Evaluation of a Multivalent Vaccine Against Lymphatic Filariasis in Rhesus Macaque Model

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Nov 18

PMID 25401783

Citations 13

Authors

Gajalakshmi Dakshinamoorthy

Agneta von Gegerfelt

Hanne Andersen

Mark Lewis

Ramaswamy Kalyanasundaram

Affiliations

Soon will be listed here.

Abstract

Lymphatic filariasis affects 120 million people worldwide and another 1.2 billion people are at risk of acquiring the infection. Chemotherapy with mass drug administration is substantially reducing the incidence of the infection. Nevertheless, an effective vaccine is needed to prevent the infection and eradicate the disease. Previously we reported that a multivalent fusion protein vaccine (rBmHAT) composed of small heat shock proteins 12.6 (HSP12.6), abundant larval transcript-2 (ALT-2) and large extracellular domain of tetraspanin (TSP LEL) could confer >95% protection against the challenge infection with Brugia malayi infective larvae (L3) in mouse and gerbil models. In this study we evaluated the immunogenicity and efficacy of rBmHAT fusion protein vaccine in a rhesus macaque model. Our results show that rBmHAT is highly immunogenic in rhesus macaques. All the vaccinated monkeys developed significant titers of antigen-specific IgG antibodies against each of the component antigens (16,000 for rBmHSP12.6), (24,000 for rBmALT-2) and (16,000 for rBmTSP-LEL). An in vitro antibody dependent cellular cytotoxicity (ADCC) assay performed using the sera samples from vaccinated monkeys showed that the anti-rBmHAT antibodies are functional with 35% killing of B. malayi L3s. Vaccinated monkeys also had antigen responding cells in the peripheral blood. Vaccine-induced protection was determined after challenging the monkeys with 500 B. malayi L3. Following challenge infection, 3 out of 5 vaccinated macaques failed to develop the infection. These three protected macaques had high titers of IgG1 antibodies and their PBMC secreted significantly high levels of IFN-γ in response to the vaccine antigens. The two vaccinated macaques that picked the infection had slightly low titers of antibodies and their PBMC secreted high levels of IL-10. Based on these findings we conclude that the rBmHAT vaccine is highly immunogenic and safe and can confer significant protection against challenge infections in rhesus macaques.

Citing Articles

Harnessing Immune Evasion Strategy of Lymphatic Filariae: A Therapeutic Approach against Inflammatory and Infective Pathology.

Bhoj P, Togre N, Khatri V, Goswami K Vaccines (Basel). 2022; 10(8).

PMID: 36016123 PMC: 9415972. DOI: 10.3390/vaccines10081235.

Malaria transmission-blocking conjugate vaccine in ALFQ adjuvant induces durable functional immune responses in rhesus macaques.

Scaria P, Anderson C, Muratova O, Alani N, Trinh H, Nadakal S NPJ Vaccines. 2021; 6(1):148.

PMID: 34887448 PMC: 8660773. DOI: 10.1038/s41541-021-00407-3.

Highlighting the Relevance of CD8 T Cells in Filarial Infections.

Kwarteng A, Asiedu E, Koranteng K, Opoku Asiedu S Front Immunol. 2021; 12:714052.

PMID: 34603287 PMC: 8481813. DOI: 10.3389/fimmu.2021.714052.

Fecundity of adult female worms were affected when Brugia malayi infected Mongolian gerbils were immunized with a multivalent vaccine (rBmHAXT) against human lymphatic filarial parasite.

Khatri V, Chauhan N, Kalyanasundaram R Acta Trop. 2020; 208:105487.

PMID: 32437645 PMC: 7655632. DOI: 10.1016/j.actatropica.2020.105487.

Advances in Vaccine Development for Human Lymphatic Filariasis.

Kalyanasundaram R, Khatri V, Chauhan N Trends Parasitol. 2019; 36(2):195-205.

PMID: 31864894 PMC: 6986804. DOI: 10.1016/j.pt.2019.11.005.

References

Critchley J, Addiss D, Ejere H, Gamble C, Garner P, Gelband H . Albendazole for the control and elimination of lymphatic filariasis: systematic review. Trop Med Int Health. 2005; 10(9):818-25. DOI: 10.1111/j.1365-3156.2005.01458.x. View

Day K . The endemic normal in lymphatic filariasis: A static concept. Parasitol Today. 1991; 7(12):341-3. DOI: 10.1016/0169-4758(91)90215-a. View

Mishra K, Raj D, Dash A, Hazra R . Combined detection of Brugia malayi and Wuchereria bancrofti using single PCR. Acta Trop. 2005; 93(3):233-7. DOI: 10.1016/j.actatropica.2005.01.001. View

Parish C, Glidden M, Quah B, Warren H . Use of the intracellular fluorescent dye CFSE to monitor lymphocyte migration and proliferation. Curr Protoc Immunol. 2009; Chapter 4:4.9.1-4.9.13. DOI: 10.1002/0471142735.im0409s84. View

Wong M, Guest M, Lim K, Sivanandam S . Experimental Brugia malayi infections in the rhesus monkey. Southeast Asian J Trop Med Public Health. 1977; 8(2):265-73. View

Joseph S, Ramaswamy K . Single multivalent vaccination boosted by trickle larval infection confers protection against experimental lymphatic filariasis. Vaccine. 2013; 31(33):3320-6. PMC: 3713514. DOI: 10.1016/j.vaccine.2013.05.077. View

Shearer M, Dark R, Chodosh J, Kennedy R . Comparison and characterization of immunoglobulin G subclasses among primate species. Clin Diagn Lab Immunol. 1999; 6(6):953-8. PMC: 95804. DOI: 10.1128/CDLI.6.6.953-958.1999. View

Turner P, Copeman B, Gerisi D, Speare R . A comparison of the Og4C3 antigen capture ELISA, the Knott test, an IgG4 assay and clinical signs, in the diagnosis of Bancroftian filariasis. Trop Med Parasitol. 1993; 44(1):45-8. View

CRANDALL R, Crandall C, NEILSON J, Fletcher J, Kozek W, Redington B . Antibody responses to experimental Brugia malayi infections in patas and rhesus monkeys. Acta Trop. 1983; 40(1):53-64. View

10.

Maizels R, Holland M, Falcone F, Zang X, Yazdanbakhsh M . Vaccination against helminth parasites--the ultimate challenge for vaccinologists?. Immunol Rev. 1999; 171:125-47. DOI: 10.1111/j.1600-065x.1999.tb01345.x. View

11.

Jin B, Kim S, Lee J, Kang S, Han H, Jang Y . Alum Directly Modulates Murine B Lymphocytes to Produce IgG1 Isotype. Immune Netw. 2013; 13(1):10-5. PMC: 3607705. DOI: 10.4110/in.2013.13.1.10. View

12.

Veerapathran A, Dakshinamoorthy G, Gnanasekar M, Reddy M, Kalyanasundaram R . Evaluation of Wuchereria bancrofti GST as a vaccine candidate for lymphatic filariasis. PLoS Negl Trop Dis. 2009; 3(6):e457. PMC: 2685978. DOI: 10.1371/journal.pntd.0000457. View

13.

Pearlman E, Kroeze W, Hazlett Jr F, Chen S, Mawhorter S, Boom W . Brugia malayi: acquired resistance to microfilariae in BALB/c mice correlates with local Th2 responses. Exp Parasitol. 1993; 76(2):200-8. DOI: 10.1006/expr.1993.1023. View

14.

FOLSE D, Ewert A . Edema resulting from experimental filariasis. Lymphology. 1988; 21(4):244-7. View

15.

Anand S, Gnanasekar M, Thangadurai M, Prabhu P, Kaliraj P, Ramaswamy K . Immune response studies with Wuchereria bancrofti vespid allergen homologue (WbVAH) in human lymphatic filariasis. Parasitol Res. 2007; 101(4):981-8. PMC: 2763210. DOI: 10.1007/s00436-007-0571-2. View

16.

Liu J, Wang G, Chen Y, Tu Z, Fang Z . Observations on the clinical manifestations and treatment of an experimental infection with Brugia malayi in man. J Trop Med Hyg. 1989; 92(2):93-6. View

17.

Wong M, Fredericks H, Ramachandran C . Studies on immunization against Brugia malayi infection in the rhesus monkey. Bull World Health Organ. 1969; 40(4):493-501. PMC: 2556115. View

18.

Mahanty S, Luke H, Kumaraswami V, Narayanan P, Vijayshekaran V, Nutman T . Stage-specific induction of cytokines regulates the immune response in lymphatic filariasis. Exp Parasitol. 1996; 84(2):282-90. DOI: 10.1006/expr.1996.0114. View

19.

Choi Y, Ghedin E, Berriman M, McQuillan J, Holroyd N, Mayhew G . A deep sequencing approach to comparatively analyze the transcriptome of lifecycle stages of the filarial worm, Brugia malayi. PLoS Negl Trop Dis. 2011; 5(12):e1409. PMC: 3236722. DOI: 10.1371/journal.pntd.0001409. View

20.

Shedlock D, Silvestri G, Weiner D . Monkeying around with HIV vaccines: using rhesus macaques to define 'gatekeepers' for clinical trials. Nat Rev Immunol. 2009; 9(10):717-28. PMC: 4317297. DOI: 10.1038/nri2636. View