A phase III randomized-controlled study of safety and immunogenicity of DTwP-HepB-IPV-Hib vaccine (HEXASIIL®) in infants.

A fully liquid hexavalent containing Diphtheria (D), Tetanus (T) toxoids, whole cell Pertussis (wP), Hepatitis B (Hep B), type 1, 2, 3 of inactivated poliovirus (IPV) and Haemophilus influenzae type b (Hib) conjugate vaccine (DTwP-HepB-IPV-Hib vaccine, HEXASIIL®) was tested for lot-to-lot consistency and non-inferiority against licensed DTwP-HepB-Hib + IPV in an open label, randomized Phase II/III study. In Phase III part, healthy infants received DTwP-HepB-IPV-Hib or DTwP-HepB-Hib + IPV vaccines at 6, 10 and 14 weeks of age. Blood samples were collected prior to the first dose and 28 days, post dose 3. Non inferiority versus DTwP-HepB-Hib + IPV was demonstrated with 95% CIs for the treatment difference for seroprotection/seroconversion rates. For DTwP-HepB-IPV-Hib lots, limits of 95% CI for post-vaccination geometric mean concentration ratios were within equivalence limits (0.5 and 2). Vaccine was well-tolerated and no safety concerns observed.Clinical Trial Registration - CTRI/2019/11/022052.

Immunogenicity and safety of a new quadrivalent HPV vaccine in girls and boys aged 9-14 years versus an established quadrivalent HPV vaccine in women aged 15-26 years in India: a randomised, active-controlled, multicentre, phase 2/3 trial.

BACKGROUND: To meet global cervical cancer elimination efforts, a wider range of affordable and accessible vaccines against human papillomavirus (HPV) are needed. We aimed to evaluate the immunogenicity and safety of a quadrivalent HPV vaccine (targeting HPV types 6, 11, 16, and 18), developed and manufactured by the Serum Institute of India (SIIPL). Here we report outcomes in the 9-14 years cohort. METHODS: This randomised, active-controlled, phase 2/3 trial was conducted at 12 tertiary care hospitals across India. Healthy participants aged 9-14 years or 15-26 years with no history of HPV vaccination were eligible for enrolment. Female participants were randomly assigned (1:1) with an interactive web response system, by use of a central computer-generated schedule and block randomisation (block sizes of 2, 4, 6, and 8), to receive the SIIPL quadrivalent HPV vaccine (Cervavac; SIIPL, Pune, India) or the comparator quadrivalent HPV vaccine (Gardasil; Merck Sharp & Dohme, Harleem, the Netherlands). Participants, investigators, laboratory technicians, and sponsors were masked to treatment allocation of female participants. Male participants were given the SIIPL quadrivalent HPV vaccine in an open-label manner. Study vaccines were administered intramuscularly with a two-dose schedule (at day 0 and 6 months) in the cohort aged 9-14 years, and with a three-dose schedule (at day 0, month 2, and month 6) in the cohort aged 15-26-years. Immunogenicity was assessed 30 days after the last dose by use of multiplexed ELISA. The primary outcome was the non-inferiority of immune response in terms of the geometric mean titre (GMT) of antibodies against HPV types 6, 11, 16, and 18 generated by the SIIPL quadrivalent HPV vaccine in girls and boys (aged 9-14 years) compared with the GMT generated by the comparator quadrivalent HPV vaccine in women aged 15-26 years at month 7 in the modified per-protocol population (ie, all participants who received all doses of study vaccines per assigned treatment group and had both day 0 and 1-month immunogenicity measurements after the last dose following protocol-defined window periods with no major protocol deviations). Non-inferiority was established if the lower bound of the 98·75% CI of the GMT ratio was 0·67 or higher. The co-primary outcome of occurrence of solicited adverse events (within 7 days of each dose) and unsolicited adverse events (up to 30 days after the last dose) was assessed in all participants who were enrolled and received at least one dose of study vaccine. The trial is registered with the Clinical Trials Registry - India (CTRI/2018/06/014601), and long-term follow-up is ongoing. FINDINGS: Between Sept 20, 2018, and Feb 9, 2021, 2341 individuals were screened, of whom 2307 eligible individuals were enrolled and vaccinated: 1107 (738 girls and 369 boys) in the cohort aged 9-14 years and 1200 (819 women and 381 men) in the cohort aged 15-26 years. No race or ethnicity data were collected. 350 girls and 349 boys in the SIIPL quadrivalent HPV vaccine group and 338 women in the comparator vaccine group were included in the modified per-protocol population for the primary endpoint analysis. The median follow-up for the analyses was 221 days (IQR 215-231) for girls and 222 days (217-230) for boys in the SIIPL quadrivalent HPV vaccine group, 223 days (216-232) for girls in the comparator vaccine group, and 222 days (216-230) for women in the comparator vaccine group. GMT ratios were non-inferior in girls and boys receiving the SIIPL quadrivalent HPV vaccine compared with women receiving the comparator vaccine: GMT ratios for girls were 1·97 (98·75% CI 1·67-2·32) for HPV type 6, 1·63 (1·38-1·91) for HPV type 11, 1·90 (1·60-2·25) for HPV type 16, and 2·16 (1·79-2·61) for HPV type 18. For boys the GMT ratios were 1·86 (1·57-2·21) for HPV type 6, 1·46 (1·23-1·73) for HPV type 11, 1·62 (1·36-1·94) for HPV type 16, and 1·80 (1·48-2·18) for HPV type 18. The safety population comprised all 1107 participants (369 girls and 369 boys in the SIIPL quadrivalent HPV vaccine group, and 369 girls in the comparator group). Solicited adverse events occurred in 176 (48%) of 369 girls and 124 (34%) of 369 boys in the SIIPL vaccine group and 179 (49%) of 369 girls in the comparator vaccine group. No grade 3-4 solicited adverse events occurred within 7 days of each dose. Unsolicited adverse events occurred in 143 (39%) girls and 147 (40%) boys in the SIIPL vaccine group, and 143 (39%) girls in the comparator vaccine group. The most common grade 3 unsolicited adverse event was dengue fever, in one (<1%) girl in the SIIPL vaccine group and three (1%) girls in the comparator group. There were no grade 4 or 5 adverse events. Serious adverse events occurred in three (1%) girls and three (1%) boys in the SIIPL vaccine group, and five (1%) girls in the comparator vaccine group. No vaccine-related serious adverse events were reported. There were no treatment-related deaths. INTERPRETATION: We observed a non-inferior immune response with the SIIPL quadrivalent HPV vaccine in girls and boys aged 9-14 years and an acceptable safety profile compared with the comparator vaccine. These findings support extrapolation of efficacy from the comparator vaccine to the SIIPL quadrivalent HPV vaccine in the younger population. The availability of the SIIPL quadrivalent HPV vaccine could help meet the global demand for HPV vaccines, and boost coverage for both girls and boys globally. FUNDING: Biotechnology Industry Research Assistance Council, Department of Biotechnology (DBT), Government of India, and Serum Institute of India.

Safety and immunogenicity of SIIPL Tdap, a new tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine, in healthy subjects 4-65 years of age: A Phase II/III randomized, observer-blinded, active controlled, multicenter clinical study in Germany.

BACKGROUND: This study assessed the safety and immunogenicity of a new booster vaccine against tetanus, diphtheria, and pertussis manufactured by Serum Institute of India Pvt. Ltd (SIIPL Tdap). METHODS: The Phase II/III trial was randomized (2:1), observer blinded and active controlled. Healthy subjects aged 4-65 years received a single dose of either SIIPL Tdap or comparator Tdap vaccine (Boostrix®, GlaxoSmithKline, Belgium), and were followed-up for 30 days. Blood samples for safety and immunogenicity assessments were collected pre-vaccination and on day 30 post-vaccination. The study assessed safety and reactogenicity of SIIPL Tdap compared to the comparator Tdap as well as the co-primary immunogenicity outcomes: (i) seroprotection rates against diphtheria toxoid (DT) and tetanus toxoid (TT) and (ii) the booster response rates against pertussis toxoid (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) 30 days post-vaccination in all study subjects. A margin of -10 % was used for non-inferiority testing. Secondary outcomes included the booster response rates against DT and TT, seropositivity rates against pertussis antigens, and antibody geometric mean concentrations (GMCs) for all vaccine components. RESULTS: At Day 30 post-vaccination, SIIPL Tdap was assessed as non-inferior to the comparator Tdap in terms of: i) seroprotection rates against DT (94.4 % vs. 94.9 %) and TT (99.9 % vs. 100 %) and ii) pertussis booster response rates (93.8 % vs. 88.4 % anti-PT, 89.7 % vs. 90.9 % anti-FHA and 86.3 % vs. 84.4 % anti-PRN), for SIIPL Tdap versus comparator Tdap, respectively. GMCs for anti-PT and anti-PRN were higher in subjects vaccinated with SIIPL Tdap compared to comparator Tdap. All other secondary outcomes were comparable. The overall frequency of local and systemic solicited AEs was comparable; no treatment related SAEs were reported. CONCLUSIONS: Booster vaccination with SIIPL Tdap was non-inferior to comparator Tdap with respect to the immunogenicity of the vaccine components and was equally well tolerated. EudraCT number: 2019-002706-46.

Multiplexed bead-based assay for the simultaneous quantification of human serum IgG antibodies to tetanus, diphtheria, pertussis toxin, filamentous hemagglutinin, and pertactin.

Background: Luminex bead-based assays offer multiplexing to test antibodies against multiple antigens simultaneously; however, this requires validation using internationally certified reference standards. Therefore, there is an urgent need to characterize existing reference standards for the standardization of multiplex immunoassays (MIAs). Here, we report the development and validation of an MIA for the simultaneous estimation of levels of human serum immunoglobulin G (IgG) antibodies for pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), diphtheria toxoid (DT), and tetanus toxoid (TT). Methods: The MIA was assessed using a panel of human serum samples and WHO reference standards. The WHO reference standards were also studied for suitability in the MIA. Purified antigens (PT, FHA, PRN, DT, and TT) were coupled to the spectrally unique magnetic carboxylated microspheres. The method was validated in accordance with the United States Food and Drug Administration (US FDA), European Medicines Agency (EMA), and the International Committee of Harmonization Multidisciplinary (ICH M10) guidelines, and parameters such as precision, accuracy, dilutional linearity, assay range, robustness, and stability were assessed. Method agreements with commercially available IgG enzyme-linked immunosorbent assay (ELISA) assays were also evaluated. In addition, the study assessed the level of correlation between the IgG levels estimated by the MIA and the cell-based neutralizing antibody assays for PT and DT. Results: We identified that an equimix of WHO international standards (i.e., 06/142, 10/262, and TE-3) afforded the best dynamic range for all the antigens in the MIA. For all five antigens, we observed that the back-fitted recoveries using the four-parameter logistic (4-PL) regression fits ranged between 80% and 120% for all calibration levels, and the percentage coefficient of variation (% CV) was < 20%. In addition, the difference in mean fluorescence intensity (MFI) between the monoplex and multiplex format was < 10% for each antigen, indicating no crosstalk among the beads. The MIA also showed good agreement with conventional and commercially available assays, and a positive correlation (> 0.75) with toxin neutralization assays for PT and DT was observed. Conclusion: The MIA that was calibrated in accordance with WHO reference standards demonstrated increased sensitivity, reproducibility, and high throughput capabilities, allowing for the design of robust studies that evaluate both natural and vaccine-induced immunity.

A Phase I study to evaluate safety and tolerability of DTaP-IPV + Hib vaccine in healthy adult volunteers in India.

Background: To assess safety and tolerability of a diphtheria and tetanus toxoid, acellular pertussis, inactivated poliovirus and Haemophilus influenza type B conjugate adsorbed vaccine (DTaP-IPV + Hib), manufactured by Serum Institute of India Pvt. Ltd. (SIIPL)'s, the current first-in-human Phase 1 study was conducted in healthy adults. Methods: Vaccine was administered as a single 0.5 mL dose intramuscularly into deltoid muscle of 24 healthy adults aged 18-45 years, who were then followed prospectively for one month for safety outcomes. Results: All 24 participants completed the study in compliance with protocol. Four solicited adverse events were reported in three participants during the study; all adverse events were mild and recovered completely. No deaths, unsolicited adverse events, or serious adverse events were reported. Conclusion: SIIPL DTaP-IPV + Hib vaccine was well tolerated and safe in study subjects. Further clinical development will be conducted to assess safety and immunogenicity in young children, the target population.Clinical Trial Registration: CTRI/2017/07/009034.

A phase-I, open label clinical trial to assess the safety & tolerability of qHPV vaccine manufactured by Serum Institute of India Pvt. Ltd. in adults.

Background: This first in human study was designed as an open label clinical trial to assess safety and tolerability of Serum Institute of India Pvt. Ltd. (SIIPL) quadrivalent HPV (qHPV) vaccine. Methods: A total of 48 healthy male and female (24 each) adult volunteers were administered a 0.5 ml single dose of SIIPL qHPV vaccine intramuscularly, and were followed for one month for safety outcomes viz., immediate, solicited, unsolicited and serious adverse events. Results: 47 subjects completed the study in compliance with protocol. One subject had pain immediately after immunization which was recovered without treatment. None of the participants experienced any other local or systemic solicited AEs and serious AE. Conclusion: qHPV vaccine manufactured by SIIPL was found to be safe and well tolerable in adults. Further clinical development should continue to assess safety and immunogenicity, in the target population following recommended 2 and 3-dose schedule.Clinical Trial Registration - CTRI/2017/02/007785.

Safety and immunogenicity of an indigenously developed tetanus toxoid, diphtheria toxoid, and acellular pertussis vaccine (Tdap) in adults, adolescents, and children in India.

BACKGROUND: This study assessed safety and immunogenicity of Serum Institute of India Pvt Ltd (SIIPL)'s tetanus toxoid (TT), diphtheria toxoid (DT), and acellular pertussis booster vaccine (Tdap). RESEARCH DESIGN AND METHODS: In this Phase II/III, multicenter, randomized, active-controlled, open-label study, 1500 healthy individuals, aged 4-65 years, were randomized to receive a single dose of SIIPL Tdap or comparator Tdap vaccine (Boostrix®; GlaxoSmithKlines, India). Adverse events (AEs) during initial 30 minutes, 7-day, 30-day post-vaccination were assessed. Blood samples were taken before and 30 days post-vaccination for immunogenicity assessment. RESULTS: No significant differences in incidence of local and systemic solicited AEs were observed between the two groups; no vaccine-related serious AEs were reported. SIIPL Tdap was non-inferior to comparator Tdap in achieving booster responses to TT and DT in 75.2% and 70.8% of the participants, respectively, and to pertussis toxoid (PT), pertactin (PRN), and filamentous hemagglutinin (FHA) in 94.3%, 92.6%, and 95.0% of the participants, respectively. Anti-PT, anti-PRN, and anti-FHA antibody geometric mean titers in both the groups, were significantly higher post-vaccination compared to pre-vaccination. CONCLUSIONS: Booster vaccination with SIIPL Tdap was non-inferior to comparator Tdap with respect to immunogenicity against tetanus, diphtheria, and pertussis and was well tolerated.

VPM1002 as Prophylaxis Against Severe Respiratory Tract Infections Including Coronavirus Disease 2019 in the Elderly: A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Study.

BACKGROUND: Bacille Calmette-Guérin (BCG) vaccination can potentially reduce the rate of respiratory infections in vulnerable populations. This study evaluates the safety and efficacy of VPM1002 (a genetically modified BCG) as prophylaxis against severe respiratory tract infections including coronavirus disease 2019 (COVID-19) in an elderly population. METHODS: In this phase 3, randomized, double-blind, placebo-controlled, multicenter clinical trial, healthy elderly volunteers (N = 2064) were enrolled, randomized (1:1) to receive either VPM1002 or placebo, and followed up remotely for 240 days. The primary outcome was the mean number of days with severe respiratory infections at hospital and/or at home. Secondary endpoints included the incidence of self-reported fever, number of hospital and intensive care unit (ICU) admissions, and number of adverse events. RESULTS: A total of 31 participants in the VPM1002 group reported at least 1 day with severe respiratory disease and a mean number of days with severe respiratory disease of 9.39 ± 9.28 while in the placebo group; 38 participants reported a mean of 14.29 ± 16.25 days with severe respiratory disease. The incidence of self-reported fever was lower in the VPM1002 group (odds ratio, 0.46 [95% confidence interval, .28-.74]; P = .001), and consistent trends to fewer hospitalization and ICU admissions due to COVID-19 were observed after VPM1002 vaccination. Local reactions typical for BCG were observed in the VPM1002-vaccinated group, which were mostly of mild intensity. CONCLUSIONS: Vaccination with VPM1002 is well tolerated and seems to have a prophylactic effect against severe respiratory disease in the elderly. CLINICAL TRIALS REGISTRATION: NCT04435379.

A phase I, open label, clinical study to assess the safety and immunogenicity of indigenously developed liquid (DTwP-HepB-IPV-Hib) hexavalent combination vaccine in healthy toddlers aged 16-24 months.

This first in human study was designed as an open label clinical trial to assess the safety and immunogenicity of SIIPL DTwP-HepB-IPV-Hib (Hexavalent) combination vaccine in healthy toddlers, aged 16-24 months. A total of 24 healthy toddlers were administered a 0.5 ml single dose of SIIPL DTwP-HepB-IPV-Hib vaccine intramuscularly, and followed for 28 days for safety outcomes viz. immediate, solicited, unsolicited and serious adverse events. Blood samples were collected immediately prior to and 28 days after vaccination to assess the immunogenicity. Twenty four completed the study in compliance with the study protocol. None of the participants experienced any immediate or any serious adverse event. In terms of the frequency and intensity, the adverse events were comparable to DTwP-based combination vaccines. The vaccine elicited a strong booster response as demonstrated by a large increase in antibodies against all vaccine antigens. One month post booster vaccination seroprotection for diphtheria, tetanus, Hepatitis B, Haemophilus influenzae type b and polio virus type 1 and 3 was 100%. The percentage sero-response for pertussis was 75%. Four-fold increase in antibody concentration for pertussis was achieved in 87.5% subjects. Indigenously developed DTwP-HepB-IPV-Hib vaccine by Serum Institute of India Pvt. Ltd. was found to be safe, well tolerated and showed a robust immune response in toddlers. It was concluded that this vaccine should be assessed in the next phases of clinical development in the target population.Clinical Trial Registration - CTRI/2018/10/015875.

A phase-I, open label clinical trial to assess the safety of Tdap vaccine manufactured by Serum Institute of India Pvt. Ltd. in adults.

BACKGROUND: This first in human study was designed as an open label clinical trial to assess the safety and tolerability of Serum Institute of India Pvt. Ltd. (SIIPL) Tdap vaccine in healthy adult volunteers, aged 18-45 years. METHODS: A total of 24 healthy adults were administered a 0.5 ml single dose of SIIPL Tdap vaccine intramuscularly, and were followed for one month for safety outcomes viz., immediate, solicited, unsolicited and serious adverse events. RESULTS: 23 subjects completed the study in compliance with the study protocol. None of the participants experienced any immediate adverse events or any local or systemic solicited adverse events. CONCLUSION: Tdap vaccine manufactured by Serum Institute of India Pvt. Ltd. is safe and well tolerable in adults. It was concluded that further clinical development of this vaccine should continue to assess its safety and immunogenicity, in the target population. Clinical Trial Registration - CTRI/2017/03/008003.

Vaccines For Type 1 Diabetes: Prevention or Reversal?

Type 1 diabetes mellitus (T1DM) is an autoimmune disease which leads to the destruction of pancreatic ß-cells, thereby causing insufficient insulin production. Globally, around 98, 200 children and adolescents below 15 years of age and almost 128,900 subjects below 20 years of age develop T1DM annually, along with severe complications deteriorating their quality of life. In India alone, around 15,900 incident cases below 15 years have reported annually. Hence, its prevention and reversal are significant. Unlike other chronic diseases, T1DM involves the presence of various autoantigens, which can be targeted by proper immunisation. The development of reliable immuno-regulatory surrogate markers would be of great benefit. Vaccines can be one of such strategies in the journey to prevent T1DM. It would not only benefit greatly to reduce the sufferings caused due to diabetic complications but could also help to reverse T1DM, by modulating the autoantigenic immunological reactions and prevent further degradation of pancreatic ß-cells. This review collates a wide range of information related to the vaccine studies conducted in animal and human models to prevent and reverse T1DM.

Results of the phase I open label clinical trial SAKK 06/14 assessing safety of intravesical instillation of VPM1002BC, a recombinant mycobacterium Bacillus Calmette Guérin (BCG), in patients with non-muscle invasive bladder cancer and previous failure of conventional BCG therapy.

Background: VPM1002BC is a modified mycobacterium Bacillus Calmette Guérin (BCG) for the treatment of non-muscle invasive bladder cancer (NMIBC). The genetic modifications are expected to result in better immunogenicity and less side effects. We report on patient safety and immunology of the first intravesical application of VPM1002BC in human. Methods: Six patients with BCG failure received a treatment of 6 weekly instillations with VPM1002BC. Patients were monitored for adverse events (AE), excretion of VPM1002BC and cytokines, respectively. Results: No DLT (dose limiting toxicity) occurred during the DLT-period. No grade ≥3 AEs occurred. Excretion of VPM1002BC in the urine was limited to less than 24 hours. Plasma levels of TNFα significantly increased after treatment and blood-derived CD4+ T cells stimulated with PPD demonstrated significantly increased intracellular GM-CSF and IFN expression. Conclusion: The intravesical application of VPM1002BC is safe and well tolerated by patients and results in a potential Th1 weighted immune response.

A prospective comparative study to assess the efficacy and tolerability of 2 different doses of intravesical bacillus Calmette-Guerin (BCG) in patients with non-muscle-invasive bladder cancer.

BACKGROUND: Bacillus Calmette-Guerin (BCG) is widely used as an immunotherapeutic agent and recommended in management of non-muscle-invasive bladder cancer (NMIBC). There is no consensus on the optimal dose of the BCG. However, dose reduction has been assessed to decrease the side effects following instillation of BCG. This study compared the efficacy and safety of 80 and 120 mg doses of Sii Onco BCG (Moscow I, Russian strain) in patients with NMIBC. METHODS: Patients with histologically confirmed, completely resected solitary or multiple Ta or T1 (with or without carcinoma in situ), grade 1 to 3 urothelial carcinoma of the bladder were included. After transurethral resection of the tumor, repeated intravesical instillations with Sii Onco BCG (80 or 120 mg) were administered, following the induction and 3 weekly maintenance schedule (at 3, 6, 9, 15, 21, 27, and 33 months). Recurrence and progression of the tumor were monitored at scheduled time intervals using cystoscopy. RESULTS: A total of 104 eligible patients were enrolled to receive 80 mg (n = 51) dose or 120 mg dose (n = 53) of Sii Onco BCG. On completion of 3 years follow-up, recurrence-free survival rate of 84.31% and 86.79% and progression-free survival rate of 84.31% and 94.34% were observed for 80 and 120 mg groups, respectively; difference being statistically nonsignificant. CONCLUSION: Both, 80 and 120 mg doses of Sii Onco BCG are effective and safe for prophylaxis and management of NMIBC.

Post-marketing surveillance study to assess the safety and tolerability of an Inactivated Poliomyelitis Vaccine in Indian children.

OBJECTIVE: To evaluate the incidence of adverse events following administration of an Inactivated poliomyelitis vaccine (IPV) manufactured by Serum Institute of India Pvt. Ltd., Pune, India. METHODS: A single 0.5 ml dose of the IPV was administered intramuscularly to children attending private clinics or out-patient department of hospitals for routine immunization across different cities in India. They were observed over a period of 30 d for local or systemic adverse events and rare case of anaphylaxis, if any. RESULTS: A total of 2210 children were enrolled of which 2120 children received the vaccine within primary immunization series and 90 children received booster dose. The common adverse events reported were pain, erythema, swelling and fever. No serious adverse event was reported during the study period. CONCLUSIONS: Poliomyelitis vaccine (Inactivated) manufactured by Serum Institute of India Pvt. Ltd., Pune can be safely administered to children following the Expanded Programme on Immunization or World Health Organization recommended immunization schedule.

Sero-surveillance to assess rubella susceptibility and assessment of immunogenicity and reactogenicity of rubella vaccine in Indian girls aged 18-24 years.

Rubella infection though a mild infection, may cause foetal death or a variety of congenital anomalies. Multiple sero-surveys confirmed that 5-10% women are unexposed to natural or vaccinated rubella virus and remain susceptible to rubella infection. The current study was conducted in 600 girls, aged 18-24 y from Symbiosis International University (SIU), Pune, India to assess their sero-status against rubella infection and to estimate the immunogenicity of rubella vaccine in achieving sero-protective antibody titres. Prior to administration of a single i.m. dose of rubella vaccine (R-vac®) to eligible participants, blood sample (pre-vaccination) was collected. During the 4-6 weeks observation period, adverse events were noted. Then, a second blood sample (post-vaccination) was collected. Significant increase was noted in sero-protection response, viz., 98.6% (post-vaccination) vis-à-vis 66.5% (pre-vaccination); Geometric mean titer (GMT) was significantly higher post-vaccination. Effective measures to introduce rubella vaccination on a larger scale need to be undertaken. An immunization policy with mandatory rubella vaccination for all girls in the reproductive age group and its inclusion in national immunization schedule is highly desirable.

Antibody persistence of two pentavalent DTwP-HB-Hib vaccines to the age of 15-18 months, and response to the booster dose of quadrivalent DTwP-Hib vaccine.

OBJECTIVES: Antibody persistence in children following three doses of primary vaccination with diphtheria, tetanus, whole-cell-pertussis (DTwP), hepatitis B, and Haemophilus influenzae type b (Hib) vaccines (SIIL Pentavac vaccine vs. Easyfive(®) of Panacea Biotec), and response to the booster dose of DTwP-Hib (Quadrovax(®)) vaccine. METHODS: Children who completed their primary immunization were assessed for antibodies at 15-18 months of age, and then given a booster dose of DTwP-Hib vaccine. Reactogenicity and safety of the booster dose was evaluated. RESULTS: Both pentavalent vaccines demonstrated a good immune response at 15-18 months. Following the booster dose, all vaccinated subjects achieved protective titers against diphtheria, tetanus and Hib, whereas the response to pertussis antigen was ~78%. Fever and irritability was noted in 24%, local pain in 51%, and swelling in 36% of the children following booster dose. CONCLUSIONS: Primary immunization with either pentavalent vaccine induced an excellent immunity lasting till the second year of life. A booster dose with DTwP-Hib (Quadrovax(®)) vaccine effectuated a good anamnestic response to all vaccine components, being specially strong for Hib in children previously vaccinated with SIIL liquid pentavalent vaccine (Pentavac(®)). Also, the safety profile of SIIL quadrivalent vaccine (Quadrovax(®)) administered as booster dose was acceptable.

A phase III, randomized controlled study to assess the safety and immunogenicity of a semi-synthetic diphtheria, tetanus and whole-cell pertussis vaccine in Indian infants.

BACKGROUND: Reactions to DTwP vaccine are well known and are a matter of great concern, much for the development of next generation combination vaccines. To avoid such reactions which occur from foreign compounds, WHO suggested manufacture of DTwP vaccine using semi-synthetic medium. The phase III trial reported here was conducted to assess the immunogenicity, tolerability and safety of a new DTwP vaccine manufactured using semi-synthetic medium for both tetanus and diphtheria toxoids in comparison with the routinely manufactured DTwP vaccine. METHODS: In all, 331 infants aged 6-8 weeks were enrolled, out of which 308 completed the study. The vaccination was done at 6-10-14 weeks following EPI/WHO recommended immunization schedule. Blood samples were collected prior to the administration of first dose and one month after the third dose. RESULTS: Postvaccination, geometric mean titres for each component did not differ significantly amongst the two study groups. Though, the immunogenicity results were comparable between the two vaccines, the incidence of adverse events was comparatively low in semi-synthetic vaccine as against the routine vaccine group for all the three doses. CONCLUSIONS: The semi-synthetic DTwP vaccine was immunogenic and showed a significant lower incidence of local adverse events in comparison to the routine vaccine. This vaccine is now being used in the routine vaccination programme both as a triple antigen (DTwP alone) as well as a combination with Hepatitis B and/or Haemophilus influenzae type b vaccine.

Assessment of safety and immunogenicity of two different lots of diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae type b vaccine manufactured using small and large scale manufacturing process.

BACKGROUND: Hib vaccine can be easily incorporated in EPI vaccination schedule as the immunization schedule of Hib is similar to that of DTP vaccine. To meet the global demand of Hib vaccine, SIIL scaled up the Hib conjugate manufacturing process. This study was conducted in Indian infants to assess and compare the immunogenicity and safety of DTwP-HB+Hib (Pentavac(®)) vaccine of SIIL manufactured at large scale with the 'same vaccine' manufactured at a smaller scale. METHODS: 720 infants aged 6-8 weeks were randomized (2:1 ratio) to receive 0.5 ml of Pentavac(®) vaccine from two different lots one produced at scaled up process and the other at a small scale process. Serum samples obtained before and at one month after the 3rd dose of vaccine from both the groups were tested for IgG antibody response by ELISA and compared to assess non-inferiority. RESULTS: Neither immunological interference nor increased reactogenicity was observed in either of the vaccine groups. All infants developed protective antibody titres to diphtheria, tetanus and Hib disease. For hepatitis B antigen, one child from each group remained sero-negative. The response to pertussis was 88% in large scale group vis-à-vis 87% in small scale group. Non-inferiority was concluded for all five components of the vaccine. No serious adverse event was reported in the study. CONCLUSIONS: The scale up vaccine achieved comparable response in terms of the safety and immunogenicity to small scale vaccine and therefore can be easily incorporated in the routine childhood vaccination programme.

Seroprevalence of rubella and immunogenicity following rubella vaccination in adolescent girls in India.

INTRODUCTION: Serologic surveys conducted in different countries indicate that rubella is a worldwide infection. Several such sero surveys conducted in India have also confirmed that 6-47% of women are susceptible to rubella infection. The current study was conducted on 1,329 female adolescents in 12 districts of Maharashtra, India, to assess their serological status in terms of rubella exposure. METHODOLOGY: After enrollment, a pre-vaccination blood sample was collected from the participants followed by rubella vaccination (R-vac). Adverse events were monitored for the next 6-8 weeks, at which time a post-vaccination sample was collected. RESULTS: Pre-vaccination rubella immunity was higher in the urban (80.2%) population compared to the rural (73.1%) population. Following R-vac vaccination, out of 1,159 participants who completed the study, all (100%) in the urban and 99.5% of participants in the rural area developed antibodies against rubella. CONCLUSION: Substantial numbers of women reach childbearing age without immunity against rubella and thus are at a risk of passing the infection to their fetuses, who can then develop subsequent congenital defects leading to congenital rubella syndrome (CRS). An immunization policy recommending vaccination with rubella or rubella containing vaccine is highly desirable to prevent rubella and CRS.