Evaluation of the immunogenicity of a recombinant glycoprotein-based Chandipura vaccine in combination with commercially available DPT vaccine
ABSTRACT Chandipura virus (CHPV) belongs to family Rhabdovoridae and has emerged as an encephalitis causing pathogen with high mortality among pediatric population from three Indian states. The recombinant glycoprotein (rGp) was shown to be an excellent vaccine candidate as evaluated in a murine model. As the disease is predominantly rural, to ensure maximum coverage for Chandipura vaccine, an attempt was made to evaluate combination of rGp and a commercially available DPT vaccine (CHP-DPT). When CHP-DPT was used for immunization of mice, 90% seroconversion against rGp with high antibody titers (1:1200 by ELISA and 1:320 by neutralization test) was observed and did not differ from mice immunized with rGp alone (P>0.05). Similarly seroconversions and antibody titers against DPT were comparable in mice immunized with DPT alone or in combination with rGp. Seroconversions and antibody titers ranged from 90 to 100% and 1:1200 to 1:2400 respectively. Intracerebral challenge with homologous CHPV strain resulted in 90% survival in rGp alone and CHP-DPT groups. Lymphocyte proliferative responses were also comparable. Thus, neither components of the candidate combination vaccine inhibited immune response to the other component. Substantial decrease of CHPV RNA and absence of histopathological changes in the brains of surviving immunized mice after challenge than the unimmunized controls further confirm efficacy of the vaccine even after intracerebral challenge. In conclusion, a combination vaccine seems feasible for use in a restricted area where the disease is endemic and should be subjected to additional studies required for future use in humans.
Article: Emerging Viral Infections in India[Show abstract] [Hide abstract]
ABSTRACT: Despite an elaborate armamentarium to tackle microbes, emerging infectious diseases remain a crucial global challenge. Emerging infections can be defined as “infections that have newly appeared in a population or have existed previously but are rapidly increasing in incidence or geographic range.” Several factors like increase in international travel and trade, human encroachment on wild-life habitats, changes in agricultural practices and wild-life trade have contributed to the emergence of pathogens. Emergence/re-emergence of several viral infections has been reported from India in the past few decades; some of the important emerging viral infections are discussed in this review. They include infection due to Nipah, Hantaviruses, Chikungunya, Human Enterovirus-71, Influenza, Chandipura, Crimean Congo, SARS Coronavirus, Buffalopox, Dengue and Japanese Encephalitis viruses. Creating increased awareness and training of clinical microbiologists/virologists for identification of new/emerging pathogens, and prompt reporting and management of outbreaks is essential to tackle the threat posed by emerging/re-emerging infections.Proceedings of the National Academy of Sciences, India - Section B: Biological Sciences 03/2012; 82(1). DOI:10.1007/s40011-011-0001-1 · 0.40 Impact Factor
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ABSTRACT: Two commercial databases (Pharmaprojects and Adis Insight R&D) were queried for antibacterial agents in clinical development. Particular attention was given to antibacterial agents for systemic administration. For each agent, reviewers were requested to indicate whether its spectrum of activity covered a set of selected multidrug-resistant bacteria, and whether it had a new mechanism of action or a new target. In addition, PubMed was searched for antibacterial agents in development that appeared in review articles. Out of 90 agents that were considered to fulfil the inclusion criteria for the analysis, 66 were new active substances. Fifteen of these could be systemically administered and were assessed as acting via a new or possibly new mechanism of action or on a new or possibly new target. Out of these, 12 agents were assessed as having documented in vitro activity against antibiotic-resistant Gram-positive bacteria and only four had documented in vitro activity against antibiotic-resistant Gram-negative bacteria. Of these four, two acted on new or possibly new targets and, crucially, none acted via new mechanisms of action. There is an urgent need to address the lack of effective treatments to meet the increasing public health burden caused by multidrug-resistant bacteria, in particular against Gram-negative bacteria.Drug resistance updates: reviews and commentaries in antimicrobial and anticancer chemotherapy 03/2011; 14(2):118-24. DOI:10.1016/j.drup.2011.02.003 · 8.82 Impact Factor
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ABSTRACT: A Vero cell based vaccine candidate against Chandipura (CHP) virus (Rhabdoviridae: Vesiculovirus), was developed and evaluated for immunogenicity in mice. Virus was purified by ultracentrifugation on 30% glycerol cushion followed by differential centrifugation on 10-60% sucrose gradient and inactivated with β-propio lactone at a concentration of 1:3500. The inactivated product was blended with aluminium phosphate (3%) and immunized 4-week-old Swiss albino mice. Neutralizing antibodies in the range of 1:10 to 160 and 1:80 to 1:320 was detected with 85% and 100% sero-conversion after 2nd and 3rd dose, respectively. All the immunized mice with antibody titer above 1:20 survived live virus challenge. The vaccine candidate has potential to be an efficient vaccine against CHP virus.Vaccine 06/2011; 29(28):4613-7. DOI:10.1016/j.vaccine.2011.04.063 · 3.49 Impact Factor