Immunoprotective Activity Induced by Leptospiral Outer Membrane Proteins in Hamster Model of Acute Leptospirosis

Abstract

Leptospirosis is a zoonotic disease of worldwide distribution, affecting both humans and animals. The development of an effective vaccine against leptospirosis has long been pursued but without success. Humans are contaminated after direct contact with the urine of infected animals or indirectly by contaminated water or soil. The vaccines available consist of inactivated whole-bacterial cells, and the active immunoprotective antigen is the lipopolysaccharide moiety, which is also the basis for serovar classification. However, these vaccines are short-lasting, and protection is only against serovars contained in the preparation. The search for prevalent antigens, present in pathogenic species of Leptospira, represents the most cost-effective strategy for prevention of leptospirosis. Thus, the identification of these antigens is a priority. In this study, we examined the immunoprotective effect of eight leptospiral recombinant proteins using hamster as the challenge model. Animals received subcutaneously two doses of vaccine containing 50 mg of each recombinant protein adsorbed on alum adjuvant. Two weeks after the booster, animals were challenged with virulent leptospires and monitored for 21 days. All proteins were able to induce a specific immune response, although significant protective effects on survival rate were observed only for the proteins Lsa14, rLIC13259, and rLIC11711. Of these, only rLIC13259 and rLIC11711 were found to be highly prospective in promoting renal clearance. The sterilizing potential of both proteins will be further investigated to elucidate the immunoprotective mechanisms involved in leptospirosis control. These are the first proteins involved with human complement components with the capacity to protect against virulent challenge and to eliminate the bacteria from the host.

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

“…The lack of cross-reactivity among pathogenic serovars of Leptispira causing human and animal leptospirosis has greatly hampered the successful clinical application of many experimental vaccines developed (Barazzone et al, 2022). The results of the present study show promise that this lack of cross-protective immunity can be overcome using recombinant polyvalent epitope-based vaccines, which have been previously reported by other authors (Lauretti-Ferreira et al, 2020;Teixeira et al, 2020).…”

Vaccination With Leptospira interrogans PF07598 Gene Family-Encoded Virulence Modifying Proteins Protects Mice From Severe Leptospirosis and Reduces Bacterial Load in the Liver and Kidney

“…Various inactivated whole bacterial cell-based vaccines (bacterins) are serovar-specific and limited to animal use, where this legacy technology remains incompletely effective. Subunit vaccines, and more recently a spontaneously-arising attenuation mutant of L. interrogans serovar Copenhageni (Wunder et al, 2021) have been proposed amidst the search for pan-leptospirosis vaccine candidates (Govindan et al 2021.;Haake et al, 1999;Coutinho et al, 2011;Conrad et al, 2017;Techawiwattanaboon et al, 2019;Haake and Matsunaga, 2020;Teixeira et al, 2020;Phoka et al, 2021;Rodrigues de Oliveira et al, 2021). Bacterins are limited from wider use because of adverse effects and suboptimal efficacy, including the lack of durable protective and sterilizing immunity (Levett, 2001;Techawiwattanaboon et al, 2019;Felix et al, 2020;Zaugg and Ottiger, 2021).…”

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

“…A high production of IgG was demonstrated in hamsters immunized with all eight antigens, and antibody induction was higher after the first booster, with a partial survival rate of 25 to 42% being observed. In that study, although there was a reduced survival percentage with rLIC11711 and rLIC13259, some bacterial renal clearance was seen, suggesting that both proteins merit further investigation ( 30 ).…”