Serum-free purified Vero rabies vaccine is safe and immunogenic in children: Results of a randomized phaseII pre-exposure prophylaxis regimen study.

BACKGROUND: A serum-free, highly purified Vero rabies vaccine (PVRV-NG) has been developed with no animal or human components and low residual DNA content. A phaseII randomized clinical study aimed to demonstrate the non-inferiority of the immune response and assess the safety profile of PVRV-NG versus a licensed human diploid cell culture rabies vaccine (HDCV) in a pre-exposure regimen in healthy children and adolescents in the Philippines. METHODOLOGY: Children aged 2-11 years and adolescents aged 12-17 years were randomized (2:1) to receive three injections of either PVRV-NG or HDCV (on day [D] 0, D7 and D28). Rabies virus-neutralizing antibodies (RVNA) were measured at D0, D42 and 6 months after the first injection (month [M] 6). Safety was assessed during the vaccination period and up to 28 days after the last vaccination. Serious adverse events were followed until 6 months after last vaccination. PRINCIPAL FINDINGS: 342 healthy participants (171 children and 171 adolescents) were randomized and followed for 6 months after the last dose. All participants in both groups had an RVNA titer ≥ 0.5 IU/ml at D42, demonstrating non-inferiority in seroconversion rate for PVRV-NG versus HDCV. Over 90% of participants had RVNA titer ≥ 0.5 IU/ml at M6. PVRV-NG was well tolerated after each vaccination and up to 6 months following the last dose. There were no major safety concerns during the study, and the type and severity of solicited adverse events was similar for both treatment groups. CONCLUSIONS: This study demonstrated the non-inferior immune profile of PVRV-NG compared with HDCV in a pre-exposure setting within a pediatric population. PVRV-NG was well tolerated with no safety concerns. This study is registered at ClinicalTrials.gov (NCT01930357) and EU Clinical Trials Register (2015-003203-30).

Immunogenicity and safety of the 2015 Southern Hemisphere formulation of a split-virion inactivated quadrivalent vaccine.

An inactivated split-virion quadrivalent influenza vaccine (IIV4; Fluzone® Quadrivalent; Sanofi Pasteur) has been available in the US since 2013 and in the Southern Hemisphere since 2015. Here, we describe the results of an open-label, post-licensure trial (WHO Universal Trial Number, U1111-1143-9256) to confirm the immunogenicity and safety of the Southern Hemisphere 2015 formulation of IIV4. Adults 18-60 years of age and > 60 years of age (n = 60 per age group) received a single 0.5-mL intramuscular injection of IIV4. After vaccination, hemagglutination inhibition titers for each strain in IIV4 increased by a geometric mean of at least 10-fold for younger adults and at least 9-fold for older adults. All of the younger adult participants and 98%-100% of the older adult participants had seroprotective titers for each strain. Also, at least 80% of younger adults and 78% of older adults seroconverted or had a significant increase in titer for all four vaccine strains. These post-vaccination immune responses exceeded the criteria of the Committee for Human Medicinal Products former Note for Guidance for influenza vaccines. Finally, no serious adverse events were reported, and no new safety signals were detected. These results confirmed that the Southern Hemisphere 2015 formulation of IIV4 was well tolerated, highly immunogenic, and met the criteria for influenza vaccine immunogenicity and safety.

Long-term immunogenicity and safety after a single dose of the quadrivalent meningococcal serogroups A, C, W, and Y tetanus toxoid conjugate vaccine in adolescents and adults: 5-year follow-up of an open, randomized trial.

BACKGROUND: Long-term protection against meningococcal disease is associated with persistence of post-vaccination antibodies at protective levels. We evaluated the bactericidal antibody persistence and safety of the quadrivalent meningococcal serogroups A, C, W and Y tetanus-toxoid conjugate vaccine (MenACWY-TT) and the meningococcal polysaccharide serogroups A, C, W, and Y vaccine (MenACWY-PS) up to 5 years post-vaccination. METHODS: This phase IIb, open, randomized, controlled study conducted in the Philippines and Saudi Arabia consisted of a vaccination phase and a long-term persistence phase. Healthy adolescents and adults aged 11-55 years were randomized (3:1) to receive a single dose of MenACWY-TT (ACWY-TT group) or MenACWY-PS (Men-PS group). Primary and persistence results up to 3 years post-vaccination have been previously reported. Antibody responses against meningococcal serogroups A, C, W, and Y were assessed by a serum bactericidal antibody assay using rabbit complement (rSBA, cut-off titers 1:8 and 1:128) at Year 4 and Year 5 post-vaccination. Vaccine-related serious adverse events (SAEs) and cases of meningococcal disease were assessed up to Year 5. RESULTS: Of the 500 vaccinated participants, 404 returned for the Year 5 study visit (Total Cohort Year 5). For the Total Cohort Year 5, 71.6-90.0 and 64.9-86.3 % of MenACWY-TT recipients had rSBA titers ≥1:8 and ≥1:128, respectively, compared to 24.8-74.3 and 21.0-68.6 % of MenACWY-PS recipients. The rSBA geometric mean titers (GMTs) remained above the pre-vaccination levels in both treatment groups. Exploratory analyses suggested that both rSBA GMTs as well as the percentages of participants with rSBA titers above the cut-offs were higher in the ACWY-TT than in the Men-PS group for serogroups A, W and Y, with no apparent difference for MenC. No SAEs related to vaccination or cases of meningococcal disease were reported up to Year 5. CONCLUSION: These results suggest that a single dose of MenACWY-TT could protect at least 72 % of vaccinated adolescents and adults against meningococcal disease at least 5 years post-vaccination. TRIAL REGISTRATION: ClinicalTrials.gov NCT00356369.

Immune response, antibody persistence, and safety of a single dose of the quadrivalent meningococcal serogroups A, C, W-135, and Y tetanus toxoid conjugate vaccine in adolescents and adults: results of an open, randomised, controlled study.

BACKGROUND: The best strategy to protect individuals against meningococcal disease is to immunize against multiple serogroups. Immunogenicity, antibody persistence, and safety of the EU-licensed meningococcal ACWY-tetanus toxoid conjugate vaccine (MenACWY-TT) were evaluated in healthy participants aged 11-55 years from the Philippines and Saudi Arabia. METHODS: In this phase IIb, open, controlled study, 500 participants were randomised (3:1) to receive one dose of MenACWY-TT or a licensed meningococcal polysaccharide vaccine (Men-PS). Functional antibody responses against meningococcal serogroups A, C, W-135, and Y were assessed by a serum bactericidal antibody assay using rabbit complement (rSBA) at Month 0, Month 1, Year 1, Year 2, and Year 3. Vaccine response was defined as an rSBA titre ≥32 at Month 1 in participants who were seronegative (rSBA titre <8) pre-vaccination and as at least a four-fold increase in titre in participants who were seropositive pre-vaccination. Solicited symptoms were recorded up to Day 4, safety outcomes up to Month 6, and serious adverse events related to vaccination up to Year 3. RESULTS: Pre-specified criteria for non-inferiority of MenACWY-TT versus Men-PS were met in terms of rSBA vaccine response and incidence of grade 3 general symptoms. At Month 1, 82.7%-96.3% of MenACWY-TT and 69.7%-91.7% in Men-PS recipients had a vaccine response for each serogroup. At Year 3, ≥99.1% and ≥92.9% of MenACWY-TT recipients retained rSBA titres ≥8 and ≥128, respectively, as compared to ≥86.7% and ≥80.0% in the Men-PS group. Both vaccines had a clinically acceptable safety profile, although injection site redness and swelling were more frequent in MenACWY-TT recipients. CONCLUSIONS: These results suggest that MenACWY-TT could protect adolescents and adults against meningococcal disease up to three years post-vaccination. TRIAL REGISTRATION: This study is registered at http://www.clinicaltrials.gov/NCT00356369.

Rabies awareness in eight Asian countries.

Rabies is a deadly zoonotic disease most often transmitted to humans through a dog bite. Human mortality from endemic canine rabies is estimated by WHO to be around 55,000 deaths annually, with over 31,000 deaths in Asia alone, mostly children. Most of these deaths could be prevented through post-exposure prophylaxis (PEP), including immediate wound washing, rabies immunoglobulin administration and vaccination. Unfortunately, at-risk populations are not well-informed of the risk of rabies and what to do in the event of an animal bite. In order to identify the main gaps in rabies information and better define the most urgent information actions to be undertaken, the Asian Rabies Expert Bureau (AREB) conducted a multicentre, multi-country survey of patients seeking rabies post-exposure prophylaxis in rabies prevention centres from 1 July 2007 to 31 January 2008, in Bangladesh, China, India, Indonesia, Pakistan, the Philippines, Sri Lanka, and Thailand. Questionnaires were completed for 4377 subjects in the eight countries. Data was collected regarding the patient, former rabies exposures, the present wound, rabies exposure management, and rabies awareness. Two major issues were identified where active information of the population could make a difference: the necessity to apply appropriate wound care and to consult the nearest rabies prevention centre as soon as possible.