An adjuvant compound that enhances immunogenicity at fractional doses of the Sabin-inactivated poliovirus vaccine (sIPV) with a long duration of protection in a rat model.

BACKGROUND: At the same dosage, the new generation of Sabin-inactivated poliovirus vaccine (sIPV) is less immunogenic than the traditional oral polio vaccine (OPV) dosage in China. The useful adjuvant might be a necessary strategy to strengthen the immune protective effects. METHODS: In this study, we produced an adjuvant compound (named KML05) that could promote immunogenicity and fractional doses of sIPV with a long duration of protection in a rat model. The compound adjuvant had both advantages and a function of MF59 and carbopol971P. RESULTS: The effect seroconversion of experimental animals immunized with KML05 could be extended to one-eighth of the dose. According to the result of the geometric mean titers (GMTs), KML05 adjuvant could save eight times the amount of sIPV D-antigen usage, but aluminum hydroxide adjuvant could save twice at the same titers. Additionally, it was found that there was a significant difference in the GMT titer of poliovirus type 2 between animals immunized by KML05 and alum adjuvant (P < 0.05). At 12th-month postvaccination, the neutralization titers stimulated by IPV-KML05 were maintained over a longer time period in immunized animals. CONCLUSION: Our research team developed KML05 adjuvant, which combined carbopol971P with MF59, increased antibody responses to sIPV for a longer duration of protection in a rat model.

A prospective, single-arm, open-label, non-randomized, phase IIa trial of a nonavalent prophylactic HPV vaccine to assess immunogenicity of a prime and deferred-booster dosing schedule among 9-11 year-old girls and boys - clinical protocol.

BACKGROUND: Human papillomavirus (HPV) vaccines are indicated for the prevention of cancers and genital warts caused by vaccine-covered HPV types. Although the standard regimen requires a two or three-dose vaccine series, there is emerging data suggesting that a single dose of the bivalent or quadrivalent HPV vaccine generates persistently positive antibody titers. No similar data is yet available for the nonavalent HPV vaccine, currently the only HPV vaccine available in the United States. The overall objective of our study is to assess the stability and kinetics of antibody titers for 24 months following a single dose of the nonavalent HPV vaccine among preteen girls and boys. METHODS: This is a prospective, single-arm, open-label, non-randomized, Phase IIa trial among 9-11 year-old girls and boys to determine the immunogenicity after a single dose of the nonavalent HPV vaccine (GARDASIL® 9) over 24 months, with a deferred booster dose at 24 months and an optional booster at 30 months after the first dose. Participants provide blood specimens at 6, 12, 18, 24, and 30 months after the first dose. Serologic geometric mean titers (GMT) of the nine vaccine types (HPV 16/18/ 6/11/31/33/45/52/58) will be measured at each time point. The primary objective is to determine the stability of type-specific serologic GMT of HPV16 and HPV18 between the 6- vs. 12-month, 12- vs. 18-month, and 18- vs. 24-month visits. Secondary objectives are to determine the stability of type-specific serologic GMT of the other HPV types (HPV 6/11/31/33/45/52/58) between the visits and to assess safety and reactogenicity after each vaccine dose. DISCUSSION: Single dose HPV vaccination could simplify the logistics and reduce costs of HPV vaccination in the US and across the world. This study will contribute important immunogenicity data on the stability and kinetics of type-specific antibody titers and inform feasibility of the single dose HPV vaccination paradigm. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02568566 . Registered on October 6, 2015.

Development and evaluation of vaccine against Staphylococcus aureus recovered from naturally occurring mastitis in she-camels.

The predominant Staphylococcus aureus (S. aureus), an etiological agent of camel mastitis is becoming drug resistant that invites prevention and control strategies. Vaccine production would have a valuable impact on public health. Therefore, in present study, inactivated vaccine with different adjuvants was prepared and evaluated against S. aureus. The vaccinal isolate recovered from camel subclinical mastitis was coagulase positive (PCR based), having expressed pseudocapsule, holding alpha-beta hemolysin characteristics, and multiple drug resistant. Inactivated alum precipitated S. aureus vaccine (APSV) and oil adjuvant S. aureus vaccine (OASV) were prepared after confirming its antigenicity in rabbits. Three groups of rabbits were randomly inoculated with APSV, OASV, and placebo (Unvaccinated, UV). Each group was further divided into two groups based on single and booster dose inoculation. Booster dose of vaccines in rabbits at day 15th of primary inoculation was given. Serum samples were taken on 15, 30, 45 and 60 days of primary inoculation from all rabbits. Analysis of variance was applied to compare geometric mean titer (GMT) of three groups, while t-test was applied to estimate the difference between single and booster dose response. The study found 1010 CFU/mL S. aureus as standard bacterial load for vaccines with higher and sustained antigenicity. The vaccines were safe from morbidity and mortality, and proved effective and stable for 7 and 4 months at 25 °C and 37 °C, respectively. The OASV produced significantly (p < 0.05) higher immune response followed by APSV throughout trial. The highest GMT by APSV and OASV vaccines with single dose inoculation was 37.92 and 69.92 at day 45th post primary inoculation, respectively. Similarly, 59.20 and 142.40 GMTs were noted with booster dose in case of APSV and OASV, respectively. The booster dose presented significantly (p < 0.05) higher GMT than that of single dose inoculation of vaccines. The study concluded APSV and OASV safe, effective, and stable with significant immunogenic results in experimental rabbits.

Cost-Effectiveness of Pneumococcal Vaccination in Adults in Italy: Comparing New Alternatives and Exploring the Role of GMT Ratios in Informing Vaccine Effectiveness.

In Italy, a sequential pneumococcal vaccination with conjugate vaccine (PCV) and polysaccharide vaccine (PPSV23) is recommended for individuals aged ≥ 65 years and those at risk for pneumococcal disease (PD) aged ≥ 6 years. The aim of this study was to assess the cost-effectiveness of the new vaccines, i.e., approved 15-valent and 20-valent PCVs. A published Markov model was adapted to evaluate the lifetime cost-effectiveness of vaccination with PCV15 + PPSV23 versus PCV13 + PPSV23, PCV20 alone, PCV20 + PPSV23, and No Vaccination. Simulated cohorts representing the Italian population, including individuals aged ≥ 65 years, those at risk aged 50-100 years, and those deemed high risk aged 18-100 years were assessed. Outcomes were accrued in terms of incremental PD cases, costs, quality-adjusted life years, life years, and the cost-utility ratio relative to PCV13 + PPSV23. The conservative base case analysis, including vaccine efficacy based on PCV13 data, showed that sequential vaccination with PCV15 or PCV20 in combination with PPSV23 is preferred over sequential vaccination with PCV13 + PPSV23. Especially in the high-risk group, PCV15 + PPSV23 sequential vaccination was dominant over No Vaccination and resulted in an ICUR of €3605 per QALY gained. Including PCV20 + PPSV23 into the comparison resulted in the domination of the PCV15 + PPSV23 and No Vaccination strategies. Additionally, explorative analysis, including the geometric mean titer (GMT) informed vaccine effectiveness (VE) was performed. In the low-risk and high-risk groups, the results of the GMT scenarios showed PCV15 + PPSV23 to be dominant over the other sequential vaccines. These findings suggest that if real-world studies would confirm a difference in vaccine effectiveness of PCV15 and PCV20 versus PCV13 based on GMT ratios, PCV15 + PPSV23 could prove a highly immunogenic and effective vaccination regime for the Italian adult population.

Increasing serum antibodies against type B influenza virus in 2017-2018 winter in Beijing, China.

Influenza B virus circulates yearly with lower activity than that of influenza A virus in China. During winter 2017 to 2018, a sharp surge of influenza activity dominated by type B/Yamagata lineage virus caused unprecedented medical burden in Beijing. This research aimed to understand the underlying mechanism for this circulation and prepare for epidemics in the future. Sera samples collected from the patients in 2016-2017 and 2017-2018 flu seasons were tested for profiling hemagglutinin inhibition (HI) antibodies against both prevailing Victoria and Yamagata lineages of type B influenza viruses. It showed that the seroprevalence against both lineages of the virus in 2017-2018 winter was higher than that in 2016-2017, while no difference of the seroprevalence was observed between the two viruses. Meanwhile, significant elevated geometric mean titer (GMT) against both lineages of influenza B viruses was found in the specimens collected during 2017-2018 flu season than that from 2016 to 2017, suggesting the viruses might undergo antigenic changes. These results also suggested that lower GMT against both type B variants in 2016-2017 might serve as an immunological niche for the dominating of B/Yamagata virus in China during 2017-2018 winter season. Our findings have implication that there was a significantly elevation of HI antibodies to influenza viruses B in 2017-2018 than in 2016-2017. On the other hand, the low level of HI antibodies to both B/Y and B/V in 2016-2017 could contribute to the severe B/Y epidemic in 2017-2018 to some extent.

Safety and immunogenicity of a single dose, live-attenuated 'tetravalent dengue vaccine' in healthy Indian adults; a randomized, double-blind, placebo controlled phase I/II trial.

BACKGROUND: Dengue fever is the most prevalent mosquito-borne viral disease in the world, with 390 million dengue infections occurring every year. There is an unmet medical need to develop a safe, effective and affordable dengue vaccine against all four Dengue serotype viruses-DENV1, DENV-2, DENV-3 and DENV-4. Panacea Biotec Ltd (PBL) has developed a cell culture-derived, live-attenuated, lyophilized Tetravalent Dengue Vaccine (TDV). Here, in phase I/II study we assessed the safety and immunogenicity of single dose 'Dengue Tetravalent Vaccine' in healthy Indian adults. METHODS: In the study, 100 healthy adult volunteers aged 18-60 years were enrolled. The participants were allocated to TDV and placebo groups in 3:1 ratio, i.e. 75 participants to TDV group and 25 participants to the placebo group. Enrolled participants were administered a single dose of 0.5 ml of the test vaccine / placebo by subcutaneous route. Primary outcome for safety included all solicited AEs up to 21 days, unsolicited AEs up to 28 days and all AEs/serious adverse events (SAEs) till day 90 post-vaccination. For immunogenicity assessment the primary outcome was seroconversion & seropositivity rate by PRNT50 to all four serotype till 90 days. RESULTS: Overall, 100 subjects were vaccinated out of which 8 subjects (5 subjects in vaccine group and 3 subjects in placebo group) dropped out from the study. The most commonly reported solicited local AE was pain and most common solicited systemic AE was headache and fever. No SAE was reported during the study. There was no statistically significant difference between TDV and placebo groups in terms of AEs. Of the 92 subjects who completed all scheduled visits in the study, 59 (81.9%) achieved seroconversion for DENV-1, 56 (77.8%) for DENV-2; 59 (81.9%) for DENV-3 and 57 (79.2%) for DENV-4 in TDV group. The seroconversion rate in the TDV group was statistically significant (p < 0.001) compared to placebo.Clinical trial registration: CTRI/2017/02/007923.

Predictive effect of five hepatitis B virus markers on re-vaccination time of hepatitis B vaccine.

Examination of predictive effect of five hepatitis B virus (HBV) markers on the re-vaccination time of hepatitis B vaccine was assessed. A total of 3,243 patients examined by five HBV markers in Women and Children's Health Care Hospital of Linyi from January 2015 to December 2017 were selected as the subjects and analyzed retrospectively. According to the previous time of hepatitis B antibody vaccination, subjects were divided into three groups: Short-term group (previous time of hepatitis B vaccination <5 years, n=798); medium-term group (>5 years - ≤10 years, n=1,242); long-term group (>10 years, n=1,203). The enzyme linked immunosorbent assay was used to qualitatively analyze the five HBV markers, and chemiluminescence immunoassay was used to quantitatively analyze the five HBV markers. Hepatitis B surface antigen (HBsAg) in the long-term group and the medium-term group was significantly lower than that in the short-term group (P<0.001). HBsAg, hepatitis B e antigen, hepatitis B e antibody, hepatitis B core antibody in the long-term group was significantly higher than that in the medium-term and short-term group (P<0.050). The hepatitis B surface antibody in the long-term group was significantly lower than that in the other two groups (P<0.050). According to the previous time of the hepatitis B antibody vaccination, the patients in the long-term group were subdivided into three groups: Group A (vaccination time: 10-13 years, n=420); group B (13-15 years, n=377) and group C (>15 years, n=406). Geometric mean titer in group A was significantly lower than that in the other two groups (P<0.050). In conclusion, the protective effect of hepatitis B antibody vaccine is satisfactory for 10 years after vaccination, and re-vaccination is recommended after more than 13 years of vaccination when the virus begins to increase significantly, in order to prevent the occurrence of hepatitis B.

HPV vaccines: alternative dosage schedules.

Introduction: The randomized control trials (RCTs) that resulted in licensure of HPV VLP vaccines used a traditional prime, prime-boost schedule for a subunit protein vaccine. These vaccines delivered predominantly to 9-14-year-old females with this schedule have been shown to be highly effective against vaccine HPV-type disease (CIN and genital warts) and infection. A two-dose prime-boost schedule is immunologically non-inferior to 3 doses in 9-14-year-olds and is currently widely adopted. However, even with a reduced dosage schedule, these vaccines are expensive to buy and expensive and logistically complex to deliver especially in low resource countries that bear the major burden of cervical cancer the most prevalent of HPV caused cancers.Areas covered: Observational studies and post hoc analysis of RCTs show that 1 dose, although immunologically inferior to 2 and 3 doses, is as effective at preventing persistent infection with vaccine HPV types at least for 7-10 years. To address the issue of alternative dosage schedules that include 1 dose either as a single dose or extended 1 + 1 with the second dose 3-5 years post-first dose are under investigation in RCTs.Expert opinion: Since, in the short term, vaccine supplies are constrained and will impact on the ability of countries to implement HPV vaccine programs: the challenges and opportunities of the alternative approaches in this scenario are discussed.

Long time immunogenicity of measles vaccine in the vaccination era: An open question.

After WHO European Region determined the 2005 - 2010 Strategic Plan for measles elimination, the number of reported measles cases in Europe fell dramatically. This decrease is related to the vaccination strategy carried out by European countries. This extensive immunization strategy changes the epidemiological patter and could influence the effectiveness and the long-time immunogenicity of the vaccine. To evaluate the long-time immunogenicity of the measles vaccine in the vaccination era, a pilot study among vaccinated blood donors in Apulia was designed. Of 174 enrolled patients, 93.7% presented an anti-measles IgG titer positive. GMT seems to increase by age (p = 0.001). The GMT seems to increase by age and this could be related to the exposition to natural boosters, that was more probable before the beginning of universal mass vaccination against measles. Future studies have to focus the correlation between GMT and age.

Safety and effectiveness assessment of 2011-2012 seasonal influenza vaccine produced in China: a randomized trial.

OBJECTIVE: This study evaluated the effectiveness and safety of the egg-based, trivalent, inactivated split influenza vaccine produced by the Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, China. METHODS: From March 2012 through May 2012, we enrolled a total of 1390 healthy volunteers between the ages of 3 and 80 years in a randomized clinical trial at the Hebei Disease Control Center Vaccine Clinical Evaluation Center. For all subjects, body part adverse reactions and whole-body adverse reactions were observed 30 min, 6 h, and 1-7 days' post-inoculation. If no severe adverse effects were observed 7 days' post-vaccination, the local and systemic reactions of preliminary test participants were recorded until day 28. There was no placebo group in this study. Blood samples were taken for serological testing before vaccination and 28 days' post-vaccination. RESULTS: Twenty-eight days after vaccination, the seroconversion rates of experimental and control groups were H1N1 75.3% and 75.7%, H3N2 75.8% and 71.8%, B 70.7% vs. 69.4%, (P > 0.05). The antibody Geometric Mean Titer（GMT）of experimental and control groups were H1N1 (179.7, 182.4), H3N2 (584.0, 445.7), B (201.4,191.6). The protection rate of experimental and control groups was not statistically significant (H1N1: 86% vs. 87%, H3N2: 99% vs. 98%, B: 98% vs. 98%). Also, 95% confidence intervals of the protection rate difference between the experimental and the control group were H1N1: -0.1% (-4.1,3.8) %, H3N2: 0.3% (-1.0,1.7) % and B: 0.2% (-1.5,1.9) %; confidence intervals exceeded the limit of -5%. The rates of adverse reactions between experimental and control groups were 6.3% and 7.7% in local response reactions, and 19.5% and 18.0% in systemic reactions. Three hundred and twenty-seven adverse events (AEs) in 1200 (27.76%) subjects were reported within 28 d after vaccination. No serious adverse events occurred during the study. CONCLUSIONS: The experimental vaccine three-antibody protection rate was non-inferior to the control vaccine. Our results demonstrated that the experimental vaccine achieved the primary immunogenic end point of the intended clinical protocol, as well as a secondary immunogenic end-point, with an acceptable level of safety. IRB approval for this study was issued under #2012Y0005 and registered as Clinical Trial No. NCT01551810.

Postdose 3 G1 serum neutralizing antibody as correlate of protection for pentavalent rotavirus vaccine.

Although clinical trials of the pentavalent rotavirus vaccine (RotaTeq®, RV5) have demonstrated efficacy against RV gastroenteritis (RGE) in low and high-income settings, a clear correlate of protection or a measure of immune response that could predict efficacy has yet to be identified. This is the first time that immunogenicity data with both serum neutralized antibody (SNA) titers and anti-RV IgA titers from several clinical efficacy trials were pooled to provide a unique context for evaluating the correlation between immunogenicity and RGE risk or efficacy of RV5. The correlation between immunogenicity and RGE risk is evaluated with data at the individual subject level. The analyses show that higher Postdose 3 (PD3) G1 SNA titers are associated with lower odds of contracting any RGE. The correlation between immunogenicity and efficacy is assessed using aggregated population level data, which shows higher efficacy associated with higher PD3 G1 SNA geometric mean titer (GMT) ratio (between RV5 and placebo) and PD3 serum anti-RV IgA GMT ratio. Among high-income countries, efficacy plateaus over the range of PD3 G1 SNA GMT ratios and PD3 serum anti-RV IgA GMT ratios. From both individual- and population-level analyses, PD3 G1 SNA titers correlated most closely with the RGE risk or efficacy for RV5.

Efficacy and safety of vi-tetanus toxoid conjugated typhoid vaccine (PedaTyph™) in Indian children: School based cluster randomized study.

Vi polysaccharide typhoid vaccines cannot be used in children <2 years owing to poor immunogenic and T cell independent properties. Conjugate vaccine prepared by binding Vi to tetanus toxoids (Vi-TT) induces protective levels even in children <2 years. We evaluated efficacy and safety following vaccination with a Vi-TT vaccine in children 6 months to 12 years of age. Overall, 1765 subjects were recruited from two registered municipal urban slums of southern Kolkata. Most of the children of the slum dwellers attended the schools in the locality which was selected with permission from the school authority. Schools were randomly divided into vaccinated (Test group) and unvaccinated group (Control group). Children and their siblings of test group received 2-doses of PedaTyph™ vaccine at 6 weeks interval. Control group received vaccines as per national guidelines. Adverse events (AEs) were examined after 30 minutes, 1 month and clinical events were observed till 12 months post-vaccination. Incidence of culture positive typhoid fever in the control group was 1.27% vis-a-vis none in vaccine group during 12 months. In subgroup evaluated for immunogenicity, an antibody titer value of 1.8 EU/ml (95% CI: 1.5 EU/ml, 2.2 EU/ml), 32 EU/ml (95% CI: 27.0 EU/ml, 39.0 EU/ml) and 14 EU/ml (95% CI: 12.0 EU/ml, 17.0 EU/ml) at baseline, 6 weeks and 12 months, respectively was observed. Sero-conversion among the sub-group was 100% after 6 weeks of post-vaccination and 83% after 12 months considering 4-fold rise from baseline. The efficacy of vaccine was 100 % (95% CI: 97.6%, 100%) in the first year of follow-up with minimal AEs post vaccination. Vi conjugate typhoid vaccine conferred 100% protection against typhoid fever in 1765 children 6 months to 12 years of age with high immunogenicity in a subgroup from the vaccine arm.

Immunogenicity and safety assessment of a trivalent, inactivated split influenza vaccine in Korean children: Double-blind, randomized, active-controlled multicenter phase III clinical trial.

A multicenter, double-blind, randomized, active-control phase III clinical trial was performed to assess the immunogenicity and safety of a trivalent, inactivated split influenza vaccine. Korean children between the ages of 6 months and 18 y were enrolled and randomized into a study (study vaccine) or a control vaccine group (commercially available trivalent, inactivated split influenza vaccine) in a 5:1 ratio. Antibody responses were determined using hemagglutination inhibition assay, and post-vaccination immunogenicity was assessed based on seroconversion and seroprotection rates. For safety assessment, solicited local and systemic adverse events up to 28 d after vaccination and unsolicited adverse events up to 6 months after vaccination were evaluated. Immunogenicity was assessed in 337 and 68 children of the study and control groups. In the study vaccine group, seroconversion rates against influenza A/H1N1, A/H3N2, and B strains were 62.0% (95% CI: 56.8-67.2), 53.4% (95% CI: 48.1-58.7), and 54.9% (95% CI: 48.1-60.2), respectively. The corresponding seroprotection rates were 95.0% (95% CI: 92.6-97.3), 93.8% (95% CI: 91.2-96.4), and 95.3% (95% CI: 93.0-97.5). The lower 95% CI limits of the seroconversion and seroprotection rates were over 40% and 70%, respectively, against all strains. Seroconversion and seroprotection rates were not significantly different between the study and control vaccine groups. Furthermore, the frequencies of adverse events were not significantly different between the 2 vaccine groups, and no serious vaccination-related adverse events were noted. In conclusion, the study vaccine exhibited substantial immunogenicity and safety in Korean children and is expected to be clinically effective.

Immunological persistence of a seasonal influenza vaccine in people more than 3 years old.

To evaluate antibody persistence of Aleph inactivated split influenza vaccine, 3308 healthy Chinese people more than 3 years old were enrolled in a hemagglutination inhibition (HI) assay before vaccination, 641 were screened by HI assay negative, 437 of which received one dose of Aleph inactivated split influenza vaccine and 204 of which received one dose of control vaccine (recombinant hepatitis B). After vaccination, the receivers were collected blood at 1st month, 3rd month, 6th month and 12th month for Aleh influenza vaccine antibody persistence assess. The antibody test were determined by hemagglutination inhibition (HI) assay. There were significant difference in antibody geometric mean titer between experimental group and control at 1st month and 3rd month after vaccination. Influenza antibody could persist at least up to 3rd month. Because of the local spring influenza epidemic, we could not analyze the results of 6th and 12th month. Aleph influenza vaccines showed good immune persistence in healthy volunteers at least in the 3 months after vaccination. Influenza viruses are important human respiratory pathogens. Immunization is widely acknowledged to currently be the most effective method of minimizing the impact of pandemic influenza. Through we have checked many references about Influenza vaccine, the duration of protective antibody for influenza vaccines are still not available. Based on this situation and our previous work, (11) Influenza vaccine antibody duration analyze are necessary. This manuscript presents data on the persistence of Hemagglutination Inhibition (HI) immune response against the A/California/7/2009(H1N1), A/Peth/16/2009(H3N2) strain and B/Brisbane/60/2008. 641 were screened from 3302 volunteers by HI test of influenza A and confirmed enrollment based on the antibodies titer less than 1:10. After administered with one dose of Aleph influenza vaccine, blood samples were collected. 437 subjects (3-10 y: 131; 11-17 y: 110; 18-54 y: 69; ≥ 55 y: 127) were vaccinated influenza vaccine as test group. 204 subjects (3-10 y: 70; 11-17 y: 47; 18-54 y: 28; ≥ 55 y: 59) were vaccinated recombinant hepatitis B vaccine as control group. Immunogenicity end points were based on the European licensure criteria for pandemic influenza vaccines. The persistence of HI immune response against the vaccine strain was assessed through GMT. The immunogenicity of the Aleph influenza vaccine induced all reached the standards at 1st month and GMTs peak could persist at least up to 3rd month. (This study has been registered at clinicaltrials.gov under registration no. NCT01758185.). Because of the local spring influenza epidemic we could not analyze the results of 6th and 12th month. Aleph influenza vaccines showed good immune persistence in healthy volunteers at least in the 3 months after vaccination.

Persistence of immunity in healthy adults aged ≥ 50 years primed with a hepatitis B vaccine 3 years previously.

Hepatitis B vaccines do not generate protective immune responses in older adults as effectively as they do in children and young adults. Improved formulations of existing vaccines may have the potential to improve this. This study investigated the persistence of serum antibodies against hepatitis B surface antigens (anti-HBs) 3.1-3.5 years following primary vaccination with 3 doses of HBvaxPRO® or Engerix B™ in healthy adults aged ≥ 50 years who were further challenged with 1 dose of recombinant hepatitis B antigen. This was an open-label extension study. Individuals (N = 204) with a mean (standard deviation) age at enrollment of 63.7 (7.0) years receiving HBvaxPRO® or Engerix B™ in a randomized, double-blind primary study were challenged with 1 dose of HBvaxPRO® (10 µg). Anti-HBs were measured pre- and 30 days post-challenge. 45.5% (34.8, 56.4 [95% CI]) of individuals who received HBvaxPRO® in the per protocol set (PPS) had anti-HBs titers ≥ 10 mIU/mL pre-challenge and 85.2% (76.1, 91.9) 1-month post-challenge. In those who received Engerix B™ in the primary vaccination series, the results were 58.8% (48.6, 68.5) and 88.3% (80.5, 93.8), respectively. The challenge dose of HBvaxPRO® was generally well tolerated. Subjects aged ≥ 50 years receiving a challenge dose of HBvaxPRO® demonstrated immune memory against hepatitis B 3 years after a 3-dose primary. The safety profile of this challenge dose of HBvaxPRO® was consistent with the well-established safety profile of the vaccine HBvaxPRO®.

Safety and immunogenicity of single dose live attenuated varicella vaccine (VR 795 Oka strain) in healthy Indian children: a randomized controlled study.

Varicella, an acute viral systemic infection that may cause lifelong latent infection with the potential for causing clinical reactivation, may be prevented by immunization. The present study was an open label, randomized, controlled, phase III, multicentre trial, conducted to evaluate and compare the safety, tolerability and immunogenicity of a freeze dried live attenuated Oka strain Varicella Vaccine (VR 795 Oka strain) with Varilrix (Oka-RIT strain) in children. A total of 268 healthy Indian children aged 12 months to 12 y with baseline VZV IgG antibody (<100 mIU/ mL) were enrolled, and 256 children completed the study. The extent of rise of VZV IgG antibody titer assessed as 3-fold and 4-fold rise from baseline was found to be significantly higher (89.1% and 85.2%) in the test group as compared to control group (73.4% and 61.7%). The post-vaccination GMT of the test group was significantly higher (112.5 mIU/mL) as compared with the control group (67.8 mIU/mL) (P < 0.001). The seroconversion rate considering the 5 gp ELISA units/ml equivalent to 10mIU/ml were similar in the control (96.5%) and the test (98.3%) groups. The adverse events were not different in the control and test groups (P > 0.05). The test live attenuated vaccine was found to be highly immunogenic, safe and comparable to Varilrix used in control arm.

Immunogenicity of intramuscular MF59-adjuvanted and intradermal administered influenza enhanced vaccines in subjects aged over 60: A literature review.

Because of the age-related immune system decline, 2 potentiated influenza vaccines were specifically licensed for the elderly: Fluad(®), an MF59-adjuvanted vaccine administered intramuscularly (IM-MF59), and Intanza 15 mcg(®), a non adjuvanted vaccine administered intradermally (ID). The objective of this paper was to conduct a systematic review of studies that evaluated antibody responses in the elderly following immunization with IM-MF59 or ID vaccines. The two potentiated vaccines induced immune responses satisfying, in most instances, the European Medicine Agency immunogenicity criteria, both against vaccine antigens and heterovariant drifted strains. Considering pooled data reported in the articles analyzed and papers directly comparing the 2 vaccines, the antibody responses elicited by IM-MF59 and ID were found to be generally comparable. The use of IM-MF59 and ID vaccines can be proposed as an appropriate strategy for elderly seasonal influenza vaccination although further studies are required for a more complete characterization of the 2 vaccines.

Immunogenicity and safety of investigational vaccine formulations against meningococcal serogroups A, B, C, W, and Y in healthy adolescents.

This phase 2 study assessed the immunogenicity, safety, and reactogenicity of investigational formulations of meningococcal ABCWY vaccines, consisting of recombinant proteins (rMenB) and outer membrane vesicle (OMV) components of a licensed serogroup B vaccine, combined with components of a licensed quadrivalent meningococcal glycoconjugate vaccine (MenACWY-CRM). A total of 495 healthy adolescents were randomized to 6 groups to receive 2 doses (Months 0, 2) of one of 4 formulations of rMenB antigens, with or without OMV, combined with MenACWY-CRM, or 2 doses of rMenB alone or one dose of MenACWY-CRM then a placebo. Immunogenicity was assessed by serum bactericidal assay with human complement (hSBA) against serogroups ACWY and serogroup B test strains; solicited reactions and any adverse events (AEs) were assessed. Two MenABCWY vaccinations elicited robust ACWY immune responses, with higher seroresponse rates than one dose of MenACWY-CRM. Bactericidal antibody responses against the rMenB antigens and OMV components were highest in subjects who received 2 doses of OMV-containing MenABCWY formulations, with ≥68% of subjects achieving hSBA titers ≥5 against each of the serogroup B test strains. After the first dose, solicited local reaction rates were higher in the MenABCWY or rMenB groups than the MenACWY-CRM group, but similar across groups after the second dose, consisting mainly of transient injection site pain. Fever (≥38.0°C) was rare and there were no vaccine-related serious AEs. In conclusion, investigational MenABCWY formulations containing OMV components elicited highly immunogenic responses against meningococcal serogroups ACWY, as well as serogroup B test strains, with an acceptable safety profile. [NCT01210885].

Immunogenicity and safety of cell-derived MF59®-adjuvanted A/H1N1 influenza vaccine for children.

Mass immunization of children has the potential to decrease infection rates and prevent the transmission of influenza. We evaluated the immunogenicity, safety, and tolerability of different formulations of cell-derived MF59-adjuvanted and nonadjuvanted A/H1N1 influenza vaccine in children and adolescents. This was a randomized, single-blind, multicenter study with a total of 666 healthy subjects aged 6 months-17 y in one of 3 vaccination groups, each receiving formulations containing different amounts of influenza A/H1N1 antigen with or without MF59. A booster trivalent seasonal MF59 vaccine was administered one year after primary vaccinations. Antibody titers were assessed by hemagglutination inhibition (HI) and microneutralization assays obtained on days 1, 22, 43, 366, and 387 (3 weeks post booster). Safety was monitored throughout the study. One vaccination with 3.75 µg of A/H1N1 antigen formulated with 50% MF59 (3.75_halfMF59) or 7.5 µg of A/H1N1 antigen formulated with 100% MF59 (7.5_fullMF59) induced an HI titer ≥1:40 in >70% of children in the 1-<3, 3-8, and 9-17 y cohorts; however, 2 vaccinations with nonadjuvanted 15 µg A/H1N1 antigen were needed to achieve this response in the 1-<3 and 3-8 y cohorts. Among children aged 6-11 months, 1 dose of 7.5_fullMF59 resulted in an HI titer ≥1:40 in >70% while 2 doses of 3.75_halfMF59 were required to achieve this result. All vaccines were well tolerated. Our findings support the immunogenicity and safety of the 3.75_halfMF59 (2 doses for children <12 months) and 7.5_fullMF59 vaccine formulations for use in children and adolescents aged 6 months to 17 y The use of the 3.75_halfMF59 could have the benefit of antigen and adjuvant sparing, increasing the available vaccine doses allowing vaccination of more people.

Intradermal vaccination using the novel microneedle device MicronJet600: Past, present, and future.

Intradermal immunization has become a forefront of vaccine improvement, both scientifically and commercially. Newer technologies are being developed to address the need to reduce the dose required for vaccination and to improve the reliability and ease of injection, which have been major hurdles in expanding the number of approved vaccines using this route of administration. In this review, 7 y of clinical experience with a novel intradermal delivery device, the MicronJet600, which is a registered hollow microneedle that simplifies the delivery of liquid vaccines, are summarized. This device has demonstrated both significant dose-sparing and superior immunogenicity in various vaccine categories, as well as in diverse subject populations and age groups. These studies have shown that intradermal delivery using this device is safe, effective, and preferred by the subjects. Comparison with other intradermal devices and potential new applications for intradermal delivery that could be pursued in the future are also discussed.