Stability of lyophilized Meningococcal A conjugate vaccine, (MenAfriVac™) at elevated temperatures to support controlled temperature chain (CTC) claim.

Meningococcal A Conjugate Vaccine (MenAfriVac) is the world's first Monovalent Conjugate Vaccine against Neisseria Meningitidis serogroup A which has obtained Controlled Temperature Chain (CTC) label claim of "stable upto 40°C for 4 days prior to reconstitution" developed by Serum Institute of India Pvt. Ltd. Pune, India and the vaccine was granted permission from World health Organization. This paper elucidates and talks about the layout of various studies performed to characterize the product to declare as CTC at the time when the knowledge and mechanism to describe CTC was not fully known which in term helped to design the CTC guidelines. Product stability was assessed using clinical, consistency and regular lots released by NRA. The critical stability indicating parameters like free polysaccharide, molecular size distribution along with Potency and safety tests were carried out to support the product stability making sure it also qualifies for Vaccine Vial Monitor label claim of VVM30. An additional in use stability (reconstitution) was also performed. All studies indicated that the product remains stable at real time as well as elevated temperatures and well within the specifications approved by NRA and formed the strong basis for CTC claim which is now recommended by WHO.

Development and application of HPLC-RI and HPLC-MS/MS based methods for quantification of residual deoxycholate levels in pneumococcal polysaccharides.

The analysis of residual sodium deoxycholate (DOC); a detergent of biological origin used in manufacturing of polysaccharide vaccines is challenging due to complex sample matrices and the lack of suitable methods. Here we report, rapid and sensitive high-performance liquid chromatography-refractive index (HPLC-RI) and tandem mass spectrometry (HPLC-MS/MS) methods for estimation of residual DOC in pneumococcal polysaccharides. For HPLC-RI method, separation was achieved using Luna C18 column and mobile phase compositions of acetonitrile: methanol: 20 mM sodium acetate (60:05:35% v/v). For HPLC-MS/MS method, separation was achieved using a Hypersil BDS C18 column with gradient elution of methanol and water (0.1% formic acid). MS/MS method showed linearity (r2 = 0.997) over the range of 10-320 ng/mL with limits of detection (LOD) and lower limit of quantitation (LOQ) of 3 and 10 ng/mL respectively. Precision (% RSD) and accuracy (% recovery) for both methods were in the range of 0.74-8.29% and 82.33-117.86% respectively. Sample matrices interferences were addressed following novel sample clean-up method based on liquid-liquid extraction. Both methods enabled traceable quantitation of DOC in intermediate and purified pneumococcal polysaccharides of serotypes: 1, 5, 6A, 6B, 7F, 9V, 14, 19A, 19F and 23F.

Regulatory Pathways That Facilitated Timely Registration of a New Group A Meningococcal Conjugate Vaccine for Africa's Meningitis Belt Countries.

BACKGROUND: Through its normative and public health leadership roles, the World Health Organization (WHO) plays a key role in the availability of vaccine products in low-and middle-income countries. The recent introduction of a new group A meningococcal conjugate vaccine, PsA-TT (MenAfriVac), in Africa exemplifies this process. WHO requires that any new vaccine to be introduced in countries for public health reasons and supplied through United Nations centralized mechanisms be licensed by the national regulatory agency (NRA) in the producing country, then prequalified and given a marketing authorization in the user countries. METHODS: PsA-TT was manufactured by the Serum Institute of India, Ltd (SIIL), which submitted a license application in April 2009 to the Drug Controller General of India (DCGI), the Indian NRA responsible for licensing vaccines. WHO encouraged the DCGI to establish a collaboration with Health Canada's Centre for Vaccine Evaluation for the review. Through this collaborative effort, registration was facilitated and in December 2009 an export license was granted to SIIL, which subsequently submitted an application for WHO prequalification. RESULTS: Given the importance of the vaccine, WHO "fast tracked" the prequalification review, and after a detailed review and site visit, WHO prequalification was granted to PsA-TT in June 2010. Country use of the new vaccine could not occur until the vaccine was a registered product in each country seeking its use. WHO facilitated country reviews by conducting regulatory training exercises (in French and English) for country NRA staff, which used the PsA-TT registration as a case study. CONCLUSIONS: PsA-TT was gradually registered in African countries as vaccine introduction proceeded. The regulatory pathway for this new group A meningococcal conjugate vaccine proved to be a useful training opportunity both in India and Africa, because the availability of the vaccine was a high African public health priority, as well as for WHO as a case study to facilitate registration of vaccines based on reliance on other regulatory bodies.

Challenges and Opportunities While Developing a Group A Meningococcal Conjugate Vaccine Within a Product Development Partnership: A Manufacturer's Perspective From the Serum Institute of India.

BACKGROUND: In 2002, the Meningitis Vaccine Project (MVP) chose the Serum Institute of India, Ltd (SIIL), as its manufacturing partner to establish a product development partnership (PDP) with the Meningitis Vaccine Project (MVP). MVP was a collaboration between PATH and the World Health Organization (WHO) to develop meningococcal conjugate vaccines for sub-Saharan Africa. METHOD: From the outset, SIIL recognized that a partnership with MVP carried some risk but also offered important opportunities for accessing new conjugate vaccine technology and know-how. Over 3 years, SIIL successfully accepted technology transfer for the group A meningococcal polysaccharide from SynCo Bio Partners and a conjugation method from the US Food and Drug Administration. RESULTS: SIIL successfully scaled up production of a group A meningococcal conjugate vaccine that used SIIL tetanus toxoid as the carrier protein. Phase 1 studies began in India in 2005, followed by phase 2/3 studies in Africa and India. A regulatory dossier was submitted to the Indian authorities in April 2009 and WHO in September 2009. Export license was granted in December 2009, and WHO prequalification was obtained in June 2010. Vaccine was introduced at public scale in Burkina Faso that December. The group A meningococcal conjugate vaccine was named MenAfriVac, and is the first internationally qualified vaccine developed outside of big pharma. CONCLUSIONS: The project proved to be a sound investment for SIIL and is a concrete example of the potential for PDPs to provide needed products for resource-poor countries.

HPLC/tandem mass spectrometric studies on steroidal saponins: an example of quantitative determination of Shatavarin IV from dietary supplements containing Asparagus racemosus.

Asparagus racemosus (AR) is a popular botanical present in several Ayurvedic medicines and nutritional and dietary supplements with immunomodulatory, galactogogue, and anticancer activity. A steroidal saponin known as shatavarin IV is one of the active constituents of AR. A new, selective, and rapid HPLC/MSIMS method has been developed and validated for quantitative estimation of shatavarin IV in crude, processed, and marketed samples of AR. The analytes were separated on a Luna C18 column using simple isocratic elution with water (0.1% acetic acid)-acetonitrie;(0.1% acetic acid; 70 + 30, vIv) at a flow rate of 0.8 mLlmin. The analytes were detected by electrospray ionization (ESI)-MS/MS and quantified using multiple reaction monitoring techniques in the positive ion mode. The method showed excellent linearity (r2 > 0.998) over the concentration range of 7.5 to 254 ng/mL with LOD of 2.5 ng/mL. Precision (RSD) and accuracy (recovery) were found in the ranges of 2.00 to 5.15 and 102 to 110%, respectively. The validated HPLC/ESI-MS/MS method was successfully applied to the quantification of shatavarin IV in crude, processed, and marketed (single or multiherb) AR samples. Therefore, this method could be used for QC and standardization of pharmaceutical or nutritional products containing AR.

An evaluation of the emerging vaccines against influenza in children.

BACKGROUND: Influenza is an under-appreciated cause of acute lower respiratory infections (ALRI) in children. It is estimated to cause approximately 20 million new episodes of ALRI in children annually, 97% of these occurring in developing countries. It is also estimated to result in 28000 to 112000 deaths annually in young children. Apart from hospitalisations and deaths, influenza has significant economic consequences. The current egg-based inactivated influenza vaccines have several limitations: annual vaccination, high production costs, and cannot respond adequately to meet the demand during pandemics. METHODS: We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In Stage I, we systematically reviewed the literature related to emerging cross-protective vaccines against influenza relevant to several criteria of interest: answerability; cost of development, production and implementation; efficacy and effectiveness; deliverability, affordability and sustainability; maximum potential impact on disease burden reduction; acceptability to the end users and health workers; and effect on equity. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies). They answered questions from the CHNRI framework and their "collective optimism" towards each criterion was documented on a scale from 0 to 100%. RESULTS: The experts expressed very high level of optimism for deliverability, impact on equity, and acceptability to health workers and end users. However, they expressed concerns over the criteria of answerability, low development cost, low product cost, low implementation cost, affordability and, to a lesser extent sustainability. In addition they felt that the vaccine would have higher efficacy and impact on disease burden reduction on overall influenza-associated disease rather than specifically influenza-associated pneumonia. CONCLUSION: Although the landscape of emerging influenza vaccines shows several promising candidates, it is unlikely that the advancements in the newer vaccine technologies will be able to progress through to large scale production in the near future. The combined effects of continued investments in researching new vaccines and improvements of available vaccines will hopefully shorten the time needed to the development of an effective seasonal and pandemic influenza vaccine suitable for large scale production.

An evaluation of respiratory administration of measles vaccine for prevention of acute lower respiratory infections in children.

BACKGROUND: Measles was responsible for an estimated 100,000 deaths worldwide in 2008. Despite being a vaccine-preventable disease, measles remains a major cause of morbidity and mortality in young children. Although a safe and effective injectable measles vaccine has been available for over 50 years it has not been possible to achieve the uniformly high levels of coverage (required to achieve measles eradication) in most parts of the developing world. Aerosolised measles vaccines are now under development with the hope of challenging the delivery factors currently limiting the coverage of the existing vaccine. METHODS: We used a modified CHNRI methodology for setting priorities in health research investments to assess the strengths and weaknesses of this emerging intervention to decrease the burden of childhood pneumonia. This was done in two stages. In Stage I, we systematically reviewed the literature related to emerging aerosol vaccines against measles relevant to several criteria of interest. Although there are a number of different aerosol vaccine approaches under development, for the purpose of this exercise, all were considered as one intervention. The criteria of interest were: answerability; cost of development, production and implementation; efficacy and effectiveness; deliverability, affordability and sustainability; maximum potential impact on disease burden reduction; acceptability to the end users and health workers; and effect on equity. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies). The policy makers and industry representatives accepted our invitation on the condition of anonymity, due to the sensitive nature of their involvement in such exercises. They answered questions from the CHNRI framework and their "collective optimism" towards each criterion was documented on a scale from 0 to 100%. RESULTS: The panel of experts expressed mixed feelings about an aerosol measles vaccine. The group expressed low levels of optimism regarding the criteria of likelihood of efficacy and low cost of development (scores around 50%); moderate levels of optimism regarding answerability, low cost of production, low cost of implementation and affordability (score around 60%); and high levels of optimism regarding deliverability, impact on equity and acceptability to health workers and end-users (scores over 80%). Finally, the experts felt that this intervention will have a modest but nevertheless important impact on reduction of burden of disease due to childhood pneumonia (median: 5%, interquartile range 1-15%, minimum 0%, maximum 45%). CONCLUSION: Aerosol measles vaccine is at an advanced stage of development, with evidence of good immunogenicity. This new intervention will be presented as a feasible candidate strategy in the campaign for global elimination of measles. It also presents an unique opportunity to decrease the overall burden of disease due to severe pneumonia in young children.

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.

The importance of vaccine stockpiling to respond to epidemics and remediate global supply shortages affecting immunization: strategic challenges and risks identified by manufacturers.

While stockpiling vaccines adds another layer of complexity to vaccine manufacturing, it constitutes a crucial component of comprehensive disease preparedness and control strategies in public health management. Stockpiling provides the ability to immediately respond to epidemics, disease outbreaks, vaccine shortages or stock-outs at local, regional or global levels. Some stockpiles are static, not shipped until an emergency occurs; other stockpiles are rotating with vaccines used in on-going routine immunization programmes. Programmatic use indicates which vaccines to stockpile, the nature of the stockpile and the amount of vaccine to be held at any time. For immediate shipment, fully released product must be stockpiled with the challenge of monitoring remaining shelf-life requirements and the potential risk of expiry. Existing stockpiles are managed and financed globally under the purview of international organizations in the global immunization community, except for buffer stocks held by manufacturers for short periods. The added challenges to manufacturers of stockpiling vaccines, including storage, human resources and other related costs including vaccine destruction when no longer useable, needs to be recognized. This is all the more so with the likelihood of vaccine stockpiling becoming more prominent with changing disease patterns due to climate change and population movements, as well as the significant investment in the research and development of new epidemic prevention vaccines. While vaccine stockpiles managed and financed globally provide rapid response to country requests, more attention is needed in the future to ways that vaccine stockpiling can be brought under the direct purview of individual countries or regional groupings.

Physicochemical stability and biological activity of Withania somnifera extract under real-time and accelerated storage conditions.

Stability testing at preformulation stages is a crucial part of drug development. We studied physicochemical stability and biological activity of Withania somnifera (ashwagandha) dried root aqueous extract during six months real-time and under accelerated storage conditions. The characteristic constituents of ashwagandha roots include withanolides such as withaferin A and withanolide A. We modified and validated the HPLC-DAD method for quantitative measurement of withanolides and fingerprint analysis. The results suggest a significant decline in withaferin A and withanolide A content under real and accelerated conditions. The HPLC fingerprint analysis showed significant changes in some peaks during real and accelerated storage (> 20 %). We also observed incidences of clump formation and moisture sensitivity (> 10 %) under real-time and accelerated storage conditions. These changes were concurrent with a significant decline in immunomodulatory activity (p < 0.01) during the third month of the accelerated storage. Thus, adequate control of temperature and humidity is important for WSE containing formulations. This study may help in proposing suitable guidance for storage conditions and shelf life of ashwagandha formulations.

Quantitation of novel pentavalent meningococcal polysaccharide conjugate vaccine (Men A-TT, Men C-CRM, Men Y-CRM, Men W-CRM, Men X-TT) using sandwich ELISA.

Meningococcal vaccines have been developed over the years, to control outbreaks of meningitis. There are 12 immunologically distinct serogroups of which, A, B, C, W, Y and X are predominant and invasive in nature. Meningococcal vaccines can be sorted out as, polysaccharide vaccines, polysaccharide protein conjugate vaccines or protein based (independent of polysaccharides) vaccines. Stringent quality control analysis as per the regulatory guidelines is a requirement for any vaccine manufacturer for commercial release of vaccines. Quantitation becomes challenging when it comes to analysis of multivalent vaccines. We describe the quantitation of novel pentavalent meningococcal polysaccharide conjugate vaccine manufactured at Serum Institute of India Pvt Ltd (SIIPL). Briefly, sandwich ELISA assay was developed to quantitate five different serogroups (Men A-TT, Men C-CRM, Men Y-CRM, Men W-CRM, Men X-TT) in pentavalent meningococcal polysaccharide conjugate vaccine containing two different carrier proteins (TT and CRM). ELISA reported herein showed significant reproducibility and repeatability over a range of developed standard curve with acceptable coefficient of variation (<15%) for both intra and inter assay. Furthermore analysis showed that, polysaccharide conjugate (PC) contents were within the accepted range (±30%) of the stated label claim. The immunoassay was verified for its sensitivity, accuracy and precision. Based on the relevant experimental data; it is proposed that, reported sandwich ELISA is well suited for quantitation of individual polysaccharide conjugate from pentavalent formulation. Furthermore, the ELISA was explored for forced degradation and polysaccharide spiking studies. This leads to open up an area of research for sandwich ELISA as a tool to assess the integrity of vaccine as well as for lot to lot consistency monitoring.

Emerging manufacturers engagements in the COVID -19 vaccine research, development and supply.

The World Health Organization declared the COVID-19 disease as a pandemic requiring a rapid response. Through online search, direct communication with network members and an internal survey, engagements of developing countries' vaccine manufacturers' network members in the research and development of COVID-19 vaccines and their capacities in the manufacturing, fill-finish and distribution of vaccines were assessed. Currently, 19 network members engaged in research and development of COVID-19 vaccines, using six principal technology platforms. In addition, an internal survey showed that the number of vaccines supplied collectively by 37 members, in 2018-19, was about 3.5 billion doses annually. Almost a third of network members having vaccines prequalified by the World Health Organization comply with international regulations and mechanisms to distribute vaccines across borders. The use of existing manufacturing, fill-finish and distribution capabilities can support an efficient roll-out of vaccines against COVID-19, while maintaining supply security of existing vaccines for on-going immunization programmes.

Emerging markets & emerging needs: developing countries vaccine manufacturers' perspective & its current status.

The success of vaccination has remained an important contribution towards public health in both industrialised and developing countries. However, there are still unmet public health needs in vaccine preventable diseases owing to issues related to affordability, supply, public awareness, research and development, intellectual property, skilled human resource, etc. Various global initiatives are being taken to tackle such issues. DCVMN, Developing Country Vaccine Manufacturers' Network, is one of such novel initiatives by developing countries, and is playing an important role in facilitating cheaper and quality vaccines to children of the world. DCVMN has become an international body for emerging vaccine manufacturers from the developing world. This manuscript provides an overview of DCVMN with respect to its origin, objectives, achievements, limitations and expectations.

Stability testing of vaccines: Developing Countries Vaccine Manufacturers' Network (DCVMN) perspective.

Stability testing is an integral part of the vaccine manufacturing process and is crucial for the success of immunization programs. WHO (World Health Organization) has recently published guidelines on the stability testing of vaccines. These guidelines enlist scientific basis and principles for stability testing at various stages like development, pre-clinical, clinical, licensing, lot release and post-licensure monitoring. DCVMN (Developing Countries Vaccine Manufacturers' Network) is an international body of developing countries vaccine manufacturers and has viewpoints on technical and administrative issues in stability testing of vaccines. We here highlight viewpoints, possible roles and global expectations of DCVMN in the area of stability testing of vaccines.

Immunomodulatory activity of Asparagus racemosus on systemic Th1/Th2 immunity: implications for immunoadjuvant potential.

ETHNOPHARMACOLOGICAL RELEVANCE: Roots of Asparagus racemosus Willd (Shatavari in vernacular) are widely used in Ayurveda as Rasayana for immunostimulation, galactogogue as also in treatment of conditions like ulcers and cancer. Various studies have indicated immunomodulatory properties of Shatavari root extracts and formulations. AIM OF THE STUDY: To study the effect of standardized Asparagus racemosus root aqueous extract (ARE) on systemic Th1/Th2 immunity of SRBC sensitized animals. MATERIALS AND METHODS: We used HPTLC to quantify steroidal saponins (Shatavarin IV, Immunoside) and flow cytometry to study effects of ARE on Th1/Th2 immunity. SRBC specific antibody titres and DTH responses were also monitored as markers of Th2 and Th1 responses, respectively. We also studied lymphocyte proliferation. Cyclosporin, cyclophosphamide and levamisole were used as controls. RESULTS: Treatment with ARE (100mg/(kg b.w.p.o.)) resulted in significant increase of CD3(+) and CD4/CD8(+) percentages suggesting its effect on T cell activation. ARE treated animals showed significant up-regulation of Th1 (IL-2, IFN-g) and Th2 (IL-4) cytokines suggesting its mixed Th1/Th2 adjuvant activity. Consistent to this, ARE also showed higher antibody titres and DTH responses. ARE, in combination with LPS, Con A or SRBC, produced a significant proliferation suggesting effect on activated lymphocytes. CONCLUSION: The study suggests mixed Th1/Th2 activity of ARE supports its immunoadjuvant potential.

Relationship between T-lymphocyte cytokine levels and sero-response to hepatitis B vaccines.

AIM: To investigate the cellular defects by analyzing the (Th1/Th2) cytokine levels in vaccine responders and non-responders. METHODS: Peripheral blood mononuclear cell (PBMC) from responders and non-responders were stimulated with or with out recombinant HBsAg or PHA. Broad spectrum of cytokines viz (Th1) IFN-gamma, IL-2, TNF-alpha, IL-12 and (Th2) IL-10, IL-4 were measured after in vitro stimulation with recombinant HBsAg and were compared with respective antibody titers. RESULTS: A significant decrease (P = 0.001) in Th1 and Th2 cytokines namely, IL-2, INF-gamma, TNF-alpha and IL-10 in non-responders was observed. The level of IL-4 was not significant between the three groups. Furthermore, despite a strong Th1 and Th2 cytokine response, the level of IL-12 was elevated in high-responders compared to other groups (P = 0.001) and demonstrated a positive correlation with anti-HBs titers and Th1 cytokine response. CONCLUSION: Our findings suggest that unresponsiveness to recombinant hepatitis B vaccines (rHB) is multifactorial, including specific failure of antigen presentation or the lack of both T helper Th1 and Th2 response.

Developmental strategy for a new Group A meningococcal conjugate vaccine (MenAfriVacR).

Until recently, periodic Group A meningococcal meningitis outbreaks were a major public health problem in the sub-Saharan Africa. In 2001, the Meningitis Vaccine Project (MVP), a partnership between the World Health Organization (WHO) and PATH, a Seattle-based NGO, and the Serum Institute of India Pvt Ltd (SIIPL) initiated discussions aimed at establishing a collaboration to develop a Group A meningococcal conjugate vaccine for this unmet medical need. Over the next 8 years the partnership made countless strategic decisions about product characteristics, raw materials, potential target populations, geographic prioritization and affordability of the vaccine to name a few. These decisions evolved into detailed plans for preclinical development, extensive field trials in Africa and India and a focused regulatory strategy specific for the Men A conjugate vaccine. Important characteristics of the process included, flexibility, transparency andeffective partnerships that included public agencies as well as private companies in Africa, Europe, the United States and India.

Mumps outbreaks in Canada and the United States: time for new thinking on mumps vaccines.

Mumps epidemics in Canada and the United States prompted us to review evidence for the effectiveness of 5 different vaccine strains. Early trials with the Jeryl Lynn vaccine strain demonstrated an efficacy of approximately 95%, but in epidemic conditions, the effectiveness has been as low as 62%; this is still considerably better than the effectiveness of another safe strain, Rubini (which has an effectiveness of close to 0% in epidemic conditions). The Urabe vaccine strain has an effectiveness of 54%-87% but is prone to cause aseptic meningitis. Little epidemiological information is available for other vaccines. The Leningrad-Zagreb vaccine strain, which is widely used in developing countries and costs a fraction of what vaccines cost in the developed world, seems to have encouraging results; in 1 study, the effectiveness of this vaccine exceeded 95%. Aseptic meningitis has also been reported in association with this vaccine, but the benign nature of the associated meningitis was shown recently in Croatia. Also, the Leningrad-3 strain seems to be effective but causes less-benign meningitis. No mumps vaccine equals the best vaccines in quality, but the virtually complete safety of some strains may not offset their low effectiveness. Epidemiological data are pivotal in mumps, because serological testing is subject to many interpretation problems.

Comparison of three different recombinant hepatitis B vaccines: GeneVac-B, Engerix B and Shanvac B in high risk infants born to HBsAg positive mothers in India.

AIM: To evaluate a low cost Indian recombinant hepatitis B vaccine GeneVac-B for its immunogenicity and safety in comparison to Engerix B and Shanvac B vaccine in high risk newborn infants born to hepatitis B surface antigen (HBsAg) positive mothers. METHODS: A total of 158 infants were enrolled in the study. Fifty eight infants were enrolled in the GeneVac-B group while 50 each were included for Engerix B and Shanvac B groups. A three-dose regimen of vaccination; at birth (within 24 h of birth), 1st mo and 6 mo. were adopted with 10 mug dosage administered uniformly in all the three groups. Clinical and immunological parameters were assessed for safety and immunogenicity of the vaccines, in all the enrolled infants. RESULTS: Successful follow up until seven months of age was achieved in 83% (48/58) for GeneVac-B, 76% (38/50) and 64% (32/50) for Engerix B and Shanvac B groups respectively. 100% seroconversion and seroprotection was achieved in all the three groups of infants. The geometric mean titers of anti-HBs one month after the completion of three dose of vaccination were 90.5, 80.9 and 72.5 mIU/mL in GeneVac-B, Engerix B and Shanvac B vaccine group respectively. Furthermore the level of anti-HBs increases with age of babies who were born to HBsAg positive mothers. The GMT values of anti-HBs were 226.7, 193.9 and 173.6 mIU/mL respectively in GeneVac-B, Engerix B and Shanvac B groups one year after the completion of the three doses of vaccine. No systemic reactions were reported in infants during the entire vaccination process of GeneVac-B and the other two vaccines. Clinical safety parameters remained within the normal limits throughout the study period. CONCLUSION: The study concludes that there is no significant difference between the three recombinant hepatitis B vaccines. Administration of these vaccines within 24 h of birth to babies, born to HBsAg positive mothers will reduce the incidence of HBV infection.

Omega-3-fatty acid adds to the protective effect of flax lignan concentrate in pressure overload-induced myocardial hypertrophy in rats via modulation of oxidative stress and apoptosis.

Objective of the present investigation was to study the effect of the flax lignan concentrate (FLC) and Omega-3-fatty acid (O-3-FA) on myocardial apoptosis, left ventricular (LV) contractile dysfunction and electrocardiographic abnormalities in pressure overload-induced cardiac hypertrophy. The rats were divided into five groups such as sham, aortic stenosis (AS), AS+FLC, AS+O-3-FA and AS+FLC+O-3-FA. Cardiac hypertrophy was produced in rats by abdominal aortic constriction. The rats were treated with FLC (400mg/kg, p.o.), O-3-FA (400mg/kg, p.o.) and FLC+O-3-FA orally per day for four weeks. The LV function, myocardial apoptosis, and oxidative stress were quantified. FLC+O-3-FA treatment significantly reduced hemodynamic changes, improved LV contractile dysfunction, reduced cardiomyocyte apoptosis and cellular oxidative stress. Moreover, it significantly up-regulated the VEGF expression and decreased TNF-alpha level in serum. The histological analysis also revealed that FLC+O-3-FA treatment markedly preserved the cardiac structure and inhibited interstitial fibrosis. In conclusion, FLC+O-3-FA treatment improved LV dysfunction, inhibited cardiomyocyte apoptosis, improved myocardial angiogenesis, conserved activities of membrane-bound phosphatase enzymes and suppressed inflammation through reduced oxidative stress in an additive manner than FLC alone and O-3-FA alone treatment in pressure overload-induced cardiac hypertrophy.