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Background Sci-B-Vac®, a 3-antigen hepatitis B vaccine (3A-HBV), contains all three recombinant hepatitis B virus (HBV) envelope proteins (S, pre-S1, and pre-S2). In 2005, 3A-HBV manufacturing transferred facilities (A to B), where it continues to be manufactured. Methods This phase 3, single-blind, randomized study, conducted at one site in Vietnam, compared efficacy and safety among two 3A-HBV lots, lot A and lot B, and a single-antigen hepatitis B vaccine (1A-HBV), Engerix-B®. Primary objective was to demonstrate equivalence at day 210 of two 3A-HBV lots in seroprotection rate (SPR; defined as percentage of participants achieving hepatitis B surface antigen antibody [anti-HBs] titers ≥ 10 mIU/mL). Secondary objectives were assessing immunogenicity at days 180, 210, and 360, and safety of 3A-HBV. Results 3A-HBV SPR equivalence was demonstrated at day 210 (lot A: 97.3% [95% CI: 92.4%, 99.4%] vs. lot B: 100.0% [97.0%, 100.0%]). Compared to 1A-HBV, lot B SPR was higher at day 180 (98.3% vs. 81.2%; difference: 17.1% [9.7%, 24.6%]) and non-inferior at day 210 (100% vs. 98.3%; difference: 1.7% [-0.6%, 4.1%]). 3A-HBV lot B showed the same SPR after 2 doses (98.3%) as 1A-HBV after 3 doses (98.3%). Adverse events (AEs) were comparable with both 3A-HBV lots (lot A: 68.7% vs. lot B: 54.2%), but higher than 1A-HBV (35.3%). Vaccination-related AEs included transient injection site pain (38.9%), myalgia (9.3%), and fatigue (7.5%). Eight serious AEs were reported (lot A: 3/134 [2.2%]; lot B: 1/134 [0.8%]; 1A-HBV: 4/133 [2.3%]). One serious AE, syncope, was noted as probably related to study vaccine, lot B. Conclusions The two 3A-HBV lots had equivalent immunogenicity, but lot B elicited faster onset of seroprotection and higher anti-HBs titers than both lot A and 1A-HBV in an Asian population. This supports 3A-HBV lot B as an effective choice for HBV vaccination, with a favorable safety profile. ClinicalTrials.gov: NCT04531098.

Background The currently licensed aluminum-hydroxide-adjuvanted hepatitis B vaccines require three doses over a 6-month period to achieve high rates of protection in adults. We compared tolerability and immunogenicity of two doses of an investigational hepatitis B vaccine using hepatitis B surface antigen adjuvanted with an immunostimulatory phosphorothioate oligodeoxyribonucleotide (HBV-ISS) to three doses of a licensed alum-adjuvanted vaccine (HBV-Eng). Methods In this randomized, observer-blind study, healthy adults received two doses of HBV-ISS at 0 and 4 weeks or three doses of HBV-Eng at 0, 4, and 24 weeks. The primary immunogenicity endpoint was the seroprotection rate (antibody ≥ 10 mIU/mL) 8 weeks after the second dose of HBV-ISS compared to 4 weeks after the third dose of HBV-Eng. Results A total of 2415 participants were randomized in a ratio of 3:1 to HBV-ISS (n = 1809) and HBV-Eng (n = 606). The percentage of subjects exhibiting a seroprotective immune response at the primary time point was significantly higher (95.1%) for HBV-ISS than for HBV-Eng (81.1%). Superiority of the seroprotective rates for HBV-ISS was demonstrated at all time points measured. Geometric mean concentrations were also significantly higher in the HBV-ISS group at all time points measured except at week 28 (24 weeks post-second dose of HBV-ISS and 4 weeks post-third dose HBV-ISS) at which time the antibody concentrations were similar. Both vaccines were welltolerated although injection-site reactions were reported at a higher rate in HBV-ISS recipients. Conclusions A short, two-dose regimen of HBV-ISS induced a superior antibody response than a three-dose regimen of a licensed hepatitis B vaccine and was well tolerated.

Despite the extensive efforts towards development of an effective HIV vaccine, major challenges surrounding vaccine design still exist. We have previously developed a unique multivalent HIV-1 candidate vaccine representing hypervariable Gp120 and Gag regions. This candidate vaccine was able to induce a broad cell-mediated immune response in HLA-A2.1 mice and non-human primates against HIV-1 subtypes A–F. Herein, the reactivity of each hypervariable peptide mixture within our candidate peptide vaccine was further characterized to optimize the final vaccine formulation for the future clinical studies. The binding of each hypervariable region to sera from HIV-infected individuals demonstrated a strong reactivity between the antibodies and hypervariable regions. In addition, 15 groups of mice were immunized with adjuvant alone or each individual peptide mixture (lipidated or non-lipidated) to evaluate the ability of each variable region to induce humoral and cellular immune responses against HIV-1. A reactive HIV-1 specific immune response was detected among the immunized groups; however, mice receiving the Gag hypervariable regions demonstrated the highest frequency of cell-mediated immune responses.

Combination vaccines improve parental and provider satisfaction and schedule compliance by decreasing the number of injections. In a Phase 2, randomized, double-blind, multicenter study, we compared four formulations of a liquid, hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B virus (DTaP-IPV-Hib-HBV) vaccine in 708 infants immunized at 2, 3, 4, and 12-14 months of age. The formulations contained identical DTaP and IPV components, differing in the contents of Hib polyribosylribitol phosphate (PRP) conjugate component (tetanus-toxoid [PRP-T, 12microg] or Neisseria meningitidis outer-membrane-protein-complex [PRP-OMPC, 3microg or 6microg]), and in hepatitis B surface antigen (HBsAg, 10microg or 15microg). A minimum acceptable postdose 3 antibody response rate was defined by the lower limit of the 95% confidence interval exceeding a prespecified target. Rates of adverse events (AEs) were similar among groups, with a trend for increased solicited injection-site reactions (pain, redness, swelling) with increasing PRP-OMPC and HBsAg concentration. Serious AEs reported by eight subjects were not considered to be vaccine related. All PRP-OMPC formulations met prespecified acceptability criteria for postdose 3 immunogenicity for all antigens: PRP, HBsAg, pertussis, diphtheria, tetanus and polio. Apart from the Hib response, the postdose 3 responses obtained with the PRP-T formulation met the acceptability criterion for each antigen. Postdose 4 responses were acceptable for all antigens in all formulations. All vaccine formulations were well tolerated. The three PRP-OMPC formulations met prespecified immunogenicity criteria, and the one with the lowest PRP-OMPC concentration was selected for further optimization of immunogenicity.

Summary Two cohorts, comprising of subjects aged 1–6 years and 6–15 years were vaccinated with Twinrix ™ according to a 0-, 1- and 6-month schedule. The 1–6 years cohort was followed up for 7.5 years and the 6–15 years cohort for 10 years. At the latest follow-up time point, all subjects were seropositive for anti-HAV antibodies, while 86.5% (32/37) and 95.5% (21/22) had anti-HBs ≥ 10 mIU/ml in the 1–6 years and in the 6–15 years cohort. The geometric mean concentrations (GMCs; mIU/ml) were 233 and 680 for anti-HAV antibodies, and 147 and 165 for anti-HBs antibodies, in the 1–6 years and 6–15 years cohorts, respectively. The high persistence of circulating anti-HAV and anti-HBs antibodies in children and adolescents demonstrates the long-term protection offered by Twinrix ™ in these age groups.

Background Herpes zoster (HZ) incidence rises with age, especially after 50 years of age, probably due to waning varicella-zoster virus (VZV)-specific immunity. The Shingles Prevention Study [Oxman MN, Levin MJ, Johnson GR, Schmader KE, Straus SE, Gelb LD, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults, N Engl J Med 2005;352:2271–84], enrolled people ≥60 years of age and showed that zoster vaccine prevents HZ and postherpetic neuralgia (PHN), presumably through boosting VZV-specific immunity. This study of people ≥50 years of age compared the safety and tolerability of two zoster vaccine potencies. Methods Adults ≥50 years old enrolled in a randomized, double-blind, multicenter study to compare the safety and tolerability of one dose of two zoster vaccine potencies, ∼58,000 and ∼207,000 plaque-forming units/dose. Adverse experiences (AEs) were recorded on a standardized Vaccination Report Card for 42 days postvaccination. For assessment of injection-site AEs, clinically acceptable tolerability was predefined based on experience with PNEUMOVAX™ 23, a licensed vaccine recommended for use in older people. Results Six hundred and ninety-eight subjects (age 50–90 years, median 64 years) were enrolled. No serious vaccine-related AEs were reported. Similar AE rates were observed in the higher and lower potency groups (overall systemic AEs: 37.5 and 39.3%, vaccine-related systemic AEs: 10.9 and 13.2%, injection-site AEs: 63.0 and 59.8%). Rates for a combined endpoint of moderate or severe injection-site pain/tenderness/soreness and swelling were 17.2% (95% CI 13.9, 21.0) and 9.0% (95% CI 5.6, 13.4), respectively. Most combined endpoint events were reported as moderate in intensity. Conclusions Both vaccine potencies were generally well tolerated in this study of people ≥50 years of age. Although rates of some moderate or severe injection-site AEs were greater in the higher potency group, all rates met the prespecified criteria for clinically acceptable tolerability.

Millions of vaccine doses are wasted each year due to a lapse in recommended storage conditions. Maintaining the cold chain for vaccines is both expensive and difficult, especially in developing countries. The present study investigated the safety and immunogenicity of a single dose of the conjugated meningococcal Group C vaccine, Menjugate, stored for 6 months at room temperature (25+/-2 degrees C, N=250) or at 2-8 degrees C (N=250) when administered to 12-23 months toddlers. In the two respective groups, 87 and 88% of toddlers reached bactericidal antibodies titers of at least 1:8. The immunogenicity of Menjugate stored at room temperature was not inferior to that stored at 2-8 degrees C. The safety profile and immunogenicity of the vaccine was not influenced by the storage condition.

In Canada, the fifth dose of the routine childhood immunization schedule against diphtheria, tetanus, pertussis and polio is given at 4-6 years of age. Up to 30% of children may have significant local reactions (redness, swelling) and this may be related to pertussis and diphtheria antigen content. We sought to determine if a combination product with lower content of pertussis and diphtheria toxoids (dTap) would result in fewer local reactions and not have inferior immunogenicity to a combination vaccine with higher pertussis and diphtheria content (diphtheria-tetanus-acellular pertussis-inactivated polio virus, DTaP-IPV). Healthy children aged 4-6 years with complete primary immunization series and a fourth dose of diphtheria and tetanus toxoids component pertussis inactivated polio and Haemophilus influenzae type B conjugate vaccine were randomized to one dose of dTap, followed in 4-6 weeks by one dose of IPV or control DTaP-IPV. Immediate reactions within 30 min, solicited injection site and systemic reactions within 14 days, and unsolicited adverse events (AE) within 6 weeks post-vaccination were monitored. Serum was collected prior to immunization, and 4-6 weeks after vaccine for diphtheria, tetanus and pertussis antibodies (Ab). Sample size was designed to detect > or =10% difference in injection site erythema, pain or swelling between groups 593 children at eight Canadian sites completed the study; no participant withdrew because of an AE. All safety endpoints on days 0-14 were less frequent in children randomized to the dTap than DTaP-IPV group: erythema (34.6% versus 51.7%), swelling (24.2% versus 33.8%) and pain (39.6% versus 67.2%). Fever was also less common (8.72% versus 16.9%). All children in both study groups had seroprotective Ab levels to diphtheria and tetanus at 4-6 weeks (> or =0.10 IU/mL). The majority of children in each vaccine arm had a four-fold increase in pertussis antibodies. Fever and injection site reactions are less common in 4-6 year-old-children who receive a dTap vaccine compared to DTaP-IPV, without inferior immunogenicity.

The mucosal immune system appears to be a major target of the HIV infection. Therefore, a strong pre-existing anti-HIV immune response in mucosal compartments might be able to prevent HIV infection. Conflicting views regarding the mechanisms of protection at mucosal sites, inferred by the contradictory results of mucosal vaccines in human clinical trials, attests to our lack of knowledge in understanding the human mucosal immune system. In this article, we briefly review the function of innate and adaptive immune responses and discuss current strategies and potential adjuvants in designing and delivering HIV vaccines through mucosal routes.

Background Since 1998, all children in Canada have been immunized with a pentavalent diphtheria and tetanus toxoids, acellular pertussis, inactivated poliovirus, Haemophilus influenzae type b conjugate vaccine (DTaP-IPV-Hib) produced by one manufacturer (Pentacel™). Recently, another DTaP-IPV-Hib (Infanrix™-IPV-Hib) became available. Data on the interchangeability of these products was lacking. Methods In this multicentered, observer-blind study, healthy 15–20-month-old children previously immunized with three doses of Pentacel™ were randomly allocated to receive a single dose of Pentacel™ or Infanrix™-IPV-Hib. Adverse events were documented by diary for 7 days post-immunization and unsolicited adverse events were documented for 30 days. Results 433 participants were enrolled (mean age 17.1 months). Rates of fever, anorexia and irritability were similar in both groups. Injection-site redness >20 mm (11.5% versus 5.6%; p = 0.038), injection-site pain (52.1% versus 39.4%; p = 0.009) and moderate or greater drowsiness (13.8% versus 7.4%; p = 0.042) were more common after Pentacel™ than Infanrix™-IPV-Hib. The proportions of participants who were seroprotected or who seroresponded were similar for all antigens. Geometric mean titers or concentrations were similar for antibodies against diphtheria toxoid and poliovirus type 3. Geometric mean concentrations or titers were higher in the Infanrix™-IPV-Hib group against pertussis toxin (88.5 EU/mL versus 65.6 EU/mL), filamentous hemagglutinin (207.3 EU/mL versus 132.1 EU/mL), pertactin (251.9 EU/mL versus 166.9 EU/mL) and poliovirus type 1 (1293.7 versus 976.2 reciprocal dilution). Geometric mean titers or concentrations were higher in the Pentacel™ group against H. influenzae type b (29 μg/mL versus 19 μg/mL), tetanus toxoid (5.6 IU/mL versus 4.7 IU/mL) and poliovirus type 2 (1437.3 versus 1134.2 reciprocal dilution). Conclusions A booster dose of Infanrix™-IPV-Hib after three priming doses of Pentacel™ is well-tolerated and immunogenic in 15–20-month-old toddlers and can be used interchangeably.