Immunization with inflammatory proteome of Brugia malayi adult worm induces a Th1/Th2-immune response and confers protection against the filarial infection

Sahoo, Malaya K.; Sisodia, Brijesh S.; Dixit, Saurabh; Joseph, Sujith; Gaur, Ritu; Verma, Shiv Kumar; Verma, Atul Kumar; Shasany, Ajit Kumar; Dowle, Adam; Murthy, P. K.

doi:10.1016/j.vaccine.2009.05.015

Cited by 36 publications

(15 citation statements)

References 66 publications

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“…In this study we show that spleen cells from vaccinated gerbils that were boosted with trickle infections predominantly secreted IL-4 in response to rBmHAT stimulation suggesting a polarized Th2 responses similar to that observed with irradiated larval vaccination (31,32). However, BmHAT DNA prime protein boost vaccination followed by trickle infection resulted in a mixed Th1/Th2 responses similar to that described previously (12).…”

Section: Discussionsupporting

confidence: 66%

“…A strong Th2 polarized responses occurred following vaccination with irradiated larvae (9,31), whereas, parasite fractions and recombinant products mainly elicited a mixed Th1/Th2 responses especially following a prime-boost approach (13,32). In this study we show that spleen cells from vaccinated gerbils that were boosted with trickle infections predominantly secreted IL-4 in response to rBmHAT stimulation suggesting a polarized Th2 responses similar to that observed with irradiated larval vaccination (31,32).…”

Section: Discussionmentioning

confidence: 99%

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Single multivalent vaccination boosted by trickle larval infection confers protection against experimental lymphatic filariasis

Joseph

Kalyanasundaram

2013

Vaccine

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The multivalent vaccine BmHAT, consisting of the Brugia malayi infective larval (L3) antigens heat shock protein12.6 (HSP12.6), abundant larval transcript-2 (ALT-2) and tetraspanin large extra cellular loop (TSP-LEL), was shown to be protective in rodent models from our laboratory. We hypothesize that since these antigens were identified using protective antibodies from immune endemic normal individuals, the multivalent vaccine can be augmented by natural L3 infections providing protection to the vaccinated host. This hypothesis was tested using single dose of DNA and Protein or Protein alone of the BmHAT vaccination in gerbils followed by live trickle L3 infection as booster dose. Vaccine-induced protection in gerbils was determined by worm establishment, micropore chamber assay and by antibody dependant cell cytotoxicity (ADCC) assay. Results were compared with the traditional prime-boost vaccination regimen. Gerbils vaccinated with BmHAT and boosted with L3 trickle infection were protected 51% (BmHAT DNA-Protein) and 48% (BmHAT Protein) respectively. BmHAT vaccination plus L3 trickle booster generated significant titer of antigen-specific IgG antibodies comparable to the traditional prime boost vaccination approach. BmHAT vaccination plus L3 trickle booster also generated antigen-specific cells in the spleen of vaccinated animals and these cells secreted predominantly IFN-γ and IL-4 in response to the vaccine antigens. These studies thus show that single dose of BmHAT multivalent vaccination followed by L3 trickle booster infection can confer significant protection against lymphatic filariasis.

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Section: Discussionsupporting

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Single multivalent vaccination boosted by trickle larval infection confers protection against experimental lymphatic filariasis

Joseph

Kalyanasundaram

2013

Vaccine

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“…Vaccine research has focused largely on the use of fractions of adult worms separated primarily by size. It has been shown that the 54-to 68-kDa fraction (fraction 6 [F6]) and the 20-to 28-kDa fraction (F14) contain vaccine candidates that may be effective at eliminating adult worms (62), although only F6 has been shown to be protective against challenge with infective larvae (62). Other promising vaccine candidates from adult antigens include BmA-2, which is a 120-kDa antigen, BmT5, which is 34 kDa, and a single epitope from thioredoxin peroxidase (48,63,64).…”

Section: Brugia Malayimentioning

confidence: 99%

A Comprehensive, Model-Based Review of Vaccine and Repeat Infection Trials for Filariasis

et al. 2013

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SUMMARY Filarial worms cause highly morbid diseases such as elephantiasis and river blindness. Since the 1940s, researchers have conducted vaccine trials in 27 different animal models of filariasis. Although no vaccine trial in a permissive model of filariasis has provided sterilizing immunity, great strides have been made toward developing vaccines that could block transmission, decrease pathological sequelae, or decrease susceptibility to infection. In this review, we have organized, to the best of our ability, all published filaria vaccine trials and reviewed them in the context of the animal models used. Additionally, we provide information on the life cycle, disease phenotype, concomitant immunity, and natural immunity during primary and secondary infections for 24 different filaria models.

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“…This reduction was seen with both male and female worms, suggesting effector mechanisms not only acting against intrauterine Mf in female worms, but against target structures of adult worms. In line with this, different developmental stages of filariae share many molecular structures [41] and cross-reactive immunization effects are documented for filarial immunizations [19], [42]. Importantly, it is unlikely that the lower worm burden observed on days 70 and 90 p.i.…”

Section: Discussionmentioning

confidence: 71%

Immunization with L. sigmodontis Microfilariae Reduces Peripheral Microfilaraemia after Challenge Infection by Inhibition of Filarial Embryogenesis

et al. 2012

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BackgroundLymphatic filariasis and onchocerciasis are two chronic diseases mediated by parasitic filarial worms causing long term disability and massive socioeconomic problems. Filariae are transmitted by blood-feeding mosquitoes that take up the first stage larvae from an infected host and deliver it after maturation into infective stage to a new host. After closure of vector control programs, disease control relies mainly on mass drug administration with drugs that are primarily effective against first stage larvae and require many years of annual/biannual administration. Therefore, there is an urgent need for alternative treatment ways, i.e. other effective drugs or vaccines.Methodology/Principal FindingsUsing the Litomosoides sigmodontis murine model of filariasis we demonstrate that immunization with microfilariae together with the adjuvant alum prevents mice from developing high microfilaraemia after challenge infection. Immunization achieved 70% to 100% protection in the peripheral blood and in the pleural space and furthermore strongly reduced the microfilarial load in mice that remained microfilaraemic. Protection was associated with the impairment of intrauterine filarial embryogenesis and with local and systemic microfilarial-specific host IgG, as well as IFN-γ secretion by host cells from the site of infection. Furthermore immunization significantly reduced adult worm burden.Conclusions/SignificanceOur results present a tool to understand the immunological basis of vaccine induced protection in order to develop a microfilariae-based vaccine that reduces adult worm burden and prevents microfilaraemia, a powerful weapon to stop transmission of filariasis.

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Immunization with inflammatory proteome of Brugia malayi adult worm induces a Th1/Th2-immune response and confers protection against the filarial infection

Cited by 36 publications

References 66 publications

Single multivalent vaccination boosted by trickle larval infection confers protection against experimental lymphatic filariasis

Single multivalent vaccination boosted by trickle larval infection confers protection against experimental lymphatic filariasis

A Comprehensive, Model-Based Review of Vaccine and Repeat Infection Trials for Filariasis

Immunization with L. sigmodontis Microfilariae Reduces Peripheral Microfilaraemia after Challenge Infection by Inhibition of Filarial Embryogenesis

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