Adjuvanted leptospiral vaccines: Challenges and future development of new leptospirosis vaccines

Teixeira, Aline F.; Fernandes, Luis G. V.; Cavenague, Maria F.; Takahashi, Michiaki; Santos, Jademilson Celestino dos; Passalia, Felipe José; Daroz, Brenda B.; Kochi, Leandro Toshio; Vieira, Mônica L.; Nascimento, Ana L. T. O.

doi:10.1016/j.vaccine.2019.05.087

Cited by 17 publications

(14 citation statements)

References 137 publications

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“…However, the IgG levels produced for each protein were not associated with hamster survival rate. Similar results have been observed with other leptospiral antigens when used in a challenge model (10,15). Intriguingly, Hartwig et al…”

Section: Discussionsupporting

confidence: 83%

“…In the last years, several recombinant vaccines containing outer membrane proteins, conserved among pathogenic leptospire species, which act as potential virulent factors, have been evaluated in animal challenge models (10)(11)(12)(13)(14). These vaccines have demonstrated a diverse range of protection, dependent on the adjuvant, administration route, and animal model used (15). Leptospiral immunoglobulin-like proteins, known as LigA and LigB, remain the most studied vaccine candidates among leptopiral antigens.…”

Section: Introductionmentioning

confidence: 99%

“…Leptospiral immunoglobulin-like proteins, known as LigA and LigB, remain the most studied vaccine candidates among leptopiral antigens. However, conflicting results have been reported, and some have demonstrated that these vaccines do not prevent renal colonization (10,(15)(16)(17)(18). Thus, the search for new vaccine antigens that are serovar-independent and have the ability to inhibit leptospire dissemination is still necessary.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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.

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Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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“…The availability of complete genome sequences of various pathogenic Leptospira species allowed the studies of recombinant proteins as vaccines reveling some promising antigens [14][15]. Initially, the studies focused on the most abundant outer membranes proteins, such as LipL32, OmpL1 and LipL41.…”

Section: Introductionmentioning

confidence: 99%

New strategies for Leptospira vaccine development based on LPS removal

et al. 2020

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Pathogenic spirochetes from genus Leptospira are etiologic agents of leptospirosis. Cellular vaccines against Leptospira infection often elicit mainly response against the LPS antigen of the serovars present in the formulation. There is no suitable protein candidate capable of replacing whole-cell vaccines, thus requiring new approaches on vaccine development to improve leptospirosis prevention. Our goal was to develop a whole-cell vaccine sorovarindependent based on LPS removal and conservation of protein antigens exposure, to evaluate the protective capacity of monovalent or bivalent vaccines against homologous and heterologous virulent Leptospira in hamster. Leptospire were subjected to heat inactivation, or to LPS extraction with butanol and in some cases further inactivation with formaldehyde. Hamsters were immunized and challenged with homologous or heterologous virulent serovars, blood and organs were collected from the survivors for bacterial quantification, chemokine evaluation, and analysis of sera antibody reactivity and cross-reactivity by Western blot. Immunization with either heated or low LPS vaccines with serovar Copenhageni or Canicola resulted in 100% protection of the animals challenged with homologous virulent bacteria. Notably, different from the whole-cell vaccine, the low LPS vaccines produced with serovar Canicola provided only partial protection in heterologous challenge with the virulent Copenhageni serovar. Immunization with bivalent formulation results in 100% protection of immunized animals challenged with virulent serovar Canicola. All vaccines produced were able to eliminate bacteria from the kidney of challenged animals. All the vaccines raised antibodies capable to recognize antigens of serovars not present in the vaccine formulation. Transcripts of IFNγ, CXCL16, CCL5, CXCL10, CXCR6, and CCR5, increased in all immunized animals. Conclusion: Our results showed that bivalent vaccines with reduced LPS may be an interesting strategy for protection against heterologous virulent serovars. Besides the desirable multivalent protection, the low LPS vaccines are specially promising due to the expected lower reatogenicity.

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“…Leptospirosis is a neglected infectious disease of global importance caused by pathogenic spirochetes of the genus Leptospira (NAGEL et al, 2019;TEIXEISRA et al, 2019). The disease is endemic and represents serious risks to Public Health in Brazil.…”

Section: Introductionmentioning

confidence: 99%

Epidemiological aspects of leptospirosis in cattle herds from indigenous reserves

Guedelha

Sousa

et al. 2019

AVB

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The aim of the current study is to evaluate the epidemiological aspects of leptospirosis in cattle herds from indigenous reserves. Serum samples from cows-not vaccinated against the disease and distributed in five indigenous reserves of Barra do Corda region, Maranhão State-were subjected to the microscopic agglutination technique. An epidemiological questionnaire focused on investigating the risk factors associated with Leptospira spp. infection was applied in each indigenous reserve. Of the 300 analyzed samples, 80% presented positive reactions with titers equal to or higher than 1:100. Reactive animals were identified in all (100%) indigenous reserves. The most often found serovars of the Leptospira spp. complex are herein presented in descending order:

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Adjuvanted leptospiral vaccines: Challenges and future development of new leptospirosis vaccines

Cited by 17 publications

References 137 publications

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

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

New strategies for Leptospira vaccine development based on LPS removal

Epidemiological aspects of leptospirosis in cattle herds from indigenous reserves

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