Neha Pant

Karolinska University Hospital, Tukholma, Stockholm, Sweden

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Publications (7)22.34 Total impact

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    ABSTRACT: Using genetically engineered lactobacilli, producing high avidity llama VHH domains (referred to as anti-rotavirus proteins; ARPs), to test the effect of multimeric antibody fragments as prophylaxis and therapy against rotavirus infection. Two ARPs, ARP1 and ARP3, shown to bind to different epitopes and act synergistically against rotavirus, were displayed on the surface of Lactobacillus paracasei as monovalent or bivalent proteins (mono- or bi-specific). Although a nonsignificant difference was observed between lactobacilli producing bispecific ARP3-ARP1 and monomeric ARPs, lactobacilli producing bispecific ARP3-ARP1 were superior at reducing the rate of diarrhea when used for prophylactic and therapeutic intervention in a mouse model of rotavirus infection in comparison to nontreated animals. Expression of bispecific antibodies in lactobacilli resulted in slight improvement of their efficacy. Furthermore, increasing the specificity would theoretically reduce the rate of appearance of viral escape mutants and would have a broader capacity to be effective against a range of viral serotypes.
    Future Microbiology 05/2011; 6(5):583-93. DOI:10.2217/fmb.11.32 · 4.28 Impact Factor
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    ABSTRACT: A series of expression cassettes which mediate secretion or surface display of antibody fragments was stably integrated in the chromosome of Lactobacillus paracasei. L. paracasei producing surface-anchored variable domain of llama heavy chain (VHH) (ARP1) directed against rotavirus showed efficient binding to rotavirus and protection in the mouse model of rotavirus infection.
    Applied and Environmental Microbiology 03/2011; 77(6):2174-9. DOI:10.1128/AEM.02690-10 · 3.67 Impact Factor
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    ABSTRACT: Rotavirus infections remain a major cause of morbidity and mortality worldwide, accounting for an estimated 600,000 deaths each year. New vaccines have been released recently but the lag time between vaccine administration and induction of an immune response can be critical in epidemic situations. A model system has been developed in which Lactobacillus, a ‘Generally Regarded As Safe’ microorganism, can be transformed with antibody fragment-encoding vectors. This allows in situ production of functional variable domains of llama heavy chain antibodies (VHH antibody fragments) against rotavirus in the intestinal tract. The modified bacteria were shown to be protective in a mouse pup model. Our approach represents a novel system for the induction of passive immunity that can be rapidly applied to populations at risk, for example through drinking water, rehydrating solutions or as a food supplement.
    Future Virology 07/2008; 3(4):327-341. DOI:10.2217/17460794.3.4.327 · 1.01 Impact Factor
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    ABSTRACT: The role of specific immunoglobulins at mucosal sites in imparting protection against disease, such as rotavirus-associated diarrhoea, is well-established. Oral immunoglobulin therapy with egg yolk-derived anti-rotavirus immunoglobulins has previously been shown to achieve moderate therapeutic effect in diarrhoea due to rotavirus in a clinical trial. Here, data on the therapeutic potential of the same immunoglobulin preparation in an infant mouse model of rotavirus-induced diarrhoea is presented. The use of an animal model has allowed therapy to be evaluated with higher doses of immunoglobulins and has suggested that an improved therapeutic effect can be achieved by increasing the dose in the clinical setting.
    Journal of Health Population and Nutrition 01/2008; 25(4):465-8. · 1.04 Impact Factor
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    ABSTRACT: Rotavirus is a worldwide cause of infectious infantile diarrhea that claims over 600,000 lives annually. Recently, two new vaccine candidates have been developed but their efficacy in developing countries, still remains to be proven. Oral delivery of specific immunoglobulins provides passive immunity and is a fast acting treatment for rotavirus diarrhea. Probiotic bacteria have also gained considerable attention lately as treatment for rotavirus diarrhea. Here we report an evaluation of the therapeutic potential of different probiotics and their combination with anti - rotavirus antibodies in a mouse model of rotavirus diarrhea. Of the six probiotic bacteria tested, Lactobacillus rhamnosus strain GG had the strongest influence in reducing prevalence, duration and severity of diarrhea and was therefore chosen for combination treatment with immunoglobulins. The combination treatment reduced the diarrhea outcome measures significantly, prevented histopathological changes and reduced the virus load in the intestines. The advantages associated with immunoglobulins and probiotics based therapy is that the treatment provides a rapid therapeutic effect and is cost efficient. These components do not require special storage conditions and could potentially complement the rehydration therapy that is currently used.
    BMC Microbiology 02/2007; 7(1):86. DOI:10.1186/1471-2180-7-86 · 2.73 Impact Factor
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    ABSTRACT: Rotavirus-induced diarrhea poses a worldwide medical problem in causing substantial morbidity and mortality among children in developing countries. We therefore developed a system for passive immunotherapy in which recombinant lactobacilli constitutively express neutralizing variable domain of llama heavy-chain (VHH) antibody fragments against rotavirus. VHH were expressed in Lactobacillus paracasei, in both secreted and cell surface-anchored forms. Electron microscopy was used to investigate the binding efficacy of VHH-expressing lactobacilli. To investigate the in vivo function of VHH-expressing lactobacilli, a mouse pup model of rotavirus infection was used. Efficient binding of the VHH antibody fragments to rotavirus was shown by enzyme-linked immunosorbent assay and scanning electron microscopy. VHH fragments expressed by lactobacilli conferred a significant reduction in infection in cell cultures. When administered orally, lactobacilli-producing surface-expressed VHH markedly shortened disease duration, severity, and viral load in a mouse model of rotavirus-induced diarrhea when administered both fresh and in a freeze-dried form. Transformed lactobacilli may form the basis of a novel form of prophylactic treatment against rotavirus infections and other diarrheal diseases.
    The Journal of Infectious Diseases 01/2007; 194(11):1580-8. DOI:10.1086/508747 · 6.00 Impact Factor
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    ABSTRACT: Apart from the use of oral rehydration solution, there are currently no treatment modalities for rotavirus induced diarrhoea, which is particularly relevant to developing countries. Fragments derived from llama heavy chain antibodies were previously shown to be highly stable, efficiently produced in yeast and exhibiting high epitope specific affinity. We now aim to demonstrate that these antibody fragments are capable of reducing morbidity of rotavirus induced diarrhoea. Here we show the isolation of rotavirus specific antibody fragments and their capability of reducing the morbidity of rotavirus induced diarrhoea in vivo in mice. They could provide a treatment modality for the moderation of human rotavirus infections having a significant impact on the course of an often fatal childhood disease.
    Vaccine 06/2006; 24(19):4130-7. DOI:10.1016/j.vaccine.2006.02.045 · 3.62 Impact Factor

Publication Stats

193 Citations
22.34 Total Impact Points

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  • 2008
    • Karolinska University Hospital
      Tukholma, Stockholm, Sweden
  • 2007
    • Karolinska Institutet
      • Department of Laboratory Medicine
      Solna, Stockholm, Sweden