Leishmania donovani whole cell antigen delivered with adjuvants protects against visceral leishmaniasis in vervet monkeys (Chlorocebus aethiops)

Mutiso, Joshua M.; Macharia, John; Taracha, Evans; Gicheru, Michael M.

doi:10.1016/s1674-8301(12)60002-5

Cited by 21 publications

(24 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Two weeks following the last day of treatment, all infected mice were sacrificed and parasite numbers were determined microscopically by counting the number of amastigotes in Giemsa stained splenic impression smears. Amastigote burdens were compared for both experimental and control groups and results expressed as the number of amastigotes per 500 splenic cell nuclei as described before [12] .…”

Section: Methodsmentioning

confidence: 99%

In vitro activity and in vivo efficacy of a combination therapy of diminazene and chloroquine against murine visceral leishmaniasis

et al. 2015

View full text Add to dashboard Cite

The present study evaluated the in vitro activity and in vivo efficacy of diminazene combined with chloroquine as a potential drug against Leishmania donovani. Amphotericin B was used as a positive control drug. In vitro activity involved incubation of various drug concentrations with promastigotes or vero cells in culture before determination of parasite growth inhibition or cell death while in vivo evaluations involved infection of various mice groups with virulent L. donovani parasites and treatment with test drug compounds following disease establishment. Weight changes in experimental mice were also evaluated before infection and throughout the experiment. The results indicated that the diminazene–chloroquine combination was at least nine times more efficacious than individual drugs in killing promastigotes in culture. The diminazene–chloroquine combination was safer (Ld50 = 0.03±0.04) than Amphotericin B (Ld50 = 0.02±0.01). Body weight in infected mice increased significantly (P = 0.0007) from day 7 to day 37 following infection (P = 0.026). However, body weight remained comparable in all mice groups during treatment (P = 0.16). The diminazene–chloroquine combination significantly reduced splenic parasite numbers as compared to individual drug therapies (P = 0.0001) although Amphotericin B was still more efficacious than any other treatment (P = 0.0001). Amongst the test compounds, the diminazene–chloroquine combination showed the lowest level of IgG antibody responses with results indicating significant negative correlation between antileishmanial antibody responses and protection against disease. These findings demonstrate the positive advantage and the potential use of a combined therapy of diminazene–chloroquine over the constituent drugs. Further evaluation is recommended to determine the most efficacious combination ratio of the two compounds.

show abstract

Section: Methodsmentioning

confidence: 99%

In vitro activity and in vivo efficacy of a combination therapy of diminazene and chloroquine against murine visceral leishmaniasis

et al. 2015

View full text Add to dashboard Cite

show abstract

“…However, the study indicated adverse reactions following immunization with BCG vaccine. More recently, these murine data were evaluated in the vervet monkey model of visceral L. donovani leishmaniasis, where animals were vaccinated with L. donovani whole sonicate antigen with or without alum-BCG, monophosphoryl lipid A or MISA 720[55]. The results indicated strong type 1 immune responses in animal groups immunized with either alum-BCG+Ag or MISA+Ag, with the MISA+Ag vaccinated animals having better results than the alum-BCG+Ag group.…”

Section: Development Of Leishmania Vaccinesmentioning

confidence: 99%

Development of Leishmania vaccines: predicting the future from past and present experience

Mutiso¹,

Macharia²,

Kiio³

et al. 2013

J Biomed Res

View full text Add to dashboard Cite

Leishmaniasis is a disease that ranges in severity from skin lesions to serious disfigurement and fatal systemic infection. Resistance to infection is associated with a T-helper-1 immune response that activates macrophages to kill the intracellular parasite in a nitric oxide-dependent manner. Conversely, disease progression is generally associated with a T-helper-2 response that activates humoral immunity. Current control is based on chemotherapeutic treatments which are expensive, toxic and associated with high relapse and resistance rates. Vaccination remains the best hope for control of all forms of the disease, and the development of a safe, effective and affordable antileishmanial vaccine is a critical global public-health priority. Extensive evidence from studies in animal models indicates that solid protection can be achieved by immunization with defined subunit vaccines or live-attenuated strains of Leishmania. However, to date, no vaccine is available despite substantial efforts by many laboratories. Major impediments in Leishmania vaccine development include: lack of adequate funding from national and international agencies, problems related to the translation of data from animal models to human disease, and the transition from the laboratory to the field. Furthermore, a thorough understanding of protective immune responses and generation and maintenance of the immunological memory, an important but least-studied aspect of antiparasitic vaccine development, during Leishmania infection is needed. This review focuses on the progress of the search for an effective vaccine against human and canine leishmaniasis.

show abstract

“…Each vaccine formulation was prepared by mixing 0.1 mg of the purified recombinant protein and Montanide ISA 720 VG in 7:3 proportion [18,19]. The mixtures were vortexed for 1 min and incubated at 4°C for 24 h. The vaccine formulations (0.1 ml) were inoculated on Luria agar plates and incubated at 37°C for 24 h to verify their sterility.…”

Section: Preparation Of the Vaccine Formulations And Immunizationmentioning

confidence: 99%

Immune responses elicited by the recombinant Erp, HspR, LppX, MmaA4, and OmpA proteins from Mycobacterium tuberculosis in mice

Okay

Çetin

Karabulut

et al. 2018

AMicr

View full text Add to dashboard Cite

Immunogenic potency of the recombinant Erp, HspR, LppX, MmaA4, and OmpA proteins from Mycobacterium tuberculosis (MTB), formulated with Montanide ISA 720 VG adjuvant, was evaluated in BALB/c mice for the first time in this study. The five vaccine formulations, adjuvant, and BCG vaccine were subcutaneously injected into mice, and the sera were collected at days 0, 15, 30, 41, and 66. The humoral and cellular immune responses against vaccine formulations were determined by measuring serum IgG and serum interferon-gamma (IFN-γ) and interleukin-12 (IL-12) levels, respectively. All formulations significantly increased IgG levels post-vaccination. The highest increase in IFN-γ level was provided by MmaA4 formulation. The Erp, HspR, and LppX formulations were as effective as BCG in enhancement of IFN-γ level. The most efficient vaccine boosting the IL-12 level was HspR formulation, especially at day 66. Erp formulation also increased the IL-12 level more than BCG at days 15 and 30. The IL-12 level boosted by MmaA4 formulation was found to be similar to that by BCG. OmpA formulation was inefficient in enhancement of cellular immune responses. This study showed that MmaA4, HspR, and Erp proteins from MTB are successful in eliciting both humoral and cellular immune responses in mice.

show abstract

Leishmania donovani whole cell antigen delivered with adjuvants protects against visceral leishmaniasis in vervet monkeys (Chlorocebus aethiops)

Cited by 21 publications

References 48 publications

In vitro activity and in vivo efficacy of a combination therapy of diminazene and chloroquine against murine visceral leishmaniasis

In vitro activity and in vivo efficacy of a combination therapy of diminazene and chloroquine against murine visceral leishmaniasis

Development of Leishmania vaccines: predicting the future from past and present experience

Immune responses elicited by the recombinant Erp, HspR, LppX, MmaA4, and OmpA proteins from Mycobacterium tuberculosis in mice

Contact Info

Product

Resources

About