A live attenuated-vaccine model confers cross-protective immunity against different species of the Leptospira genus

Wunder, Elsio A.; Adhikarla, Haritha; Hamond, Camila; Bonner, Katharine A Owers; Liang, Li; Rodrigues, Camila B.; Bisht, Vimla; Nally, Jarlath E.; Alt, David P.; Reis, Mitermayer Galvão dos; Diggle, Peter J.; Felgner, Philip L.; Ko, Albert I.

doi:10.7554/elife.64166

Cited by 26 publications

(31 citation statements)

References 53 publications

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“…Cross-reactivity experiments showed that infection with the Fiocruz strain triggered crossreactive antibodies against both Manilae L495 and Icterohaemorrhagiae Verdun strains. This is in line with the recent study showing that the attenuated live Fiocruz fcpA mutant confers cross-protection against infection with other serovars, including Manilae [49]. Here, we show that the Fiocruz strain triggers high amounts of IgG1 and IgG3, which by large recognize proteins.…”

Section: Plos Neglected Tropical Diseasessupporting

confidence: 93%

“…Humoral immunity against Leptospira following infection is mainly described as LPS-dependent and consequently as serovar-specific. However, cross-reactions against related serovars have been reported [49,60]. We assessed the cross-reactivity of anti-Leptospira immunoglobulins obtained after pre-infection with the virulent strain of three distinct serovars against the two other serovars'antigens.…”

Section: Cross-reactive Anti-leptospira Immunoglobulins In Sera Of Prmentioning

confidence: 99%

“…Another attenuated Copenhageni mutant, fcpA, is a motility-deficient mutant lacking the expression of a flagellar protein, FcpA [48]. Both have been used as cross-protective vaccines [44,49]. Single infection with either mutant protected mice and hamsters against homologous and heterologous challenges and reduced renal colonization [44,49].…”

Section: Introductionmentioning

confidence: 99%

“…Both have been used as cross-protective vaccines [44,49]. Single infection with either mutant protected mice and hamsters against homologous and heterologous challenges and reduced renal colonization [44,49]. Interestingly, it has been recently shown that the attenuated fcp1/ fcpA mutant conferred cross-protection through anti-Leptospira antibodies directed agains proteins, but not through agglutinating antibodies.…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, it has been recently shown that the attenuated fcp1/ fcpA mutant conferred cross-protection through anti-Leptospira antibodies directed agains proteins, but not through agglutinating antibodies. However, the isotypic nature of the immunoglobulins has not been investigated [49].…”

Section: Introductionmentioning

confidence: 99%

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Anti-Leptospira immunoglobulin profiling in mice reveals strain specific IgG and persistent IgM responses associated with virulence and renal colonization

et al. 2021

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Leptospira interrogans is a pathogenic spirochete responsible for leptospirosis, a neglected, zoonotic reemerging disease. Humans are sensitive hosts and may develop severe disease. Some animal species, such as rats and mice can become asymptomatic renal carriers. More than 350 leptospiral serovars have been identified, classified on the basis of the antibody response directed against the lipopolysaccharide (LPS). Similarly to whole inactivated bacteria used as human vaccines, this response is believed to confer only short-term, serogroup-specific protection. The immune response of hosts against leptospires has not been thoroughly studied, which complicates the testing of vaccine candidates. In this work, we studied the immunoglobulin (Ig) profiles in mice infected with L. interrogans over time to determine whether this humoral response confers long-term protection after homologous challenge six months post-infection. Groups of mice were injected intraperitoneally with 2×107 leptospires of one of three pathogenic serovars (Manilae, Copenhageni or Icterohaemorrhagiae), attenuated mutants or heat-killed bacteria. Leptospira-specific immunoglobulin (IgA, IgM, IgG and 4 subclasses) produced in the first weeks up to 6 months post-infection were measured by ELISA. Strikingly, we found sustained high levels of IgM in mice infected with the pathogenic Manilae and Copenhageni strains, both colonizing the kidney. In contrast, the Icterohaemorrhagiae strain did not lead to kidney colonization, even at high dose, and triggered a classical IgM response that peaked at day 8 post-infection and disappeared. The virulent Manilae and Copenhageni serovars elicited high levels and similar profiles of IgG subclasses in contrast to Icterohaemorrhagiae strains that stimulated weaker antibody responses. Inactivated heat-killed Manilae strains elicited very low responses. However, all mice pre-injected with leptospires challenged with high doses of homologous bacteria did not develop acute leptospirosis, and all antibody responses were boosted after challenge. Furthermore, we showed that 2 months post challenge, mice pre-infected with the attenuated M895 Manilae LPS mutant or heat-killed bacterin were completely protected against renal colonization. In conclusion, we observed a sustained IgM response potentially associated with chronic leptospiral renal infection. We also demonstrated in mice different profiles of protective and cross-reactive antibodies after L. interrogans infection, depending on the serovar and virulence of strains.

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Section: Plos Neglected Tropical Diseasessupporting

confidence: 93%

Section: Cross-reactive Anti-leptospira Immunoglobulins In Sera Of Prmentioning

confidence: 99%