Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) in adults 56 years of age and older: a Phase II randomized study

MenACYW-TT is an investigational quadrivalent meningococcal conjugate vaccine intended for the prevention of invasive meningococcal disease (IMD) caused by serogroups A, C, W, and Y in individuals aged 6 weeks and above. This Phase II, randomized, open-label, multicenter, exploratory study assessed the safety and immunogenicity of MenACYW-TT compared with a quadrivalent meningococcal polysaccharide vaccine (MPSV4) in 301 healthy adults aged ≥56 y in the US (NCT01732627). Participants were randomized 2:1 to receive MenACYW-TT or MPSV4. Serum bactericidal assays using human (hSBA) or baby rabbit (rSBA) complement were used to measure functional antibodies against meningococcal serogroups A, C, W, and Y at baseline and 30 d post-vaccination. Safety data were collected up to 30 d post-vaccination. Proportions of study participants with hSBA titers ≥1:8 against serogroups A, C, W, and Y were increased at Day 30 compared with baseline in both vaccine groups. The proportions of participants with hSBA titers ≥1:8 after MenACYW-TT vaccination were comparable to those after MPSV4 vaccination for serogroups A and C (A: 93.8% vs. 85.1%; C: 74.9% vs. 62.8%) and distinctly higher than after MPSV4 for serogroups W and Y (W: 79.5% vs. 60.6%; Y: 80.5% vs. 59.6%). Proportions of participants with rSBA titers ≥1:8 were comparable between vaccine groups for all four serogroups. The reactogenicity profiles of both vaccines were similar. Most unsolicited adverse events (AEs) were of Grade 1 or Grade 2 intensity, and no serious AEs were reported. The MenACYW-TT conjugate vaccine was well tolerated and immunogenic in adults aged ≥56 y

03. Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) Administered as a Booster Dose in Adults and Adolescents Vaccinated Against Meningococcal Disease 3 - 6 Years Earlier

BACKGROUND: Booster doses of meningococcal conjugate vaccines may induce long-term protection against invasive meningococcal disease. MenACYW-TT [MenQuadfi®] is a quadrivalent meningococcal conjugate vaccine, licensed for use in ages 2 years and older in USA. The vaccine is also licensed in ages 12 months and older in EU and other countries. METHODS: A phase IIIb study (NCT04084769) was conducted to evaluate the persistence of immune response in adults and adolescents primed 3-6 years earlier with either MenACYW-TT or MCV4-CRM (Menveo®) and, safety and immunogenicity of MenACYW-TT when administered as a booster dose with or without concomitant administration with MenB vaccines (Bexsero® and Trumenba®). Serum bactericidal assays with human complement (hSBA) and baby rabbit complement (rSBA) were used to measure antibodies against vaccine serogroups at baseline (Day 0 [D0]), D06 (in a subset) and 30 days post-vaccination (D30). Safety data were collected up to 6 months post-vaccination. RESULTS: At D0, the GMTs were higher in subjects primed with MenACYW-TT vs MCV4-CRM for serogroups C, Y and W, and were comparable for serogroup A. At D0, all hSBA GMTs were higher than those observed pre-priming dose, suggesting persistence of immunity. Sufficiency of hSBA seroresponse ( >75%) was demonstrated following administration of MenACYW-TT booster dose regardless of the priming vaccine administered 3-6 years earlier. Vaccine seroresponse in a subset of participants at D06 ranged from 77.8% (95%CI 62.9%; 88.8%) for serogroup A to 97.8% (88.5%; 99.9%) for serogroup W suggesting a quick onset of immune response post-booster. Post-vaccination (D30) hSBA GMTs were comparable for serogroups A, Y and W regardless of the nature of the priming vaccine and were higher for serogroup C in subjects primed with MenACYW-TT vaccine. The MenACYW-TT booster dose was well-tolerated and had similar safety profiles regardless of the priming vaccine. The safety profiles were comparable regardless of the MenB vaccine co-administered with MenACYW-TT vaccine. CONCLUSION: MenACYW-TT used as priming vaccine was able to demonstrate persistence of immune response 3-6 years later. MenACYW-TT elicits robust booster responses in adults and adolescents primed with MenACYW-TT or MCV4-CRM DISCLOSURES: Betzana Zambrano, MD, Sanofi Pasteur (Employee) Germán Áñez, MD, Sanofi Pasteur (Other Financial or Material Support, Former employee) Sue Jiayuan, MSc, Sanofi Pasteur (Independent Contractor) Judy Pan, PhD, Sanofi Pasteur (Employee) Habiba Arroum, MD, Sanofi Pasteur (Employee) Kucku Varghese, PhD, Sanofi Pasteur (Employee) Emilia Jordanov, MD, Sanofi Pasteur (Employee, Shareholder) Mandeep S. Dhingra, MD, Sanofi Pasteur (Employee, Shareholder

Immunogenicity and safety of an investigational quadrivalent meningococcal conjugate vaccine administered as a booster dose in children vaccinated against meningococcal disease 3 years earlier as toddlers : A Phase III, open-label, multi-center study

Booster doses of meningococcal conjugate vaccines induce long-term protection against invasive meningococcal disease. We evaluated the immunogenicity and safety of a booster dose of MenACYW-TT in pre-school children who were primed 3 years earlier with MenACYW-TT or MCV4-TT (Nimenrix®). In this Phase III, open-label, multi-center study (NCT03476135), children (4–5 years old), who received a primary dose of MenACYW-TT or MCV4-TT as toddlers in a previous study, received a booster dose of MenACYW-TT. Titers of antibody against meningococcal serogroups A, C, W and Y were measured by serum bactericidal assay using human (hSBA) and baby rabbit (rSBA) complement in samples collected before (D0) and 30 days after (D30) booster vaccination. Safety was assessed over the 30-day study period. Ninety-one participants received the booster dose. In both study groups, hSBA titers increased from D0 to D30; serogroup C titers [95% confidence interval] were higher in the MenACYW-TT-primed vs MCV4-TT-primed group at D0 (106 [73.2, 153] vs 11.7 [7.03, 19.4], respectively) and D30 (5894 [4325, 8031] vs 1592 [1165, 2174], respectively); rSBA results were similar. Nearly all participants achieved ≥1:8 hSBA and rSBA titers at D30, which were higher or comparable to those observed post-primary dose, suggesting rapid booster responses. At D0, all hSBA and rSBA titers were higher than those observed pre-primary dose, suggesting persistence of immunogenicity. The MenACYW-TT booster dose was well-tolerated and had similar safety outcomes across study groups. These findings suggest that MenACYW-TT elicits robust booster responses in children primed 3 years earlier with MenACYW-TT or MCV4-TT.publishedVersionPeer reviewe

Evaluation of the immunogenicity and safety of an indigenously developed DTwP-Hib tetravalent combination vaccine (Shan 4) with Easyfour™ in Indian infants administered per EPI schedule: A phase III trial

The study was planned to assess and compare immunogenicity and safety of an indigenous DTPw-Hib combination vaccine (Shan 4) with EasyFour, the available DTwP-Hib vaccine in India. Overall 210 healthy infants, six to eight weeks of age, were randomized to receive three doses of either Shan 4 or EasyFour at 6, 10 and 14 weeks of age. Antibodies were analyzed prior to and four to six weeks post third vaccine dose. Solicited and unsolicited local and systemic events in the follow up period after each dose were recorded. Post vaccination 100% of the infants in Shan 4 and EasyFour groups had seroprotective concentrations of Anti PRP-T IgG antibodies, IgG anti-diphtheria toxoid antibodies and IgG anti-tetanus toxoid antibodies. Following third dose of vaccination 86.99% subjects in the Shan 4 group and 73.85% subjects in the EasyFour group seroconverted for anti-pertussis antibody titres. Two Serious Adverse Events (SAEs) were reported during the course of the study, all unrelated to the respective vaccine administered. Most commonly reported adverse events in both the groups were pain at injection site, mild fever (<103°F) and minor swelling at injection site. The study proved that Shan 4 was safe and immunogenic compared to the available licensed vaccine

Vibriocidal antibody responses to a bivalent killed whole-cell oral cholera vaccine in a phase III trial in Kolkata, India.

During the development of a vaccine, identification of the correlates of protection is of paramount importance for establishing an objective criterion for the protective performance of the vaccine. However, the ascertainment of correlates of immunity conferred by any vaccine is a difficult task.While conducting a phase three double-blind, cluster-randomized, placebo-controlled trial of a bivalent killed whole-cell oral cholera vaccine in Kolkata, we evaluated the immunogenicity of the vaccine in a subset of participants. Randomly chosen participants (recipients of vaccine or placebo) were invited to provide blood samples at baseline, 14 days after the second dose and one year after the first dose. At these time points, serum geometric mean titers (GMT) of vibriocidal antibodies and seroconversion rates for vaccine and placebo arms were calculated and compared across the age strata (1 to 5 years, 5 to 15 years and more than 15 years) as well as for all age groups.Out of 137 subjects included in analysis, 69 were vaccinees and 68 received placebo. There were 5•7 and 5•8 geometric mean fold (GMF) rises in titers to Vibrio cholerae Inaba and Ogawa, respectively at 14 days after the second dose, with 57% and 61% of vaccinees showing a four-fold or greater titer rise, respectively. After one year, the titers to Inaba and Ogawa remained 1•7 and 2•8 fold higher, respectively, compared to baseline. Serum vibriocidal antibody response to V. cholerae O139 was much lower than that to Inaba or Ogawa. No significant differences in the GMF-rises were observed among the age groups.The reformulated oral cholera vaccine induced a statistically significant anti-O1 Inaba and O1 Ogawa vibriocidal antibody response 14 days after vaccination, which although declined after one year remained significantly higher than baseline. Despite this decline, the vaccine remained protective five years after vaccination

Association of rotavirus strains and severity of gastroenteritis in Indian children

Rotavirus is the leading cause of severe and dehydrating diarrhea in children aged under 5 years. We undertook this hospital-based surveillance study to examine the possible relationship between the severity of diarrhea and the various G-group rotaviruses circulating in India. Stool samples (n = 2,051) were systematically collected from 4,711 children aged <5 years admitted with severe acute gastroenteritis to 12 medical school centers from April 2011 to July 2012. Rotavirus testing was undertaken using a commercially available enzyme immunoassay kit for the rotavirus VP6 antigen (Premier Rotaclone Qualitative ELISA). Rotavirus positive samples were genotyped for VP7 and VP4 antigens by reverse-transcription polymerase chain reaction at a central laboratory. Of the stool samples tested for rotavirus antigen, 541 (26.4%) were positive for VP6 antigen. Single serotype infections from 377 stool samples were compared in terms of gastroenteritis severity. Among those with G1 rotavirus infection, very severe diarrhea (Vesikari score ≥ 16) was reported in 59 (33.9%) children, severe diarrhea (Vesikari score 11–15) in 104 (59.8%), moderate (Vesikari score 6–10) and mild diarrhea (Vesikari score 0–5) in 11 (6.3%). Among those with G2 infection, very severe diarrhea was reported in 26 (27.4%) children, severe diarrhea in 46 (48.4%), and moderate and mild diarrhea in 23 (24.2 %). Among those with G9 infection, very severe diarrhea was reported in 47 (54.5%) children, severe diarrhea in 29 (33.6%), and moderate and mild diarrhea in 10 (11.9%). Among those with G12 infection, very severe diarrhea was reported in 9 (40.9%) children and severe diarrhea in 13 (59.1%). The results of this study indicate some association between rotavirus serotypes and severity of gastroenteritis

Hexachlorocyclohexane-degrading bacterial strains Sphingomonas paucimobilis B90A, UT26 and Sp+, having similar lin genes, represent three distinct species, Sphingobium indicum sp. nov., Sphingobium japonicum sp. nov. and Sphingobium francense sp. nov., and reclassification of [Sphingomonas] chungbukensis as Sphingobium chungbukense comb. nov.

Three strains of Sphingomonas paucimobilis, B90A, UT26 and Sp+, isolated from different geographical locations, were found to degrade hexachlorocyclohexane. Phylogenetic analysis based on 16S rRNA gene sequences indicated that these strains do not fall in a clade that includes the type strain, Sphingomonas paucimobilis ATCC 29837T, but form a coherent cluster with [Sphingomonas] chungbukensis IMSNU 11152T followed by Sphingobium chlorophenolicum ATCC 33790T. The three strains showed low DNA–DNA relatedness values with Sphingomonas paucimobilis ATCC 29837T (8–25 %), [Sphingomonas] chungbukensis IMSNU 11152T (10–17 %), Sphingobium chlorophenolicum ATCC 33790T (23–54 %) and Sphingomonas xenophaga DSM 6383T (10–28 %), indicating that they do not belong to any of these species. Although the three strains were found to be closely related to each other based on 16S rRNA gene sequence similarity (99·1–99·4 %), DNA–DNA relatedness (19–59 %) and pulsed-field gel electrophoresis (PFGE) patterns indicated that they possibly represent three novel species of the genus Sphingobium. The three strains could also be readily distinguished by biochemical tests. The three strains showed similar polar lipid profiles and contained sphingoglycolipids. The strains differed from each other in fatty acid composition but contained the predominant fatty acids characteristic of other Sphingobium species. A phylogenetic study based on 16S rRNA gene sequences showed that [Sphingomonas] chungbukensis IMSNU 11152T formed a cluster with members of the genus Sphingobium. Based on these results, it is proposed that strains B90A, UT26 and Sp+, previously known as Sphingomonas paucimobilis, are the type strains of Sphingobium indicum sp. nov. (=MTCC 6364T=CCM 7286T), Sphingobium japonicum sp. nov. (=MTCC 6362T=CCM 7287T) and Sphingobium francense sp. nov. (=MTCC 6363T=CCM 7288T), respectively. It is also proposed that [Sphingomonas] chungbukensis be transferred to Sphingobium chungbukense comb. nov

Comparison of geometric mean fold rises across age groups among vaccine recipients in Kolkata, India.

<p>*Age at the date of 1^st dose.</p>†<p>GMT refers to Geometric mean titers.</p>‡<p>GMF refers to Geometric Mean Fold.</p>§<p>The p-value is either nominal from one way ANOVA or simulated using somanova implemented in STATA depending on the results of the Bartlett’s test for equal variance (described in the text).</p

CONOSRT for assembling the subjects.

<p>CONOSRT for assembling the subjects.</p