Safety and immunogenicity of a multidose vial formulation of 13-valent pneumococcal conjugate vaccine administered with routine pediatric vaccines in healthy infants in India: A phase 4, randomized, open-label study.

PURPOSE: This phase 4, randomized, open-label, multicenter study in healthy Indian infants and toddlers evaluated the safety, tolerability, and immunogenicity of the 13-valent pneumococcal conjugate vaccine (PCV13) formulated in a multidose vial (MDV) or single prefilled syringe (PFS). METHODS: Healthy Indian infants (6 weeks of age) were randomized 1:1 to receive either PCV13-MDV or PCV13-PFS concomitant with routine pediatric vaccines. Subjects received a single dose of either PCV13-MDV or PCV13-PFS as a 4-dose schedule (infant series: 1 dose at 6, 10, and 14 weeks of age; toddler dose: 12 months of age). Safety was assessed, including local reactions, systemic events, and adverse events (AEs). Immunogenicity 1 month after both the infant series and toddler dose was measured by concentrations of serotype-specific immunoglobulin G (IgG) antibodies and opsonophagocytic activity titers. RESULTS: Rates and severities of local reactions and systemic events up to 7 days after each dose of either PCV13-MDV or PCV13-PFS were generally similar, with the majority being of mild or moderate severity. PCV13-MDV had a safety profile comparable with PCV13-PFS; both groups experienced a similar frequency of AEs. PCV13-MDV elicited immune responses comparable with those induced by PCV13-PFS. Clear boosting of immune responses after the PCV13-MDV toddler dose was observed; ≥96% of subjects showed serotype-specific IgG concentrations at or above the defined thresholds 1 month after the PCV13-MDV toddler dose. CONCLUSIONS: PCV13-MDV was safe, well tolerated, and immunogenic in healthy Indian infants and toddlers when coadministered with routine pediatric vaccinations. Safety and immunogenicity of PCV13-MDV was comparable with PCV13-PFS. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov: NCT03548337.

A phase III randomized, open-label, non-inferiority clinical trial comparing liquid and lyophilized formulations of oral live attenuated human rotavirus vaccine (HRV) in Indian infants.

The human rotavirus vaccine (HRV; Rotarix, GSK) is available as liquid (Liq) and lyophilized (Lyo) formulations, but only Lyo HRV is licensed in India. In this phase III, randomized, open-label trial (NCT02141204), healthy Indian infants aged 6-10 weeks received 2 doses (1 month apart) of either Liq HRV or Lyo HRV. Non-inferiority of Liq HRV compared to Lyo HRV was assessed in terms of geometric mean concentrations (GMCs) of anti-RV immunoglobulin A (IgA), 1-month post-second dose (primary objective). Reactogenicity/safety were also evaluated. Seroconversion was defined as anti-RV IgA antibody concentration ≥20 units [U]/mL in initially seronegative infants (anti-RV IgA antibody concentration <20 U/mL) or ≥2-fold increase compared with pre-vaccination concentration in initially seropositive infants. Of the 451 enrolled infants, 381 (189 in Liq HRV and 192 in Lyo HRV group) were included in the per-protocol set. The GMC ratio (Liq HRV/Lyo HRV) was 0.93 (95% confidence interval [CI]: 0.65-1.34), with the lower limit of the 95% CI reaching ≥0.5, the pre-specified statistical margin for non-inferiority. In the Liq HRV and Lyo HRV groups, 42.9% and 44.3% (baseline) and 71.4% and 73.4% (1-month post-second dose) of infants had anti-RV IgA antibody concentration ≥20 U/mL, and overall seroconversion rates were 54.5% and 50.0%. Incidences of solicited and unsolicited adverse events were similar between groups and no vaccine-related serious adverse events were reported. Liq HRV was non-inferior to Lyo HRV in terms of antibody GMCs and showed similar reactogenicity/safety profiles, supporting the use of Liq HRV in Indian infants.

PLAIN LANGUAGE SUMMARYWhat is the context?Rotavirus is the most common cause of acute gastronenteritis and contributes to the high number of hospitalizations and deaths in young children worldwide.Vaccination against rotavirus has led to a significant decrease in rotavirus-related infections.The human rotavirus vaccine Rotarix (GSK) is currently used as a liquid or lyophilized formulation.In clinical trials conducted in European and North American infants, the liquid vaccine showed ability to induce immune response and safety comparable to the lyophilized formulation.Only the lyophilized vaccine is currently marketed in india.What is new?We compared the 2-dose liquid and lyophilized human rotavirus vaccines in indian infants in a phase III clinical trial:The ability to induce immune response for thw liquid formulation was not inferior to that observed for the lyophilized vaccine.The safety profiles of the 2 formulations were comparable.Why is this important?This study shows that the liquid human rotavirus vaccine can be administrated to infants from india.

A phase 4 study of the safety of the 13-valent pneumococcal conjugate vaccine in children 6 to 17 years of age in India.

PURPOSE: The 13-valent pneumococcal conjugate vaccine (PCV13) was recently approved in India for the prevention of pneumococcal disease in children aged 6 to 17 years based on global data as well as immunogenicity and safety findings from a phase 3 study. The current phase 4 study in India further evaluated the safety profile of PCV13 in this age group to support the positive benefit-risk profile of PCV13. METHODS: Healthy male and female children aged 6 to 17 years in India were administered a single intramuscular injection of PCV13. Through 7 days after PCV13 administration, local reactions and systemic events were recorded daily by caregivers in an electronic diary. Adverse events (AEs) were collected from the provision of informed consent through 28-42 days postvaccination. RESULTS: One hundred subjects enrolled in and completed the study. After PCV13 vaccination, 73.9% and 57.8% of subjects reported local reactions and systemic events, respectively. The majority of reactogenicity events were mild to moderate in severity, with injection site pain and fatigue the most frequently reported local reaction and systemic event, respectively. Six subjects reported 7 AEs, all of which were considered unrelated to PCV13. One subject reported a serious AE (acute hepatitis), which was considered unrelated to PCV13 and ultimately resolved. No subjects withdrew because of AEs, and there were no deaths. CONCLUSION: PCV13 vaccination was well tolerated with an acceptable safety profile in healthy subjects aged 6 to 17 years in India. This work further supports the safety profile of PCV13 for prevention of pneumococcal disease in this age group in India.

Long term Immunogenicity of Single Dose of Live Attenuated Hepatitis A Vaccine in Indian Children - Results of 15-Year Follow-up.

OBJECTIVES: To measure anti-HAV antibodies 15 years after a single dose of live attenuated hepatitis A vaccine in Indian children. METHODS: Of the 143 children vaccinated in 2004, 109 were evaluated in 2019, clinically and for anti-HAV antibodies. These children have been assessed clinically every year, and for anti-HAV antibodies in 2004, 2007, 2010 and 2014. RESULTS: Of the 109 children who came for the present assessment, 11 had received additional doses of hepatitis A vaccine in 2004/2007 because of low anti-HAV titre (<20 mIU/mL). In the remaining 98 children, 94 (96%) had seroprotective levels with a geometric mean titre of 79.6 mIU/mL. Seroprotection rate in all 109 children was 86.2%. CONCLUSIONS: Single dose of live attenuated hepatitis A vaccine in Indian children demonstrated robust immunogenicity at 15 years post vaccination.

Clinical study of safety and immunogenicity of pentavalent DTP-HB-Hib vaccine administered by disposable-syringe jet injector in India.

INTRODUCTION: We conducted a randomized, observer-blind, non-inferiority, parallel-group clinical study of diphtheria, tetanus, pertussis, hepatitis B, and Haemophilus influenzae type b conjugate (pentavalent) vaccination of infants in India. Goals were to determine whether the seropositivity rate after vaccination via disposable-syringe jet injector (DSJI) was non-inferior to that via needle and syringe (N-S), and to compare the safety of vaccination by the two methods. METHODS: Healthy children received a three-dose series of vaccine intramuscularly by DSJI or N-S beginning at 6-8 weeks of age. Immunoglobulin G antibody levels were measured by ELISA at 4-6 weeks after the third dose. The main secondary endpoint was safety, measured as injection site and systemic reactions. DISCUSSION: The study was stopped early out of caution beyond that specified in the protocol stopping criteria, after the Data Safety Committee noted a higher frequency of injection site reactions, especially moderate and severe, in the DSJI group. As a result, 128 subjects-DSJI group 61; N-S group 67-completed the study, rather than the 340 planned, and the study was not sufficiently powered to compare immunogenicity endpoints for the groups. Descriptive statistics indicate that seropositivity induced by vaccination with the DSJI was similar to that of N-S for all five antigens. Pentavalent vaccine includes whole-cell pertussis vaccine and an aluminum adjuvant, which may have contributed to the higher number of local reactions with the DSJI. The reactions caused no serious or long-term sequelae, and may be more acceptable in other populations or circumstances.US National Institutes of Health clinical trials identifier: NCT02409095.

Long-term immunogenicity of single dose of live attenuated hepatitis A vaccine in Indian children.

OBJECTIVES: To assess immunogenicity of a single dose of live attenuated hepatitis A vaccine in Indian children, ten years after immunization. METHODS: Of 143 children vaccinated in 2004, 121 children were evaluated in 2014, clinically and for anti-HAV antibodies. RESULTS: 13 children were early vaccine failures who received two doses of HAV vaccine subsequently. 106 (98%) of 108 remaining children had seroprotective levels with a geometric mean titer of 100.5 mIU/mL. On analysis of all 121 children, the immunogenicity was 87.6%. CONCLUSION: Single dose of live attenuated hepatitis A vaccine provides long-term immunity in Indian children.

Safety and immunogenicity of a new purified vero cell rabies vaccine (PVRV) administered by intramuscular and intradermal routes in healthy volunteers.

BACKGROUND: Rabies is 100% fatal but preventable with modern vaccines and immunoglobulins. There is a huge demand for rabies vaccines in developing countries of Asia and Africa. We have developed a new purified vero cell rabies vaccine (PVRV) and evaluated its safety and immunogenicity in healthy volunteers by intramuscular (IM) and intradermal (ID) routes of vaccination. METHODOLOGY: Sixty adults aged between 18 and 50 years were recruited in this actively controlled Phase I clinical study and were randomized to receive three 1 ml or 0.1 ml doses of new PVRV intramuscularly or intradermally on days 0, 7 and 21. The control group received commercially available PVRV (Verorab) by intramuscular route. Adverse events (AEs) were recorded with diary cards till day 28 post-vaccination. Immunogenicity was assessed on day 0, 7, 21 and 42 by rapid fluorescence focus inhibition test (RFFIT). RESULTS: In all, 116 solicited local and systemic events were reported across the three groups. Most were mild and resolved without sequelae. Also the few unsolicited events, deemed unrelated to the study vaccines, caused no problems. No significant changes in the routine laboratory parameters were found. Two doses of a vaccine elicited protective titres (≥ 0.5 IU/ml) in all subjects, the GMTs varying between 0.57 and 0.69 IU/ml on day 7, 3.07 and 3.97 IU/ml on day 21, and 6.12 and 8.52 IU/ml on day 42 post-vaccination. CONCLUSIONS: PVRV was well tolerated and showed good immunogenicity regardless of whether administered intramuscularly or, using a tenth of that volume, intradermally. Further studies with this new vaccine are warranted.

Immunogenicity of two diphtheria-tetanus-whole cell pertussis-hepatitis B vaccines in infants: a comparative trial.

AIM: Because of the high mother-to-infant transmissibility of hepatitis B (HB) infection, neonatal vaccination is necessary, but the further doses of HB vaccines can be combined with conventional diphtheria-tetanus-whole cell pertussis (DTPw) vaccines. We compared immunogenicity and reactogenicity of two tetravalent vaccines in Indian children, who after neonatal HB immunization, were vaccinated thrice with one of these vaccines. METHODS: In this open-label randomized study, 287 infants received a dose of an Indian- (Q-Vac (TM )) or European-made (Tritanrix-HB (TM )) tetravalent vaccine at age 6, 10, and 14 weeks. The ELISA antibodies were measured prior to the first and one month after the third dose. Immunogenicity was determined by measuring the seroprotection/seropositivity rates and geometric mean titres (GMT), whereas vaccine reactogenicity was elucidated with diary cards for 7 days following each dose. The potential unsolicited events were queried throughout the whole 3-month study period. RESULTS: Out of the 250 subjects who completed the study, 123 received the Indian and 127 the European vaccine. After 3 doses, the seroprotection/seropositivity rates were 99 % and 100% for diphtheria, 98% and 95% for tetanus, 89% and 94% for pertussis, and 100% and 100% for hepatitis B, respectively. GMT of tetanus antibodies was significantly higher with the Indian vaccine. Low-grade reactogenicity was rather similar in the two vaccine groups, the most common events being local pain, redness, swelling, fever, irritability, unusual crying, drowsiness, and non-specific gastrointestinal symptoms. CONCLUSIONS: Since both immunogenicity and reactogenicity of the two vaccines were almost identical, the Indian vaccine poses a good alternative to the costlier competitor vaccines.

Immunogenicity of single dose live attenuated hepatitis a vaccine.

A long-term immunogenicity study of a single dose live attenuated H2 strain hepatitis A vaccine is being conducted in healthy Indian children at KEM Hospital, Pune. 131 of the original 143 children vaccinated in 2004, were evaluated for anti-HAV antibodies 30 months post vaccination (2007). Seroprotective antibody levels >20 mIU/mL were demonstrated in 87.8 % subjects with an overall GMT of 92.02 mIU/mL. No hepatitis like illness was recorded in any of the subjects since vaccination.

Immunogenicity and reactogenicity of two recombinant hepatitis B vaccines in small infants: a randomized, double-blind comparative study.

Hepatitis B infection is very common in infants, especially in countries with limited resources. Hepatitis B vaccination is recommended in the routine immunization schedules in many countries, including India. We compared immunogenicity and reactogenicity of two recombinant hepatitis B (HB) vaccines in healthy infants. A total of 262 evaluable Indian infants received three doses of 10 microg of an Indian (GeneVac-B) or European (Engerix-B) HB vaccine in a double-blind, randomized fashion. The first dose, given at birth, was followed by a dose at age 6 and 14 weeks. All the subjects were initially seronegative for HB surface antigen (HBsAg) and anti-HB antibodies (anti-HBs). The post-vaccination anti-HBs titers were assessed by ELISA at the time of second and third dose, and 1 month after the third dose. Seroconversion and seroprotection were defined as anti-HBs titers > or =1 mIU/ml and > or =10 mIU/ml, respectively. After first dose, the seroconversion rates were 20% and 17%, in Indian and European vaccine recipients, respectively. The second and third dose increased the seroconversion to 84% and 80%, and to 98% and 98%, respectively. Correspondingly, the seroprotection rates after the first dose was 11% and 10%, and consequently 54% and 58%, and 97% and 95%. None of the differences between vaccines reached statistically significant proportions. Geometric Mean Titer after third dose was 383 mIU/ml and 285 mIU/ml, respectively, also this difference remaining insignificant. Adverse events were similar in both vaccine groups. Immunogenicity and reactogenicity of the Indian and European Hepatitis B vaccines were comparable, when immunization was started at birth.