Antigenic potential of a recombinant polyvalent DNA vaccine against pathogenic leptospiral infection

Abstract

Leptospirosis is a serious epidemic disease caused by pathogenic Leptospira species. The disease is endemic in most tropical and sub-tropical regions of the world. Currently, there is no effective polyvalent vaccine for prevention against most of the circulating serovars. Moreover, development of an efficient leptospiral vaccine capable of stimulating cross-protective immune responses against a wide range of serovars remains a daunting challenge. This, in part, is associated with the extensive diversity and variation of leptospiral serovars from region to region. In this study, a multi-epitope DNA vaccine encoding highly immunogenic epitopes from LipL32 and LipL41 was designed using in-silico approach. The DNA encoding antigenic epitopes was constructed from conserved pathogenic Leptospira genes (LipL32 and LipL41). Immunization of golden Syrian hamsters with the multi-epitope chimeric DNA vaccine resulted in the production of both agglutinating and neutralizing antibodies as evidence by MAT and in-vitro growth inhibition tests respectively. The antibodies produced reacted against eight different serovars and significantly reduced renal colonization following in vivo challenge. The vaccine was also able to significantly reduce renal colonization which is a very important factor responsible for persistence of leptospires among susceptible and reservoir animal hosts. In conclusion, the leptospiral multi-epitope chimeric DNA vaccine can serve as a potentially effective and safe vaccine against infection with different pathogenic leptospiral serovars.

Revisiting the Development of Vaccines Against Pathogenic Leptospira: Innovative Approaches, Present Challenges, and Future Perspectives

“…This multi-epitope DNA vaccine, administered in hamsters as a plasmid DNA vaccine, showed partial protection against lethal leptospires, induced both agglutinating and neutralizing antibodies, as confirmed by MAT and in vitro growth inhibition assays, and was capable of reducing renal colonization. Renal histopathological lesions were further analyzed and mild to moderate pathologies were found, in contrast to severe lesions observed in the control group ( 77 ). The immunogenic multi-epitope DNA vaccines represent an interesting approach, as epitopes from several immunogenic leptospiral proteins could be tested to develop a novel vaccine against leptospirosis.…”

Clinical Diagnosis of Leptospirosis in Malaysia: Challenges and Prospects

“…When Leptospires invade the human body, the immune system comprising of an innate arm responds immediately while an adaptive component develops much later (Garba et al, 2018). Immunity against Leptospira infection is thought to be humoral based.…”

“…The first human case of severe leptospirosis in Malaysia was diagnosed in 1927 (El Jalii and Bahaman, 2004). In recent years, an increase in the incidence of human leptospirosis in Malaysia has been observed to coincide with severe flooding in some major states, including Kelantan and Selangor (Garba et al, 2018). Similarly, over 18 antigenically distinct serovars have been identified among humans and animals in Malaysia based on the gold standard microscopic agglutination tests (Daud et al, 2018;Rahman et al, 2018).…”

Designing a Recombinant Multi-epitope DNA Vaccine as Candidate for Protection against Pathogenic Leptospira Infection in Animals

“…Currently available vaccines for both medical and veterinary applications, which are predominantly whole-cell killed bacterins, can not protect against serovars not included in the vaccine preparations (Bashiru and Bahaman, 2018). Also, experimental evaluations have shown that Leptospiral vaccines can effectively prevent disease and reduce shedding after challenges with the serovar included in the vaccine (Lin et al, 2016;Garba et al, 2018b). However, there is a lack of cross-reactivity among antigenically distinct serovars, which further limits the ability of available vaccines to provide heterologous protection (Branger et al, 2005;Garba et al, 2018b).…”