Immunogenicity and safety of an indigenously manufactured reconstituted pentavalent (DTwP-HBV+Hib) vaccine in comparison with a foreign competitor following primary and booster immunization in Indian children.

OBJECTIVE: An open label, controlled clinical study was conducted in Indian infants aged 6-14 weeks to compare the immunogenicity and safety of a reconstituted pentavalent vaccine (DTwP-HBV+Hib) of Serum Institute of India Ltd (SIIL) with TritanrixHB+Hiberix vaccine of Glaxo Smithkline (GSK). METHODS: Eligible infants were randomized to receive three doses of the study / comparator vaccine. The vaccines were reconstituted prior to administration, by mixing DTwP-HBV (liquid) with the Hib (lyophilized) vaccine. IgG antibody titres were assessed by ELISA at baseline and after one month following the 3-dose primary immunization schedule. Safety was evaluated after each dose. Further, safety and immunogenicity was also evaluated following a booster dose in the same cohort of children (aged between 15-24 months). SETTING: Tertiary-care hospitals in India Important outcome measures: Immunogenicity and safety following a 3-dose primary vaccination series and a booster vaccination. RESULTS: Post-primary immunization, 100% seroprotection was noted for Diphtheria, Tetanus, Hepatitis B and PRP-Hib components in both the vaccine groups. For pertussis, response was 96.1% in SIIL and 95.4% in GSK group. The overall safety profile as well as persistence of antibodies against all vaccine components up to the time of booster immunization was comparable between the SIIL and GSK groups. A marked rise of all antibody concentrations indicated effective priming. The booster dose was safe, well tolerated with a significant increase in antibody concentrations of all the vaccine antigens in both the groups. CONCLUSION: DTwP-HBV+Hib vaccine of SIIL was found to be safe and immunogenic. This Indian vaccine compared well with the licensed vaccine and is a cost-effective alternative for incorporating into the immunization schedule of various countries so as to control worldwide Hepatitis B and Hib infections.

Sero-Surveillance to Assess Immunity to Rubella and Assessment of Immunogenicity and Safety of a Single dose of Rubella Vaccine in School Girls.

BACKGROUND: Rubella vaccination is not yet included in National Immunization Schedule in India. Serosurvey is frequently used to assess epidemiologic pattern of Rubella in a community. Serosurveys in different parts of India have found that 6-47% of women are susceptible for Rubella infection. The present serosurveillance was conducted in Jammu, India, in two public schools. OBJECTIVE: To determine serological status of Rubella antibodies of school girls and assessment of immunogenicity and reactogenicity of Rubella immunization in seronegative girls. MATERIALS AND METHODS: The current study was conducted to determine Rubella serostatus in peripubertal schoolgirls aged 11-18 years and also to assess immunogenicity and safety of Rubella vaccine (R-Vac) of Serum Institute of India Ltd., Pune, in seronegative girls. For screening, pre-vaccination serum Rubella IgG antibodies were determined and to assess immunogenicity of the vaccine, post-vaccination IgG antibodies were compared with pre-vaccination levels. Safety assessment was done for a period of 8 weeks, post-vaccination. RESULTS: A total of 90 (32.7%) seronegative girls were vaccinated. All girls (100%) became seropositive, post-vaccination. Clinically relevant and statistically significant increase in anti-Rubella IgG titres was observed. The adverse events were mild and self-limiting. CONCLUSIONS: R-Vac vaccine used in the study demonstrated an excellent safety and immunogenicity profile.

Safety and immunogenicity of an indigenously developed Haemophilus influenzae type b conjugate vaccine through various phases of clinical trials.

In view of the need for a cost effective Haemophilus influenzae type b (Hib) conjugate vaccine, a lyophilized vaccine as capsular polysaccharide (PRP) conjugated to tetanus toxoid (Sii HibPRO) was indigenously developed by Serum Institute of India Ltd., Pune (SIIL). From 2004-07, this new vaccine underwent a series of clinical studies before its licensure by National Regulatory Authority (NRA). This paper discusses the results obtained during the clinical development of this vaccine. On finding the vaccine to be safe in animal toxicity studies, a Phase I single dose study was carried out to assess the safety profile of Sii HibPRO in healthy adult male volunteers. Subsequently, in Phase III pre-licensure study, immunogenicity and safety of Sii HibPRO was assessed and compared with Hib tetanus conjugate vaccine (Act-HIB) of Aventis, France. Immunogenicity was evaluated based upon serum anti-PRP IgG antibody concentrations by ELISA at prevaccination and one month each after the second and third dose. Safety was evaluated by recording details of adverse events after each dose of the vaccine. Postvaccination after the third dose, there was 100% seroprotection (anti PRP IgG titre >or= 0.15 microg/ml) in both the groups. Long term protection (>or=1 microg/ml) was achieved in 95.2% and 98.06% infants in Sii HibPRO and Act-HIB groups, respectively. At 15 months, prior to booster dose, 30 children in each group were evaluated and all were found to be seroprotected. Post booster, all of them responded with a strong boost response. Safety of Sii HibPRO was re-established in the post marketing surveillance in which 2,739 doses were administered to 1,029 infants, in 23 cities across India.

Acute and chronic diuretic effect of ethanolic extract of leaves of Cocculus hirsutus (L.) Diles in normal rats.

OBJECTIVES: The objective of this study was to evaluate the acute and chronic diuretic effect of the ethanolic extract of the leaves of Cocculus hirsutus (L.) Diles. METHODS: The ethanolic extract was administered (100, 200 and 400 mg/kg, p.o.) in Wistar rats. In the acute study, rats received drugs orally and urine was collected after 1, 2, 3, 4, 5 and 6 h. The chronic study involved repeated administration of ethanolic extract for 28 days and urine was collected on day 1, 7, 14, 21 and 28. The parameters were total urine volume, concentration of Na+, K+ and Cl- ions, creatinine in urine and serum. Urine output, electrolytes (Na+, K+ and Cl- ions) and creatinine were determined on day 7, 14, 21 and 28. KEY FINDINGS: The highest dose (400 mg/kg) of the ethanolic extract significantly (P < 0.01) enhanced urine output. Excretion of cations (Na+ and K+ ions) and anions (Cl- ions) increased significantly with respect to the control (gum acacia 2% dissolved in saline, 10 ml/kg) group. The increase of cations in the urine after treatment with ethanolic extract was dose dependent. The ethanolic extract of the leaves of C. hirsutus (100, 200 and 400 mg/kg) and furosemide (10 mg/kg) did not significantly change the concentration of Na+, K+ and Cl- ions in serum. The ethanolic extract of the leaves of C. hirsutus (100, 200 and 400 mg/kg) and furosemide (10 mg/kg) increased the excretion of creatinine in urine but with a corresponding decrease in serum. CONCLUSIONS: It was concluded that the ethanolic extract of the leaves of C. hirsutus (400 mg/kg) had significant diuretic effect in rats.

Safety and immunogenicity of diphtheria-tetanus-pertussis vaccine and hepatitis B vaccine as a new tetravalent combination (DTwP/HB) administered alone and at separate sites (DTwP and HB) including comparison with standard commercially available combination vaccine in Indian infants 6-14 weeks of age.

An open, comparative study was conducted at two tertiary care hospitals in India to assess immunogenicity and reactogenicity following administration of the DTwP/HB combination vaccine (Q-Vac) alone and DTwP and HB (Genevac B) vaccines at separate sites. These vaccines manufactured by Serum Institute of India, Ltd. (SIIL), Pune were compared with DTwP/HB vaccine (Tritanrix HB) manufactured by GlaxoSmithKline (GSK) in infants aged 6-14 weeks. The sample size comprised 447 infants who received DTwP/HB vaccine (Group A-150, SIIL) or DTwP and HB (Group B-147, SIIL) vaccines at separate sites or DTPw/HB vaccine (Group C-150, GSK), in a dose of 0.5 ml intra-muscularly. Pre and postvaccination IgG antibodies were determined by ELISA. Postvaccination, in Group A seroprotection was 99.3%, 100%, 96% and 100% to Diphtheria, Tetanus, Pertussis and HBs components respectively. In Group B (n = 147) it was 98.6%, 100%, 95.9% and 99.3% and in Group C (n = 150), it was 96%, 99.3%, 93.3% and 98.6% to D, T, P and HBs component of the vaccine. Postvaccination, geometric mean titres for each component were comparable across three groups by analysis of variance (ANOVA). Adverse events observed were within the range quoted in literature and no Serious Adverse Event (SAE) was observed. Reactogenicity profile in all three groups was comparable. Q-Vac vaccine manufactured by SIIL was found to be safe and immunogenic. Hepatitis B (HB) component did not interfere with the immune response to DTwP components of the vaccine.