Recombinant vaccines against Leptospirosis

Abstract

Leptospirosis is an important neglected infectious disease that occurs in urban environments, as well as in rural regions worldwide. Rodents, the principal reservoir hosts of pathogenic Leptospira spp., and other infected animals shed the bacteria in their urine. During occupational or even recreational activities, humans that come into direct contact with infected animals or with a contaminated environment, particularly water, are at risk of infection. Prevention of urban leptospirosis is largely dependent on sanitation measures that are often difficult to implement, especially in developing countries. Vaccination with inactivated whole-cell preparations (bacterins) has limited efficacy due to the wide antigenic variation of the pathogen. Intensive efforts towards developing improved recombinant vaccines are ongoing. During the last decade, many reports on the evaluation of recombinant vaccines have been published. Partial success has been obtained with some surface-exposed protein antigens. The combination of protective antigens and new adjuvants or delivery systems may result in the much-needed effective vaccine.

Protection against Lethal Leptospirosis after Vaccination with LipL32 Coupled or Coadministered with the B Subunit of Escherichia coli Heat-Labile Enterotoxin

“…At present, the highest level of protection afforded by a recombinant vaccine was observed with the recombinant leptospiral immunoglobulin-like protein LigA from L. interrogans (10,32). However, even after six full genome sequences, molecular studies of multiple strains (1,25), and several vaccine trials (5, 11, 12) have been reported, LipL32 remains the most promising recombinant vaccine candidate.…”

“…Efforts to develop recombinant vaccines against leptospirosis have focused on outer membrane proteins (OMPs) (10). The most abundant protein in the entire leptospiral proteome is an outer membrane lipoprotein of 32 kDa, LipL32 (27), accounting for 75% of the outer membrane proteome (7).…”

Infection with Leptospira kirschneri Serovar Mozdok: First Report from the Southern Hemisphere

“…The imprint technique 14 confirmed the presence of leptospires in the kidneys, liver, and lungs of infected animals. The presence of putative virulence factors LigA and LigB, as well as LipL32 15 was confirmed by means of indirect immunofluorescence using rabbit polyclonal sera against each antigen conjugated with fluorescein isothiocyanate (excited at 450 nm). Leptospiral DNA was stained with Hoechst 33258 (Sigma-Aldrich, St. Louis, MO; excited at 350 nm).…”

“…The current vaccines, however, are heatkilled whole cells of Leptospira spp., which provide only serovar-specific protection, and only a few countries permit their use. 15 This type of vaccine could be effective in urban areas such as Salvador and São Paulo, where a single serovar is responsible for the majority of human and animal cases 3 ; however, in mixed urban/rural areas such as Pelotas, where leptospirosis is caused by several serovars, [17][18][19][20] novel vaccines capable of inducing a cross-protective response are a necessity. Therefore, characterization of clinical isolates to the serovar level is of crucial importance, not only to understand the epizootiology of the disease but also for the development of novel vaccines and diagnostic tests.…”

A Prime-Boost Strategy Using the Novel Vaccine Candidate, LemA, Protects Hamsters against Leptospirosis

“…Currently available vaccines are based on inactivated whole bacteria or membrane preparations from pathogenic leptospires that require annual booster immunizations and do not confer cross-protective immunity (8). There are more than 270 pathogenic serovars of Leptospira spp., and this antigenic diversity has been attributed to the distribution and composition of the lipopolysaccharides (LPS) in the outer membrane (OM) (9), thereby precluding their use in multivalent vaccine preparations.…”