<i>Wuchereria bancrofti</i> 20/22 a homologue of abundant larval transcript L3 stage filarial antigen: molecular and immunological characterization

Aparnaa, Ramanathan; Natarajan, M.; Harini, Asai; Jeyaprita, Parasurama Jawaharlal; Anugraha, Gandhirajan; Amdare, Nitin; Khatri, Vishal; Reddy, M. Janga; Kaliraj, Perumal

doi:10.1111/pim.12120

Cited by 6 publications

(16 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Micropore chamber method was carried out 1 week after final immunization to evaluate the immunoprophylactic efficacy of FEP, which is a widely used technique for protection study . The experiments were performed three times with five animals per group in each experiment.…”

Section: Resultsmentioning

confidence: 99%

Chimeric Epitope Vaccine from Multistage Antigens for Lymphatic Filariasis

et al. 2015

Self Cite

View full text Add to dashboard Cite

Lymphatic filariasis, a mosquito-borne parasitic disease, affects more than 120 million people worldwide. Vaccination for filariasis by targeting different stages of the parasite will be a boon to the existing MDA efforts of WHO which required repeated administration of the drug to reduce the infection level and sustained transmission. Onset of a filaria-specific immune response achieved through antigen vaccines can act synergistically with these drugs to enhance the parasite killing. Multi-epitope vaccine approach has been proved to be successful against several parasitic diseases as it overcomes the limitations associated with the whole antigen vaccines. Earlier results from our group suggested the protective efficacy of multi-epitope vaccine comprising two immunodominant epitopes from Brugia malayi antioxidant thioredoxin (TRX), several epitopes from transglutaminase (TGA) and abundant larval transcript-2 (ALT-2). In this study, the prophylactic efficacy of the filarial epitope protein (FEP), a chimera of selective epitopes identified from our earlier study, was tested in a murine model (jird) of filariasis with L3 larvae. FEP conferred a significantly (P < 0.0001) high protection (69.5%) over the control in jirds. We also observed that the multiepitope recombinant construct (FEP) induces multiple types of protective immune responses, thus ensuring the successful elimination of the parasite; this poses FEP as a potential vaccine candidate.

show abstract

Section: Resultsmentioning

confidence: 99%

Chimeric Epitope Vaccine from Multistage Antigens for Lymphatic Filariasis

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…Vaccination with a fusion protein of Bm-103 and Bm-RAL-2 or concurrently, induced a significant worm reduction of 61% and 42% in gerbils respectively (Arumugam et al, 2016). The prophylactic efficacy of Wb20/22 protein without acidic domain (WOAD) conferred 62.26% protection which was higher than 49.82% of Wb20/22 and 54.78% of Wb20/22 without signal sequence (WOSS) (Aparnaa et al, 2014). Anugraha et al reported the prophylactic efficacy of the filarial epitope protein (FEP), a chimera of selective epitopes from thioredoxin (TRX), several epitopes from transglutaminase (TGA) and abundant larval transcript-2 (ALT-2) indicating a significant protection (69.5%) against filarial L3 larvae in jirds (Anugraha et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Immunological evaluation of fusion protein of Brugia malayi abundant larval protein transcript-2 (BmALT-2) and Tuftsin in experimental mice model

Paul

Ilamaran

Khatri

et al. 2019

Parasite Epidemiology and Control

View full text Add to dashboard Cite

Introduction Filariasis, a neglected tropical helminth disease needs vaccine besides mass drug administration for its successful eradication. Methods An attempt was made to produce a fusion protein (P-TUFT-ALT-2) of abundant larval transcript protein-2 and Tuftsin to enhance its immunogenicity. The fusion construct was expressed in Pichia pastoris , a nonexpensive commercial expression system. This study focused on the evaluation of immunological response produced by P-TUFT-ALT-2 in Balb/c mice. Result and discussion P-TUFT-ALT-2 showed an enhanced IgG peak titre compared to E. coli expressed E-ALT-2 and P. pastoris expressed P-ALT-2. IgG2b, IgG2a and IgG1 production were predominant indicating a balanced Th1/Th2 response. P-TUFT-ALT-2 also induced about 28% and 9.5% higher splenocyte proliferation over control and E-ALT-2 respectively. Splenocytes produced predominant IFN-γ followed by IL-5, IL-2 and IL-10 specifying a balanced Th1/Th2 response. P-TUFT-ALT-2 showed 55% to 80% with an average of 65% cytotoxicity in B. malayi L3 larvae in in vitro ADCC assay. Conclusion This experiment validates P-TUFT-ALT-2 as a potential vaccine candidate for human lymphatic filariasis.

show abstract

“…malayi , and with higher levels of seropositivity against W . bancrofti ALT-2 in endemic normal patients relative to those who are microfilaremic or experiencing chronic pathology [ 10 , 45 , 50 ]. It is potentially consistent with reports of immunity to a 23 kDa antigen corresponding with microfilaremia relative to overt pathology in loiasis patients [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Differential Evolutionary Selection and Natural Evolvability Observed in ALT Proteins of Human Filarial Parasites

et al. 2016

View full text Add to dashboard Cite

The abundant larval transcript (ALT-2) protein is present in all members of the Filarioidea, and has been reported as a potential candidate antigen for a subunit vaccine against lymphatic filariasis. To assess the potential for vaccine escape or heterologous protection, we examined the evolutionary selection acting on ALT-2. The ratios of nonsynonymous (K(a)) to synonymous (K(s)) mutation frequencies (ω) were calculated for the alt-2 genes of the lymphatic filariasis agents Brugia malayi and Wuchereria bancrofti and the agents of river blindness and African eyeworm disease Onchocerca volvulus and Loa loa. Two distinct Bayesian models of sequence evolution showed that ALT-2 of W. bancrofti and L. loa were under significant (P<0.05; P < 0.001) diversifying selection, while ALT-2 of B. malayi and O. volvulus were under neutral to stabilizing selection. Diversifying selection as measured by ω values was notably strongest on the region of ALT-2 encoding the signal peptide of L. loa and was elevated in the variable acidic domain of L. loa and W. bancrofti. Phylogenetic analysis indicated that the ALT-2 consensus sequences formed three clades: the first consisting of B. malayi, the second consisting of W. bancrofti, and the third containing both O. volvulus and L. loa. ALT-2 selection was therefore not predictable by phylogeny or pathology, as the two species parasitizing the eye were selected differently, as were the two species parasitizing the lymphatic system. The most immunogenic regions of L. loa and W. bancrofti ALT-2 sequence as modeled by antigenicity prediction analysis did not correspond with elevated levels of diversifying selection, and were not selected differently than predicted antigenic epitopes in B. malayi and O. volvulus. Measurements of ALT-2 evolvability made by χ2 analysis between alleles that were stable (O. volvulus and B. malayi) and those that were under diversifying selection (W. bancrofti and L. loa) indicated significant (P<0.01) deviations from a normal distribution for both W. bancrofti and L. loa. The relationship between evolvability and selection in L. loa followed a second order polynomial distribution (R2 = 0.89), indicating that the two factors relate to one another in accordance with an additional unknown factor. Taken together, these findings indicate discrete evolutionary drivers acting on ALT-2 of the four organisms examined, and the described variation has implications for design of novel vaccines and diagnostic reagents. Additionally, this represents the first mathematical description of evolvability in a naturally occurring setting.

show abstract

Wuchereria bancrofti 20/22 a homologue of abundant larval transcript L3 stage filarial antigen: molecular and immunological characterization

Cited by 6 publications

References 37 publications

Chimeric Epitope Vaccine from Multistage Antigens for Lymphatic Filariasis

Chimeric Epitope Vaccine from Multistage Antigens for Lymphatic Filariasis

Immunological evaluation of fusion protein of Brugia malayi abundant larval protein transcript-2 (BmALT-2) and Tuftsin in experimental mice model

Differential Evolutionary Selection and Natural Evolvability Observed in ALT Proteins of Human Filarial Parasites

Contact Info

Product

Resources

About