revaccination postchemotherapy may be preferred in countries with a high prevalence of hepatitis B infection.

Comparative analysis of the safety and efficacy of HBsAg-1018 versus HBsAg-Eng: a meta-analysis.

IntroductionIn addition to alum adjuvant, a wide diversity of adjuvants have been developed to enhance immune response of hepatitis B virus (HBV) vaccine in varying subjects, either in healthy vaccinators or subjects with hypo-immunity. In this context, a novel HBV vaccine HBsAg-1018, formulated with a toll-like receptor 9 agonist, was developed, and is currently in the phase of clinical trials. So, the first meta-analysis was performed to examine the safety and immune response of HBsAg-1018 among varying subjects.Material and methodsOn the basis of inclusion criterion, eligible studies that reported safety and immunogenicity induced by HBsAg-1018 vaccination in randomised, controlled trials (RCTs) were involved from three databases: PubMed, EMBASE, and the Cochrane Library, and further confirmed by two reviewers. Meta-analysis was conducted using RevMan 5.3. The pooled relative risk (RR) for safety and immunogenicity was calculated using random-effects or fixed-effects models according to the heterogeneity of included studies. The methodology quality of eligible studies was assessed using the Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0.ResultsIn total 5073 subjects administrated with HBV vaccine from four eligible publications were included in this meta-analysis. The data related to immunogenicity and safety post vaccination were pooled for meta-analysis. For safety, the combined RRs for adverse reactions were 0.98 (95% CI: 0.89-1.08), 1.02 (95% CI: 0.94-1.10) for AE, 0.88 (95% CI: 0.70-1.10) for SAE, and 1.07 (0.12-9.17) for death. No statistical heterogeneity among RCTs was found (p > 0.05). For immunogenicity, at four weeks post vaccination, seroprotection rates (SPRs) in HBsAg-1018 were significantly superior to the conventional HBV vaccine containing alum adjuvant, HBsAg-Eng (Engerix-B®, GlaxoSmithKline, Rixensart, Belgium) (RR: 4.35; 95% CI: 3.35-5.65). Furthermore, superior immunogenicity of HBsAg-1018 was maintained with RRs up to 1.23 and 95% CI: 1.20-1.27 through 28 weeks post vaccination. However, there was considerable heterogeneity with > 80% I2 value (p < 0.05).ConclusionsIn comparison with HBsAg-Eng, HBsAg-1018 exhibited superior immune response and comparable safety profile with HBsAg-Eng in varying subjects. HBsAg-1018 is an effective and safe prophylactic measure to prevent HBV infection.

Immunogenicity and side-effects of the inactivated hepatitis A vaccine in periodic fever, aphthous stomatitis, pharyngitis, and adenitis patients.

The aim of this study was to compare the immunogenicity and side-effects of hepatitis A virus (HAV) vaccination between periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) patients and healthy controls who have not been previously exposed to HAV. A prospective observational study was carried out of 28 PFAPA patients and 76 controls who received two doses of the vaccine. Immunogenicity was expressed as seroconversion and seroprotection rates; mean HAV-immunoglobulin G concentration was measured at 0, 1, 7 and 18months. Side-effects were defined as incidence of adverse events and the effect of vaccination on PFAPA symptoms. All participants were seronegative and seroconverted at 1month. One month after primary vaccination, 92.9% of PFAPA patients and 77.6% of the controls attained seroprotection, while the rates increased to 100% and 96.1%, respectively, 1month after the second dose. Seroprotection rates remained adequate 1year after completion of vaccination. In conclusion, two doses of the inactivated HAV vaccine are well-tolerated and effective in children with PFAPA.

Assessment of seroprevalence against poliovirus among Italian adolescents and adults

ABSTRACTIn 2002, the WHO European Region was declared polio-free. Nonetheless global eradication has not yet been completed and the reintroduction from at risk areas is still possible. This seroprevalence study evaluated samples collected from each Italian region in the 12−50 years old age range to assess protection against Poliovirus (PV) 1, 2 and 3 among subjects immunised with different vaccination schedules. 1073 samples (50.5% females) were examined. WHO standardized microneutralization assay was used. Seroprotection rates were 92.9%, 96.2% and 83.4%, for PV1, PV2 and PV3, respectively. Geometric Mean Titres (GMTs) were higher for PV2 (52.8) and PV1 (41.1) than for PV3 (21.0). Increasing the age, a decreasing trend in seropositivity was observed, in particular for PV3. The 2017–2019 Italian National Immunisation Plan emphasises, as primary objective, the maintenance of the polio-free status and strongly validates the 2 + 1 schedule in the first year of life with IPV vaccine associated with the administration of booster doses at 6 years and during the adolescence. Surveillance system and high population immunity are crucial to ensure the maintenance of polio-free status.

Immunogenicity of inacitivated quadrivalent influenza vaccine in adults aged 18-64 years: A systematic review and Meta-analysis

Objective: To evaluate the immunogenicity of inactivated quadrivalent influenza vaccine (QIV) in adults aged 18-64 years, through a Meta-analysis. Methods: Literature was retrieved by searching the Medline, Cochrane Library, Science Direct in the past decade. All the studies were under random control trial (RCT) and including data related to immunogenicity which involving sero-protection rate (SPR) and sero-conversion rate (SCR) of the QIV, versus inactivated trivalent influenza vaccine (TIV) in the population aged 18 to 64. Revman 5.3 software was employed to manipulate the pooled date of the included literature. Result: A total of 8 studies for the SPR and SCR of the shared strains (two A lineage and one B lineage) were included. There appeared no significant differences in the response rates between the two vaccines. As for QIV versus TIV (B/Yamagata), the pooled RR of the SPR for B/Victoria was 1.28 (95%CI: 1.08-1.51, P<0.05), with the pooled RR of the SCR for B/Victoria as 1.94 (95%CI: 1.50-2.50, P<0.05). For QIV versus TIV (B/Victoria), the pooled RR of the SPR for B/Yamagata as 1.10 (95%CI: 1.02-1.18, P<0.05), and the pooled RR of SCR for B/Yamagata as 1.99 (95%CI: 1.34-2.97, P<0.05). Conclusion: In the population aged 18-64 years, inactivated QIV was equivalently immunogenic against the shared three strains included in the activated TIV while a superior immunogenic effect was noticed in the vaccine strain which did not include the inactivated QIV.

Seroprevalence of measles vaccine antibody response in vertically HIV-infected children, in Morocco

BackgroundThe widespread use of an effective and safe vaccine to measles has substantially decreased morbidity and mortality from this epidemic. Nevertheless, HIV-infected children vaccinated against measles may develop an impaired vaccine response and remain susceptible to this disease. In Morocco, infants are routinely vaccinated against measles, regardless of their HIV serostatus. An evaluation of the immunization of these children may be of paramount importance to implement timely measures aimed at preventing measles transmission.MethodsIn this study, we have enrolled 114 children vaccinated against measles, 50 children prenatally infected with HIV and 64 HIV-uninfected children. For all children, blood samples were taken to measure anti-measles IgG by EIA and CD4 count by flow cytometry. Additionally, HIV viral load was determined by automated real time PCR, for HIV-infected children.ResultsThe seroprotective rate of IgG anti-measles antibodies was significantly lower among HIV-infected children (26%) compared with HIV-uninfected children (73%) (p < 0.001). Within HIV-infected children group, the comparison of variables between children without seroprotective seroconversion to measles and those with seroprotective immunity, displayed that sex and age were not statistically different, p > 0.999 and p = 0.730, respectively. However, CD4 count was lower among children with negative serostatus to measles (23% versus 32%, p < 0.001). Furthermore, viral load was higher, with 2.91 log10 ± 2.24 versus 1.7 log10 ± 1.5 (p = 0.042). Finally, 62% of children with a negative vaccine response to measles were under HAART therapy, versus 92% (p = 0.008).ConclusionThe majority of HIV-infected children vaccinated against measles develop a suboptimal seroprotective titer, and therefore remain at risk for this highly infectious disease. These data in combination with international recommendations, including recent WHO guidance on vaccination of HIV-infected children, suggest there is a need for national measures to prevent these children from measles.

Immune Response Among the Children to Hepatitis B Vaccination: A Community-based Study in Bangladesh

Hepatitis B virus infection is a vaccine preventable infection of liver which remains a key public health burden globally. The development of Anti-HBs titre greater than or equal to 10 IU/L is considered as protective immunity and any titre less than 10 IU/L as non-protective following HBV vaccination. There is no comprehensive and authentic data regarding the immune response even 10 years after the integration of the HBV vaccine in to the EPI programme in Bangladesh and specifically, in Brahmonbaria district. The study was also aimed to assess the long term immune response among HBV vaccinated children. Blood sample from 500 vaccinated children were tested for Anti-HBs, and anti-HBc. Sero negative children were given 1 dose of HBV vaccine as a booster. Samples from booster vaccine were taken one month later and tested for anti Hbs titre. Anti HBs titre was found below protective level in about 46.0% (230/500) participants. Sero-protection rate decreased to 72.2% in 5 to 6 years age group which further decreased to 58.3% in 7 to 9 years age group and increased again to 69.5% in 10 to 12 years age group children. On the other hand, the mean anti Hbs titre was 97.72 IU/L initially and then increased with the increasing of age from 165.40 IU/L to 196.67 IU/L. Breakthrough infection of HBV was seen in 1.2% (6/500) participants measuring by anti HBc which indicated protective efficacy of HBV vaccine was about 98.8% (494/500). Sero negative participants were given a booster dose; 93.6% (131/140) participants showed boosting of mean anti HBs titre upto 804.92 IU/L which was below protective level (&lt;10 IU/L) before booster dose. Anti-HBs titre goes below with the increase of age after vaccination. Most of the participants had immunological memory which will boost antibody titre after any exposure, so routine booster dose is not needed. But non-responder to vaccination should screen after primary vaccination because of chance of breakthrough infection.

Antibody persistence and safety and immunogenicity of a second booster dose nine years after a first booster vaccination with a reduced antigen diphtheria-tetanus-acellular pertussis vaccine (Tdap) in adults

BackgroundOver the last decades, pertussis showed periodic increases in its incidence among adults, despite being a vaccine-preventable disease. MethodsThis phase III, multicenter, extension study (NCT00489970) was conducted in adults from the United States, followed at Year (Y) 5 and Y9 post-vaccination with a dose of reduced-antigen-content tetanus-diphtheria-acellular pertussis vaccine containing either 3 (Tdap-B group) or 5 pertussis components (Tdap-A group). Willing participants in Tdap groups and newly-recruited participants (Control group) received one Tdap-B dose at Y9. Antibody persistence (at Y5 and Y9) and safety of Tdap-B at Y9 were assessed. Non-inferiority of immune response elicited by 2 Tdap doses was evaluated at Y9: (i) versus one Tdap-B dose for diphtheria and tetanus in terms of seroprotection rates; (ii) for all antigens in terms of booster response rates (Tdap-B and Tdap-A groups versus Control group); and (iii) for pertussis antigens in terms of geometric mean concentrations (GMCs) versus a 3-dose series of a combined diphtheria-tetanus-acellular pertussis vaccine (DTPa) administered during infancy. Results1257 participants were enrolled at Y5 and 809 participants were vaccinated at Y9. Seroprotection rates in both Tdap groups were ≥98.4% and ≥98.0% (Y5) and ≥98.3% and ≥98.1% (Y9) for diphtheria and tetanus, respectively. For pertussis antigens, antibody concentrations above assay cut-offs were observed for ≥76.6% (Y5) and ≥84.9% (Y9) of participants in Tdap groups. At Y9, one month post-Tdap vaccination, comparable seroprotection/seropositivity rates and antibody GMCs were observed among groups. Non-inferiority of immune responses in both Tdap groups was demonstrated when compared to the Control group for diphtheria and tetanus and to a 3-dose DTPa series for pertussis antigens. Non-inferiority criteria in terms of booster response were not met for all antigens. No safety concerns were raised. ConclusionA second dose of Tdap-B administered in adults, 9 years after initial Tdap vaccination, is immunogenic and well-tolerated.

Antibody Persistence up to 3 Years After Primary Immunization With Inactivated Japanese Encephalitis Vaccine IXIARO in Philippine Children and Effect of a Booster Dose.

An inactivated Vero cell culture derived Japanese encephalitis virus vaccine (IXIARO) requires a booster dose 1 year after primary schedule for long-term antibody persistence in adults. The aim of this study is to evaluate immunogenicity and safety of a booster dose in children 2 months to <18 years of age. This is a randomized, controlled open-label study in the Philippines. Three hundred children vaccinated with IXIARO in a previous trial were randomized 1:1 to receive either no booster or a booster 12 months after initiation of the primary series. Neutralizing antibody titers were assessed before and after the booster and up to 3 years after primary series. Safety endpoints included the rate of subjects with solicited adverse events (AEs), unsolicited AEs and serious AEs within 1 month after the booster. Geometric mean titer declined by 1 year after the primary series, but titers remained above the established protective threshold in 85%-100% of children depending on age group. The booster led to a pronounced increase in geometric mean titer and 100% seroprotection rate in all age groups. The booster was well tolerated, with AE rates lower compared with the primary series. Most AEs were mild. A booster dose of IXIARO administered 12 months after the primary immunization was well tolerated and highly immunogenic.

Non-interference of Bovine-Human reassortant pentavalent rotavirus vaccine ROTASIIL® with the immunogenicity of infant vaccines in comparison with a licensed rotavirus vaccine

BackgroundA newly developed bovine-human reassortant pentavalent vaccine (BRV-PV, ROTASIIL®) was tested for its potential effect on the immunogenicity of concomitantly administered EPI vaccines in infants in a randomized controlled study in India. MethodsIn this Phase III, multicenter, open label, randomized, controlled study, three doses of BRV-PV or two doses of Rotarix® and one dose of placebo were given to healthy infants at 6, 10, and 14 weeks of age. Subjects also received three doses of DTwP-HepB-Hib (diphtheria, tetanus, whole-cell pertussis, hepatitis B, and haemophilus influenzae type b conjugate – pentavalent vaccine) and oral polio vaccine concomitantly at 6, 10, and 14 weeks of age and a single dose of inactivated polio vaccine at 14 weeks of age. Blood samples were collected four weeks after the final vaccination to assess immune responses to all the vaccines administered. For diphtheria, tetanus, hepatitis B, Hib, polio type 1, and polio type 3 antibodies, non-interference was to be supported if the lower limit of the two-sided 90% confidence interval (CI) for the seroprotection rate difference for the BRV-PV group minus the Rotarix® group was >10.0%. For pertussis antibodies, non-interference was to be supported if the lower limit of the two-sided 90% CI for the ratio of geometric mean concentrations (GMCs) was >0.5. ResultsA total of 1500 infants were randomized to either BRV-PV (1125 infants) or Rotarix® (375 infants), of which 1341 completed the study as per the protocol. More than 97% of subjects achieved seroprotective antibody titres against diphtheria, tetanus, hepatitis B, Hib, polio type 1, and polio type 3 in both groups. The difference in seroprotection rates between the BRV-PV group and the Rotarix® group for all these antibodies was less than 1%. The ratio of GMCs of anti-pertussis IgG concentrations for the BRV-PV group versus Rotarix® was 1.04 [90% CI: 0.90; 1.19]. ConclusionBRV-PV does not interfere with the immunogenicity of concomitantly administered routine infants vaccines.

Aluminum salts as an adjuvant for pre-pandemic influenza vaccines: a meta-analysis

Avian-origin H5/H7 influenza has the potential to cause the next influenza pandemic. Availability of effective vaccines is an essential part of pre-pandemic preparedness. However, avian influenza surface antigens are poorly immunogenic to humans, which necessitates the use of adjuvants to augment the immunogenicity of pre-pandemic influenza vaccines. Aluminum salts are approved, safe, and affordable adjuvants, but their adjuvanticity for influenza vaccines remains unverified. We conducted the first meta-analysis on this issue. A total of nine randomized controlled trials (2006–2013, 22 comparisons, 2,467 participants in total) compared aluminum-adjuvanted H5N1 vaccines versus non-adjuvanted counterparts. The weighted estimate for the ratio of the seroprotection rate after a single dose of H5N1 vaccine is 0.66 (95% CI: 0.53 to 0.83) by hemagglutination-inhibition assay or 0.56 (95% CI: 0.42 to 0.74) by neutralizing titer assay. The weighted estimate for the risk ratio of pain/tenderness at injection sites is 1.85 (95% CI: 1.56 to 2.19). The quality of evidence is low to very low for seroprotection (due to indirectness and potential reporting bias) and moderate for pain/tenderness (due to potential reporting bias), respectively. The significantly lower seroprotection rate after aluminum-adjuvanted H5N1 vaccines and the significantly higher risk of pain at injection sites indicate that aluminum salts decrease immunogenicity but increase local reactogenicity of pre-pandemic H5N1 vaccines in humans.

Prospective cohort studies to evaluate the safety and immunogenicity of the 2013, 2014, and 2015 seasonal influenza vaccines produced by Instituto Butantan.

ABSTRACTAnnual vaccination is the most effective way to prevent seasonal influenza illness. Instituto Butantan (IB) performed clinical studies with its 2013, 2014 and 2015 seasonal trivalent influenza vaccines (inactivated split-virion). Prospective cohort studies were carried out to describe the safety and immunogenicity of Instituto Butantan influenza vaccines, in healthy adults and elderly, from 2013 to 2015. Immediately after the informed consent was signed, participants underwent blood collection followed by vaccination. On study days 1, 2 and 3 post-vaccination participants were contacted by the staff to evaluate the occurrence of solicited (local and systemic) and non-solicited adverse reactions. On study day 21 (+7) subjects returned to the clinical site for final safety assessments and blood collection to evaluate post-vaccination immunogenicity. The immunogenicity analyses were performed by means of hemagglutination inhibition (HI) assay. The immunogenicity endpoints were: seroprotection (SPR) and seroconversion (SCR) rates and the geometric mean HI antibody titer ratio (GMTR). The 2013 study was conducted at the Centro de Referência para Imunobiológicos Especiais (CRIE) and at the Centro de Pesquisa Clínica do Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo while the 2014 and 2015 studies were conducted at CRIE. The vaccine composition followed the WHO recommendation for the Southern hemisphere seasonal influenza vaccine. Forty-seven healthy adults and 13 elderly participated in the 2013 study, 60 healthy adults and 60 elderly in the 2014 study, and 62 healthy adults and 57 elderly in the 2015 study. In the 2013, 2014 and 2015 studies, pain was the most frequent local adverse reaction and headache the most frequent systemic adverse reaction. All observed adverse reactions were classified as mild or moderate and none as severe. SPR >70% and SPR >60% were observed in adults and elderly, respectively, for the three vaccine viruses, in the 2013, 2014 and 2015 studies. SCR >40% was observed in adults, for the three vaccine viruses, only in the 2014 study and SCR >30% was observed in the elderly, for the three vaccine viruses, only in the 2013 and 2014 studies. GMTR >2.5 among adults, for the three vaccine viruses was only observed in the 2013 study and GMTR >2.0 was observed among elderly, for the three vaccine viruses, in the 2013, 2014 and 2015 studies. The 2013, 2014 and 2015 seasonal influenza vaccines produced by Instituto Butantan were safe and immunogenic according to the immunogenicity criteria defined by the European Medicines Agency (EMA).

Immunogenicity and predictors of response to a single dose trivalent seasonal influenza vaccine in multiple sclerosis patients receiving disease-modifying therapies.

To evaluate the immunogenicity and safety of a seasonal influenza vaccine in a cohort of multiple sclerosis (MS) patients receiving different immunomodulating/immunosuppressive therapies and assess predictors of immune response. A prospective, multicenter, non-randomized observational study including 108 patients receiving a trivalent seasonal influenza vaccination was conducted. Influenza-specific antibody titers (H1N1, H3N2, and influenza B) were measured to evaluate rates of seroprotection and seroconversion/significant titer increase. Univariable and multivariable analyses were performed to identify prognostic factors of vaccination outcomes. Regarding the whole cohort, seroprotection rates >70% were achieved for each influenza strain. Interferon-treated patients reached high seroprotection rates (>84%). Good seroprotection rates were seen in patients treated with glatiramer acetate. In particular for H3N2, response rates were low in natalizumab-treated patients and in the small subgroup of fingolimod-treated patients. Patients with a previous disease-modifying therapy and a longer disease duration were less likely to respond sufficiently. No severe adverse events were reported. MS disease activity was not increased after a one-year follow-up period. Vaccination led to good immunogenicity, especially in MS patients treated with interferons and glatiramer acetate. At least for the H1N1 strain, rates of seroprotection and seroconversion/significant titer increase were high (>70% and >60%, respectively) for all therapeutic subgroups. Patients with a longer duration of the disease are exposed to an increased risk of insufficient immune response to vaccination.

A Safety and Immunogenicity Study of a Single Dose of a Meningococcal (Groups A, C, W, and Y) Polysaccharide Diphtheria Toxoid Conjugate Vaccine (MEN-ACWY-D) in Healthy Japanese Participants

Meningococcal disease can cause significant disability and mortality. The quadrivalent meningococcal polysaccharide diphtheria toxoid conjugate vaccine (Men-ACWY-D) protects against invasive meningococcal disease caused by serogroups A, C, W, and Y. This phase III, open-label, single-arm, multicenter study evaluated the safety and immunogenicity of a single vaccine dose in healthy Japanese adults. The study enrolled 200 participants between 2 and 55 years of age. Immunogenicity was assessed by quantifying the seroprotection rates (the proportion of participants with antibody titers ≥ 1:128 against the capsular polysaccharide from all 4 serogroups measured 28 days after vaccination). Safety endpoints included occurrence, nature, time to onset, duration, intensity, relationship to vaccination, and outcome of solicited and unsolicited adverse events (AEs) and serious AEs (SAEs). Participants included 194 adults, 2 adolescents, and 4 children. Among adults, the seroprotection rates for serogroups A, C, W, and Y were 91.2%, 80.2%, 89.1%, and 93.8%, respectively. Seroconversion rates (the proportion of participants with pre-vaccination titers of < 1:4 and a ≥ 4-fold rise from baseline) were 87.3%, 83.0%, 94.4%, and 96.4%, respectively. No immediate AEs, adverse reactions, SAEs, or deaths were reported for any age group. Men-ACWY-D is well tolerated and immunogenic, eliciting antibodies against capsular polysaccharides from all 4 serogroups in Japanese adults.

HBsAg-1018, a Two-Dose Hepatitis B Vaccine, Is Well Tolerated and Effective in Diabetic Patients Aged 60 Years or Older

Background: Adult patients with diabetes mellitus (DM) have a greater risk of contracting hepatitis B virus (HBV) than the general population, including those ≥ 60 years of age. When infected, patients with DM have more severe HBV-related morbidity and accelerated progression. The CDC recommends HBV vaccination of all adults with DM who are ≥ 60 years of age at the discretion of the treating physician. Due to persistent challenges, including hyporesponsiveness with current 3-dose vaccines, 87% of individuals with DM who are ≥ 60 years of age remain unvaccinated. HBsAg-1018 (Heplisav-BTM) is a 2-dose HBV vaccine with demonstrated higher protection rates than a 3-dose vaccine, particularly in populations known to be hyporesponsive. In this post-hoc analysis of a phase 3 trial, we assessed the safety and efficacy of HBsAg-1018 in patients with type 2 DM (T2DM) who were ≥ 60 years of age. Methods: Patients with T2DM and who were 60-70 years old received either 2-dose HBsAg-1018 at 0 and 4 weeks and placebo at 24 weeks or 3-dose HBsAg-Eng (Engerix-B®) at 0, 4, and 24 weeks. Peak (week 24, HBsAg-1018 vs. week 28, HBsAg-Eng) seroprotection rates (SPRs) and safety were assessed by subgroups (sex, body mass index [BMI], and smoking status). Results: A total of 480 patients (HBsAg-1018, n=327; HBsAg-Eng, n=153) were included in this analysis. Among patients who received all study injections, the peak SPR was significantly higher with HBsAg-1018 at week 24 (88.2% [231/262]) than with HBsAg-Eng at week 28, giving an overall difference of 29.7% (95% CI: 20.5, 39.1; P&amp;lt;.0001). SPRs with HBsAg-1018 were significantly higher compared with HBsAg-Eng regardless of sex, BMI, or smoking status (P ≤ .01). Adverse events, serious adverse events, and deaths were comparable between HBsAg-1018 and HBsAg-Eng. Conclusion: Two-dose HBsAg-1018 provides better protection against HBV than a 3-dose vaccine (HBsAg-Eng) with a similar safety profile in patients ≥ 60 years of age with T2DM regardless of subgroup. Disclosure R.N. Hyer: Employee; Self; Dynavax Technologies. R.S. Janssen: Employee; Self; Dynavax Technologies.

IMMUNOGENICITY OF THE THIRD GENERATION HEPATITIS B VACCINE (pre-S1/pre-S2/S)

Currently, second-generation hepatitis B vaccines are widely used. They are produced in biotechnological eukaryotic yeast-based systems and contain the S-protein domain of HBsAg particle in the complete absence of pre-S1 and pre-S2 domains. At the same time, these antigens were proved to significantly influence immunogenicity, which makes the development and use of third-generation vaccines containing all antigenic determinants a long-range objective. A randomized, double-blind clinical study was conducted to compare immunogenicity of second- and third-generation vaccines Engerix-B™ and Sci-B-Vac™, respectively. Healthy subjects of both sexes aged 18 to 45 years (n = 94) who are seronegative for HBsAg, HBsAb, HBcAb at screening and who previously had not received immunobiological agents for hepatitis B prophylaxis were included in the study. Group I (n = 47) received the second-generation vaccine Engerix-B™, Group II (n = 47) — the third-generation vaccine Sci-B-Vac™. Subjects received vaccines three times — on days 1, 28 and 180 of the study. HBsAb levels, rates of seroconversion (the proportion of subjects with HBsAb levels 2.1 mIU/mL) and seroprotection (the proportion of subjects with HBsAb levels ≥ 10 mIU/mL) were assessed on days 28, 90, 180 and 210 of the study. Early seroconversion rate assessed on Day 28 was 76.60% in Group I and 93.88% in Group II (p 0.05); seroprotection rate was 51.06 and 61.22%, respectively. These differences in the proportion of subjects who achieved seroconversion on Day 28 may indicate a faster immunological response to Sci-B-Vac™ vaccine. Statistically significant differences between the level of antibodies on days 90 and 180 (p 0.05) were observed when analyzing the average values of HBsAb concentration in Groups I and II. The concentration of HBsAb on Day 90 was 378.68±60.95 mIU/mL in Group I, and 618.31±58.34 mIU/mL in Group II. On Day 180, the concentration of HBsAb reached 441.34±63.83 mIU/mL in Group I, and 757.72±55.14 mIU/mL in Group II. The significance of dependence of antibody level on sex, age and body weight was analyzed. It was revealed that the age of a vaccinated subject affects antibody level after administration of Engerix-B™ (p 0.05). The results obtained suggest that there is a rapid and strong immune response to the third-generation vaccine Sci-B-Vac™. This may indicate advantage of the vaccine containing all three recombinant proteins of hepatitis B virus envelope, which, in turn, can play a key role in clinical practice for urgent prophylaxis of hepatitis B, as well as for treatment of immunocompromised conditions.

Immune response to the hepatitis B antigen in the RTS,S/AS01 malaria vaccine, and co-administration with pneumococcal conjugate and rotavirus vaccines in African children: A randomized controlled trial

ABSTRACTThe RTS,S/AS01 malaria vaccine (Mosquirix) reduces the incidence of Plasmodium falciparum malaria and is intended for routine administration to infants in Sub-Saharan Africa. We evaluated the immunogenicity and safety of 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV; Synflorix) and human rotavirus vaccine (HRV; Rotarix) when co-administered with RTS,S/AS01 (www.clinicaltrials.gov NCT01345240) in African infants. 705 healthy infants aged 8–12 weeks were randomized to receive three doses of either RTS,S/AS01 or licensed hepatitis B (HBV; Engerix B) vaccine (control) co-administered with diphtheria-tetanus-acellular pertussis-Haemophilus influenzae type-b-conjugate vaccine (DTaP/Hib) and trivalent oral poliovirus vaccine at 8–12-16 weeks of age, because DTaP/Hib was not indicated before 8 weeks of age. The vaccination schedule can still be considered broadly applicable because it was within the age range recommended for EPI vaccination. PHiD-CV or HRV were either administered together with the study vaccines, or after a 2-week interval. Booster doses of PHiD-CV and DTaP/Hib were administered at age 18 months.Non-inferiority of anti-HBV surface antigen antibody seroprotection rates following co-administration with RTS,S/AS01 was demonstrated compared to the control group (primary objective). Pre-specified non-inferiority criteria were reached for PHiD-CV (for 9/10 vaccine serotypes), HRV, and aP antigens co-administered with RTS,S/AS01 as compared to HBV co-administration (secondary objectives). RTS,S/AS01 induced a response to circumsporozoite protein in all groups. Pain and low grade fever were reported more frequently in the PHiD-CV group co-administered with RTS,S/AS01 than PHiD-CV co-administered with HBV. No serious adverse events were considered to be vaccine-related. RTS,S/AS01 co-administered with pediatric vaccines had an acceptable safety profile. Immune responses to RTS,S/AS01 and to co-administered PHiD-CV, pertussis antigens and HRV were satisfactory.

Immunogenicity, safety, and tolerability of a recombinant hepatitis B vaccine manufactured by a modified process in healthy young Japanese adults

ABSTRACTHepatitis B vaccines are highly effective in preventing hepatitis B virus infection and have been included in the national immunization program of Japan since 2016. Heptavax®-II is one of two hepatitis B vaccine products licensed in Japan, and its manufacturing process is being modified to reduce variability of manufacturing and optimize immunogenicity. In this study (NCT01463683), the immunogenicity and safety of a modified-process hepatitis B vaccine (mpHBV) were compared to those of the licensed Heptavax®-II. Overall, 722 Japanese adults aged 20-to-35 years old were randomized in a 3:3:1 ratio to either the mpHBV subcutaneous (SC) injection group (mpHBV SC), the Heptavax®-II SC injection group (Heptavax®-II SC), or the mpHBV intramuscular (IM) injection group (mpHBV IM). All participants received a 3-dose series of either mpHBV or Heptavax®-II at Day 1, Month 1, and Month 6. Serum antibody to hepatitis B virus surface antigen (anti-HBs) was assayed on Day 1 prior to the first vaccination and Month 7 (1 month Postdose 3). Seroprotection rates in mpHBV SC were non-inferior to that in Heptavax®-II SC and anti-HBs geometric mean titers were numerically higher in mpHBV SC as compared to Heptavax®-II SC. The incidences of injection-site and systemic adverse events (AEs) observed in mpHBV SC were comparable to those in Heptavax®-II SC, except for erythema which was higher in mpHBV SC than in Heptavax®-II SC. Most injection-site and systemic AEs were mild-to-moderate in intensity and there were no reports of vaccine-related serious AEs in any group. IM administration of mpHBV was well-tolerated and more immunogenic compared to SC administration. In conclusion, mpHBV and Heptavax®-II were well-tolerated and elicited satisfactory immune responses for the prevention against hepatitis B virus-associated diseases.

Safety of a two-dose investigational hepatitis B vaccine, HBsAg-1018, using a toll-like receptor 9 agonist adjuvant in adults

BackgroundHepatitis B virus infection remains an important global public health problem. Approved alum-adjuvanted vaccines are well tolerated but require three doses and have reduced immunogenicity in adults. A two-dose vaccine containing hepatitis B surface antigen combined with a novel, Toll-like receptor 9 agonist adjuvant (HBsAg-1018 [HEPLISAV–B®]) has demonstrated significantly higher seroprotection rates than a three dose vaccine. MethodsA post hoc analysis compared the safety of HBsAg-1018 with HBsAg-Eng (Engerix-B®), in three randomized, observer-blinded, active-controlled, multi-center phase 3 trials in adults. HBsAg-1018 was administered intramuscularly at weeks 0 and 4 and placebo at week 24 and HBsAg-Eng at weeks 0, 4, and 24. ResultsPost-injection reactions, adverse events, medically attended adverse events, and new-onset immune-mediated adverse events were balanced between vaccine groups. Anti-nuclear antibodies, anti-double stranded DNA antibodies, anti-neutrophil cytoplasmic antibodies, and antiphospholipid antibodies were balanced between groups. A transient increase in anti-beta2 glycoprotein 1 IgM was observed in the HBsAg-1018 group but was not associated with a thrombotic event. Serious adverse events and deaths were generally balanced between groups. ConclusionHBsAg-1018 had a similar safety profile to HBsAg-Eng. With improved immunogenicity and fewer doses over a shorter time, HBsAg-1018 has the potential to provide improved seroprotection and a significant public health benefit to adults 18 years of age or older.