Indian Journal of Medical Microbiology IAMM  | About us |  Subscription |  e-Alerts  | Feedback |  Login   
  Print this page Email this page   Small font sizeDefault font sizeIncrease font size
 Home | Ahead of Print | Current Issue | Archives | Search | Instructions  
Users Online: 65 Official Publication of Indian Association of Medical Microbiologists 
  Search
 
 ~ Next article
 ~ Previous article 
 ~ Table of Contents
  
 ~  Similar in PUBMED
 ~  Search Pubmed for
 ~  Search in Google Scholar for
 ~  Article in PDF (127 KB)
 ~  Citation Manager
 ~  Access Statistics
 ~  Reader Comments
 ~  Email Alert *
 ~  Add to My List *
* Registration required (free)  

 
 ~  Acellular Vaccines
 ~  DNA Vaccines
 ~  References
 ~  Article Tables

 Article Access Statistics
    Viewed11546    
    Printed237    
    Emailed9    
    PDF Downloaded939    
    Comments [Add]    
    Cited by others 7    

Recommend this journal

 


 
SUPPLEMENT
Year : 2006  |  Volume : 24  |  Issue : 4  |  Page : 331-336
 

Prospects of developing leptospiral vaccines for animals


Division of Bacteriology and Mycology, IVRI, Izatnagar, Bareilly - 243122, India

Correspondence Address:
S K Srivastava
Division of Bacteriology and Mycology, IVRI, Izatnagar, Bareilly - 243122
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0255-0857.29412

Rights and Permissions



How to cite this article:
Srivastava S K. Prospects of developing leptospiral vaccines for animals. Indian J Med Microbiol 2006;24:331-6

How to cite this URL:
Srivastava S K. Prospects of developing leptospiral vaccines for animals. Indian J Med Microbiol [serial online] 2006 [cited 2019 Aug 22];24:331-6. Available from: http://www.ijmm.org/text.asp?2006/24/4/331/29412


Leptospirosis is a common disease of livestock, pet animals and wildlife throughout the world. Sporadic cases and outbreaks of the disease have been reported from USA, U.K, Australia, New Zealand, USSR and countries of Europe and Asia. The disease is common in cattle, buffalo, sheep, goat, dogs and equines and causes fever, jaundice, nephritis, reproductive disorders and death. In dairy animals, loss of milk and mastitis may be observed.

In India, Taylor and Goyale for the first time in 1931 reported the isolation of Leptospira organisms from patients showing jaundice in Andaman Islands. Soon after this report, Ayyar[1] reported isolation of Leptospira. interrogans serovar Icterohaemorrhagiae from dogs in Madras city. Since then several reports have emerged confirming the prevalence of leptospirosis in various animal species and man in India.[2],[3],[4],[5] Isolation of Leptospira serovars from diseased and carrier animals including cases of leptospirosis are commonly reported from coastal regions of Kerala, Tamil Nadu, Gujarat, Maharashtra and Andaman Islands. Adinarayanan et al reported natural outbreaks of bovine leptospirosis in U.P. due to serogroup Hebdomadis.[2] Antibodies against serovars Pomona, Autumnalis, Grippotyphosa, Javanica and Poi have been reported from Tamil Nadu.[6]

Srivastava et al[7] detected agglutinins in 7% of 1839 cattle and 14.3% of 393 buffaloes belonging to various states. Agglutinins were most common against Pomona, Patoc, Icterohaemorrhagiae and Grippotyphosa. Ratnam et al[8] reported antibodies to Sejroe, Autumnalis and Pomona in cattle in Tamil Nadu. Srivastava and Kumar[9] reported seropositivity in 15.8% of 2601 cattle sera, mostly belonging to Andhra Pradesh.

Long-term control strategies of the disease include adoption of hygienic measures, rodent control and vaccinations. Commercial Leptospira vaccines are available in many countries for cattle, dogs and swine but vaccination may prove only partially effective due to generation of serovar specific immunity, prevalence of several Leptospira serovars and the tendency of the vaccinated animals to become carriers of the organisms. A successful vaccination programme requires that epidemiological studies should be continued to assess the extent of the problem and the knowledge of involvement of different Leptospira serovars in causing the disease in a given population. If in a particular region, leptospirosis is considered economically a priority disease, which has to be tackled by vaccination, the target animal population must be specified, as it may not be possible to vaccinate all the animals. In this review various attempts made in the past and the efforts being made presently on the development of Leptospira vaccines are given.

Inactivated whole culture vaccine

Over the past 50 years, a number of Leptospira vaccines have been developed and evaluated in laboratory animals, cattle, swine, dogs, sheep and horses. Most of these have been bacterins containing inactivated organisms by various chemical means and heat. Broom[10] demonstrated some protection of hamsters against Canicola given phenol-inactivated cultures in high doses. Brunner and Meyer[11] reported the successful immunization of hamsters and dogs with lyophilized Canicola or Icterohaemorrhagiae bacterin and showed the serovar specificity of their vaccines as no cross-protection was provided against other serovars. Thus, multivalent vaccines have been prepared incorporating several serovars (Copenhageni, Pomona, Hardjo, Grippotyphosa, Autumnalis and Icterohaemorrhagiae) and satisfactory results have been obtained in guinea pigs and hamsters.[12],[13]

Brown et al[14] reported the development of formalin-inactivated, adjuvant containing bacterin. Calves vaccinated with this preparation developed significant agglutination titres, whereas previous bacterins without adjuvant had generated lower titers. In addition, the vaccinated calves successfully resisted challenge with Leptospira infected guinea pig blood. Hoag and Bell[15] developed an acetic acid heat extracted Pomona bacterin, which rendered vaccinated calves resistant to leptospiremia, leptospiruria and kidney lesions. Bolin et al[16] demonstrated that steers given two of pentavalent vaccines containing serovar Hardjo bovis or Hardjoprajitno, failed to protect against the challenge infection as demonstrated by the shedding of organisms in urine though their MAT titres were higher. The study suggested that the efficacy of a vaccine should not be based on serology alone.

Palit et al[17] reported that a trivalent bovine leptospirosis vaccine against Pomona, Copenhageni and Hardjo was immunogenic and capable of inducing high titres. However, the efficacy of the vaccine remained doubtful as no challenge studies were conducted. Dhaliwal et al[18] on the other hand reported that the efficacy of a vaccine could best be measured by observing fertility performance and milk yield.

Leptospiral bacterins, when introduced into domesticated species, often failed to induce significant levels of agglutinating antibodies, especially in swine in spite of the use of adjuvant.[19] Hodges et al[20] described the use of a commercial bivalent (Pomona, Hardjo) vaccine in New Zealand, which protected pigs against the infection and prevented leptospiruria as well. Francois et al[21] demonstrated that a single vaccination of swine with a killed leptospirosis vaccine did not induce MAT titres in 96% of animals after 15 days. After 28 days the titres were 1:100 when a booster was given on day 15-post vaccination. These failures led scientists toward evaluating the type of immunoglobulins produced in response to antigenic stimulation, as animals were often refractory to infection in the absence of an agglutinating titer.[22] Currently a polyvalent anti-leptospiral vaccine called Suileptovac TPCI is available for vaccinating swine. This vaccine contains serovars Tarassovi, Canicola, Pomona and Icterohaemorrhagiae. Multivalent vaccines are useful in covering infections caused by a variety of serovars, however, the efficacy of such vaccines against diseases caused by all the serovars incorporated in the vaccine is doubtful. There are a few reports, which have demonstrated that the vaccinated animals may not develop antibody titres against all the serovars incorporated in the vaccine.[23]

Bramel and Scheidy[24] evaluated the effect of re-vaccination on horses and calves with a Pomona bacterin. Results in horses indicated a local swelling at the injection site that persisted for three to four days. One vaccination had no adverse reaction on the horse.

Bivalent bacterins for dogs that contain Canicola and Icterohaemorrhagiae have been in the market since the 1950s.[25] They are prepared from chemically inactivated whole cells, which make them relatively allergenic. Because immunity after vaccination is highly serovar specific, immunized dogs are not protected against other serovars that are common in many areas and that may infect dogs. They may also suppress the immune response in young puppies and thus vaccination of pups less than 9 or 10 weeks of age is not recommended. In addition, the vaccine-induced immunity in dogs is often less than six months; repeated vaccination in endemic areas would thus be essential for protection.[26]

In recent years, vaccines against canine leptospirosis in USA have been prepared using immunogenic subunits from most commonly disease causing serovars, Grippotyphosa and Pomona. This is used in addition to the conventional vaccine using Canicola and Icterohaemorrhagiae. The vaccine induces MAT titres not only against Pomona and Grippotyphosa but also against Autumnalis, leading to misdiagnosis of the disease caused by serovar Autumnalis.[27]

Live attenuated vaccine

One of the first attenuated live vaccines used in cattle was a Pomona vaccine.[28] The leptospires were attenuated by passage through eggs and the vaccine was used in an aborting cattle herd. Results from this field study indicated that both, live and attenuated vaccines protected cattle and reduced the abortion rate.

Hubert and Miller[29] developed a live attenuated vaccine containing gamma irradiated Icterohaemorrhagiae cells (less than 70,000 rad). Guinea pigs vaccinated with the irradiated leptospires were capable of producing agglutinating antibodies and showed protection from death and renal infection. Control animals and those receiving formalin-killed, sonically disrupted and acid-heat-extracted water-soluble bacterins, failed to provide adequate protection from clinical disease. Contradicting results were reported by Babudieri et al[30] that irradiated vaccines were no more effective in preventing either death or persistent renal infection than chemically inactivated vaccine. In both studies, the vaccines were serovar-specific.

Stalheim[31] either irradiated or exposed serovar Pomona to 60 mg/ ml dihydrostreptomycin and carried out vaccination-challenge studies in hamsters and swine. Protection was seen in both groups of animals. However, when vaccinated hamsters were challenged with a non-lethal Pomona serovar, which was capable of establishing renal infection, only 60% (6 of 10) were protected from renal infection. Leptospires could not be detected in the kidneys of challenged pigs given the experimental vaccines 14 days previously.

In the early 1970s, Fish and Kingscote[32] immunized swine with a live avirulent Pomona vaccine. Upon challenge, only control pigs were infected. Sentinel pigs did not have demonstrable agglutinins whereas the vaccinated pigs had low transient titers. Sera from vaccinated pigs with no titer were capable of passively protecting guinea pigs. Even though the attenuated live vaccines were capable of stimulating higher titers than chemically inactivated leptospiral bacterins, they have not gained wide acceptance or use among veterinary biologic manufacturers. This is probably due to the difficulty of maintaining the viability upon storage as well as the possible reversion to the virulent state in the host animal.


 ~ Acellular Vaccines Top


From killed bacterins, the focus of Leptospira vaccine research shifted towards defining the primary structural component responsible for protection upon challenge.

In a previous work Anderson and Johnson[33] had noted that the primary target for antibody complement action on the leptospires was in the outer envelope (OE) as evidenced by electron microscopy. Also, the virulent leptospires were more resistant to the action of antibody complement than avirulent, leaving the impression that virulent leptospires possessed some component in the OE that may be associated with virulence. Subsequently, Auran et al[34] removed the OE of serovar Canicola by solubilizing it in sodium dodecyl sulfate (SDS) as evidenced by electron microscopy. Once the OE was removed the protoplasmic cylinder showed loss of intracellular organization. Immunization of hamsters followed by challenging with live organisms after 14 days was protective; 10 μg wet weight per animal of either formalinized whole cells (WC) or OE, protected hamsters from death and kidney infection.

Bey et al[35] quantitatively compared the immunogenicity of lyophilized leptospiral WC and OE vaccines from virulent and avirulent strains in hamsters, using the criteria of 50% protection from death (PD50D) and kidney protection (PD50K). Leptospira serovars evaluated were Canicola, Icterohaemorrhagiae, Pomona and Grippotyphosa. Results from these studies revealed that the OE and WC from virulent strains were more immunogenic and protective than the OE or WC from avirulent strains. Combining the OE from virulent strains of these four serovars and Hardjo formed a pentavalent OE vaccine, which had satisfactory immunogenic potency in hamsters and cattle.[36]

In 1975, Takashima and Yanagawa[37] evaluated the immunogenicity of leptospiral OE and the cell wall extracted with SDS. Results of these studies conducted in guinea pigs supported that the OE was a better immunogen than lyophilized WC, which was better than the cell wall extracted with SDS. The protein component of the OE was least protective. In addition, it took more immunogen to protect guinea pigs from renal infection than death. Siddique and Shah[38] evaluated outer envelope hexavalent (Pomona, Canicola, Hardjo, Icterohaemorrhagiae, Grippotyphosa, Swajizak) vaccine in hamsters. Animals given 10 mg dose developed higher MAT titres and more protection against challenge with Pomona as compared to those given 1 mg dose.

The leptospiral structural component that lies under the OE is the protoplasmic cylinder (PC) . Hamsters immunized with various doses of PC from virulent leptospires and challenged 14 days later had similar PD50D values as the OE and WC.[39] Further, dogs immunized with one mg dry weight PC had the greatest number of sensitized lymphocytes, as monitored by blast transformation.

Outer membrane proteins

OMPs as a whole or fractionated, conserved proteins among pathogenic leptospires that can generate cross protection against various serovars has become a major focus of current leptospirosis vaccine research.

Zhang et al[40] prepared an OMP vaccine of 39 kDa molecular weight hydrophobic protein and tested in guinea pigs. The vaccine was found to confer a solid immunity against challenge similar to that observed with a whole cell vaccine. Haake et al[41] examined the immunoprotective capacity of leptospiral transmembrane porin, Omp L1 and Lip41 lipoprotein from Grippotyphosa in hamsters. Hamsters immunized with E. coli membrane expressing both the proteins protected against challenge than vaccinated with either protein alone, showing synergistic activity of the proteins. A steric hindrance of OmpL1 by LipL41 has been proposed for this activity.[42] Srivastava and Tiwari[43] demonstrated that OMP from Leptospira spp. was cross-reactive.

Zhang et al[44] identified BMD - 3A and BMD - 10 genes in L. interrogans serovar Lai responsible for the expression of antigens important in the generation of immune response against leptospiral infection. Later, Jiang et al[45] reported the cloning and expression of two proteins of approximate molecular mass of 68 and 23 kDa from L. interrogans serovar Lai; p68 elicited a strong immune response (MAT titres 1:524, 288) in guinea pigs and generated a titre of 1:262, 144 in rabbits. The same workers reported that the vaccination of guinea pigs with DNA recombinant plasmid for p68 protected against virulent L. interrogans serovar Lai. The level of protection in p68-vaccinated group was 100% as against 75% in DNA vaccinated group.[46]

Haake et al[47] demonstrated LipL32 protein as the most abundant protein expressed by a conserved gene of pathogenic leptospires. This is also called hemolysis-associated protein (Hap-1). OMP L1 in combination with Lip32 had no protective activity in contrast to Lip41 reported earlier.[48] However, studies using gene for vaccination have revealed that LipL32 could be a protective immunogen.[48] Adenovirus expressed Lip32 protein has been reported to induce significant level of protection in gerbils.[49] Other virulent-associated surface exposed outer membrane proteins include the Lig proteins; Lig A consists only of Ig-like domains, whereas Lig B has an additional unique domain at the C-terminal.[50] Serum samples collected from Leptospira infected dogs or rats showed reactivity with LigA and LigB proteins while serum samples from vaccinated animal showed no reactivity, indicating that these proteins are up-regulated during infection.[51],[52] Further, in a mouse model the Lig proteins elicited protective immunity against challenge with the homologous serovar Manilae as well as the heterologous serovar Icterohaemorrhagiae.[51]

A novel approach to enhance the immunogenicity of the proteins shown to be exhibiting synergism is to attempt eukaryotic expression of fusion gene encoding these protein antigens. Yan et al[53] constructed L. interrogans LipL32/ 1-ompL1/ 1 fusion gene and achieved the expression in Pichia pastoris The recombinant protein was able to react with antibodies against this fusion protein raised in rabbit. The same group[54] later demonstrated the immunogenicity of this fusion protein using rabbit antisera and human patients' sera.

Lipopolysaccharide

The variation in the carbohydrate composition of LPS reflect the antigenic diversity among pathogenic leptospires. Reports have shown that it generates serovar specific immunity. Faine et al[55] isolated a lipopolysaccharide from leptospires, designated F4. This material was capable of protecting mice from death only when given in doses of 50 mg/ animal in Freund's incomplete adjuvant. Subsequently, Adler and Faine[56] found that rabbit antisera against leptospiral LPS protected hamsters from infection only if agglutinins were concomitantly present, indicating that the lipopolysaccharide may not be an important protective antigen. This was also supported by the findings that cattle vaccinated with pentavalent vaccine were vulnerable to the infection by serovar Hardjo despite the presence of high anti-LPS antibody titres.[57] Contrary to this, a recent report indicates that LPS from L. biflexa serovar Patoc was cross protective to hamsters when challenged with L. interrogans serovar Manilae.[58] Immunization protected hamsters from infection and prevented renal carrier stage. Srivastava[59] reported that purified LPS from serovar Pyrogenes was able to generate antibodies in rabbits responsible for lysis of live leptospires. Though this is indicative of the protective efficacy of LPS, more studies are required to arrive at a firm conclusion.


 ~ DNA Vaccines Top


The use of a DNA construct encoding leptospiral proteins is a promising new approach for vaccination against leptospirosis. Several studies using flaB2 gene have been done.[60],[61],[62] The cpG motif, found within the gene and the vector was immunostimulatory and was thought to act as an adjuvant for DNA vaccines.

Another study with DNA vaccine expressing Hap 1/LipL32 of L. interrogans serovar Autumnalis or Grippotyphosa, used in gerbils showed cross-protection against challenge with Canicola.[49]

Constraints in leptospirosis vaccine development and use

Since the vaccines largely confer serovar-specific immunity, continuous epidemiological monitoring of the prevalence of Leptospira serovars in a zone or region is desired to select the correct serovars for incorporating into the vaccine. MAT may be useful in investigating serovar-distribution provided antibodies are monitored at regular intervals, especially when new animals have been introduced in the herd.

While investigating the seroprevalence, care should be taken in interpreting the results since no test can differentiate antibodies generated in animals after the vaccination from those developed after an infection. When more than one serovar is chosen to prepare a vaccine, scientific data should be available to exclude any possibility of suppression of immune response to any of the serovar(s) added in the vaccine. Repeated booster immunization may not provide sufficient immunity against such serovars.

Development of leptospirosis vaccines is an arduous and time-consuming process. Unlike many other bacteria, spirochetes require fastidious growth conditions. Bulk promotion of organisms may not be achieved satisfactorily. Use of bio-fermentor may or may not enhance the growth of several serovars, e.g., Canicola.

The potency testing of leptospirosis is a cumbersome process. According to the current United States Standard requirements for Veterinary Biologicals, it requires large number of hamsters. This is time-intensive and has large associated test variances. Due to increased awareness and social concern, use of animals is being restricted prompting scientists to device in vitro tests.

The Center for Veterinary Biologics in USA (USDA-APHIS) has developed an antigen capture ELISA for testing of leptospirosis vaccines containing Canicola, Grippotyphosa and Icterohaemorrhagiae and Pomona. The monoclonal antibody, used in ELISA detects lipo-oligosaccharide moiety of leptospiral antigens. This is another constraint since in recent years membrane proteins have been increasingly found to be conferring protection in animals.

 
 ~ References Top

1.Ayyar VK. A note on an outbreak of leptospiral jaundice among Madras hounds. Indian J Vet Sci 1932; 2: 169.  Back to cited text no. 1    
2.Adinarayanan N, Jain NC, Chandiramani HK, Hajela SK. Studies on leptospirosis among bovines in India: A preliminary report on the occurrence in cattle based on serological evidence. Indian Vet J 1960; 37 :251.  Back to cited text no. 2    
3.Sane CR, Deshpande, B.R.. Record of detection of Leptospira Pomona infection as a cause of abortion in calves - letters to the Editor. IVJ. Indian Vet J 1965; 42 :75.  Back to cited text no. 3    
4.Rajasekhar M, Nanjiah RD. Animal leptospirosis in Mysore state: A serological study. Indian Vet J 1971; 48 :1087.  Back to cited text no. 4    
5.Srivastava SK, Singh SP, Srivastava NC. Seroprevalence of leptospirosis in animals and man in India. Indian J Comp Microbiol Immunol Infect Dis 1983; 4 :243.  Back to cited text no. 5    
6.Venkatraman V, Jaganathan PD. An outbreak of leptospiral infection in bovine in Madras state. Indian Vet J 1961; 38: 844.  Back to cited text no. 6    
7.Srivastava SK, Verma R, Harbola PC. Seroprevalence of leptospirosis in animals and man in India. Indian J Anim Sci 1991; 60 :1439-41.  Back to cited text no. 7    
8.Ratnam S, Everard CO, Alex C. A pilot study on the prevalence of leptospirosis in Tamil Nadu state. Indian Vet J 1994; 71 :1059-63.  Back to cited text no. 8    
9.Srivastava SK, Kumar AA. Seroprevalence of leptospirosis in animals and human beings in various regions of the country. Indian J Comp Microbiol Immunol Infect Dis 2003; 24 :155-9.  Back to cited text no. 9    
10.Broom JC. The protective value of Leptospiral vaccines in hamsters. Vet Rec 1949; 11 :127-30.  Back to cited text no. 10    
11.Brunner KT, Meyer KF. Immunization of hamsters and dogs against experimental leptospirosis. J Immun 1950; 64 ;365-72.  Back to cited text no. 11    
12.Hill FL, Wyeth TK. Serological reactions against L. int . sr. Inalapcas after vaccination. N Zealand Vet J 1991; 39: 32-3.  Back to cited text no. 12    
13.Venugopal K, Ratnam S. Preparation and standardization of trivalent leptospiral vaccine. Indian Vet J 1991; 68 :108-11.  Back to cited text no. 13    
14.Brown AL, Jensen JH, Creamer AA, Scheidy SF. Evaluation of a Leptospira bacterin prepared in culture medium. Vet Med 1955; 50 :167-71.  Back to cited text no. 14    
15.Hoag WG, Bell WB. An immunogenic agent for the protection of cattle against Leptospira pomona. Am J Vet Res 1955; 16 :381-5.  Back to cited text no. 15  [PUBMED]  
16.Bolin CA, Zuerner RL, Traueba G. Effect of vaccination with a pentavalent Leptospiral vaccine containing L.int. Sr. hardjo type hardjobovis on infection of cattle. Am J Vet Res 1989; 50 :2004-8.  Back to cited text no. 16    
17.Palit A, Alexander AM, Slacer B, Taylor C. Efficacy of L. interrogans serovar pomona and copenhageni and L. borgpetersenii serovar hardjo vaccine in cattle NZ Vet J 1996; 44 :64-6.  Back to cited text no. 17    
18.Dhaliwal CS, Murray PD, Dobson H, Montgomery J, Ellis WA. Effect of vaccination against hardjo on milk production and infertility in dairy cattle. Vet Rec 1996: 38 :334-5.  Back to cited text no. 18    
19.Bey RF, Johnson RC. Leptospiral vaccines: Immunogenicity of protein-free medium cultivated whole cell bacterins in swine. Am J Vet Res 1983; 44: 2299-301.  Back to cited text no. 19  [PUBMED]  
20.Hodges, RT, Young GW, Thomson JT. The efficacy of a leptospirosis vaccine in preventing leptospiruria in pigs. N Z Vet J 1985; 33 :31-4.  Back to cited text no. 20    
21.Francois S, Gualtiere C, Drab S, Creixell B, Capelletti G, Anthony I. Serological study after vaccination against leptospirosis in pigs. Veterinaria Argentina 1995; 12 :530-3.  Back to cited text no. 21    
22.Heath KR, Box PG. Immunity to leptospirosis: Antibodies in vaccinated and infected dogs. J Comp Path 1975; 75 :125-36.  Back to cited text no. 22    
23.Danczig E, Polner A. Vaccination against leptospirosis in a pig herd. Magyar allatorvosal Lapja. 1997; 119: 420-4.  Back to cited text no. 23    
24.Bramel RG, Scheidy SF. The effect of revaccination of horses and cattle with Leptospira pomona bacteria. J Am Vet Med Assoc 1956; 128 :399-400.  Back to cited text no. 24  [PUBMED]  
25.Hartman EG, van Houten M, van der Donk JA, Frik JF. Serodiagnosis of canine leptospirosis by solid phase enzyme linked immunosorbent assay. Vet Immunol Immunopathol 1984; 7 :33-42.  Back to cited text no. 25  [PUBMED]  
26.Broughton ES, Scarnell J. Prevention of renal carriage of leptospirosis in dogs by vaccination. Vet Rec 1985; 117 :307-11.  Back to cited text no. 26  [PUBMED]  
27.Barr SC, McDonough PL, Scipioni BR, Starr JK Serological response of dogs given a commercial vaccine against L. interrogans serovar Pomona and L. kirschneri serovar Grippotyphosa. Am J Vet Res 2005; 66 :1780-4.  Back to cited text no. 27    
28.Kenzy SG, Gillespie RW, Lee JH. Comparison of Leptospira pomona bacterin and attenuated live culture vaccine for control of abortion in cattle. J Am Vet Med Assoc 1961; 139: 452-4.  Back to cited text no. 28  [PUBMED]  
29.Hubert WT, Miller JN. Studies in experimental leptospirosis. The immunogenicity of Leptospira icterohaemorrhagiae attenuated by gamma irradiation. J Immun 1965; 95: 759-64.  Back to cited text no. 29    
30.Babudieri B, Castelli M, Risoni F. Comparative tests with formalinized and irradiated vaccines against leptospirosis. Bull WHO 1973; 48 :587-90.  Back to cited text no. 30    
31.Stalheim OH. Vaccination against leptospirosis: Protection of hamsters and swine against renal leptospirosis by killed, intact, gamma irradiated or dihydrostreptomycin exposured Leptospira pomona. Am J Vet Res 1967; 28: 1671-6.  Back to cited text no. 31  [PUBMED]  
32.Fish NA, Kingscote B. Protection of gilts against leptospirosis by use of a live vaccine. Can Vet J 1973; 14 :12-5.  Back to cited text no. 32  [PUBMED]  [FULLTEXT]
33.Anderson DL, Johnson RC. Electron microscopy of immune disruption of leptospires: Action of complement and Iysozyme. J Bact 1968 ;95 :2293-309.  Back to cited text no. 33    
34.Auran NE, Johnson RC, Ritzi DM. Isolation of the outer sheath of Leptospira and its immunogenic properties in hamsters. Infect Immun 1972; 5: 968-75.  Back to cited text no. 34  [PUBMED]  [FULLTEXT]
35.Bey RF, Auran NE, Johnson RC. Immunogenicity of whole cell and outer envelope vaccines in hamsters. Infect Immun 1974; 10: 1051-6.  Back to cited text no. 35  [PUBMED]  [FULLTEXT]
36.Tripathy DN, Hanson LE, Mansfield ME. Evaluation of the immune response of cattle to Leptospira bacterins. Am J Vet Res 1976; 37 :51-5.  Back to cited text no. 36  [PUBMED]  
37.Takashima I, Yanagawa R. Immunizing effects of structural components of Leptospira icterohaemorrhagiae. Zentbl Bakt ParasitKde 1975; 233 :93-8.  Back to cited text no. 37  [PUBMED]  
38.Siddique H, Shah SM. Evaluation of polyvalent Leptospiral vaccine in hamsters. Indian Vet J 1990; 67: 1006-10.  Back to cited text no. 38    
39.Bey RF, Johnson RC. Immunogenicity and humoral and cell mediated immune response to Leptospiral whole cell, outer envelope and protoplasmic cylinder vaccines in hamsters and dogs. Am J Vet Res 1982; 43: 835-40.  Back to cited text no. 39  [PUBMED]  
40.Zhang Y, Qie M, Zeng X, Cheng J, Wu J, Liu J. The effect of a vaccine made from 39kd hydrophobic outer membrane protein of Leptospira interrogans on neurohumoral and red cell immunity function of the guinea pigs. Hua Xi Yi Ke Da Xue Xue Bao 1998 ;29: 117-21.  Back to cited text no. 40    
41.Haake DA, Muzel MK, DcCoy AM, Mitward F. Leptospiral outer membrane protein OmpL1 and LipL 41 exhibit synergistic immunoprotection. Infect Imm 1999;67:6572-82.  Back to cited text no. 41    
42.Cullen PA, Haake DA, Adler B. Outer membrane protein of pathogenic spirochetes. FEMS Microbiol Rev 2004; 28 ;291-318.  Back to cited text no. 42    
43.Srivastava SK, Tiwari V. Immunoreactivity of outer membrane protein of Leptospira interrogans serovar pyrogenes. Indian J Comp Microbiol Immunol 2000 ;21 :11-4.   Back to cited text no. 43    
44.Zhang M, Bao L, Yan R, Li S. Transcript expression of the CPL 5x, BMD-3A, BMD-10 of Leptospira interrogans . Hua His Ko Ta Husuh Hsueh 1994; 25: 365-8.   Back to cited text no. 44  [PUBMED]  
45.Jiang N, Dai B, Li S, Zhao H, Fang Z, Wu W, et al . Immunogenecity of expressed protein p68 from recombinant plasmid rpDJt in L. interrogans serovar lai. Hua Xi Yi Ke Da Xue Xue Bao 1997; 28 :122-7.   Back to cited text no. 45    
46.Dai B, Jiang N, Li S, Fang Z, Zhao H, Wu W, et al . Immunoprotection in guinea pigs using DNA recombinant plasmid rpDJt and expressed protein P68 in L. interrogans serovar lai. Hua Xi Yi Ke Da Xue Xue Bao 1998; 29 :248-51.   Back to cited text no. 46    
47.Haake DA, Chao G, Zuerner RL, Barnett JK, Barnett D, Mazel M, et al . The Leptospiral OMP LipL32 is a lipoprotein expressed during mammalian infection. Infect Immun 2000; 68 :2276-85.   Back to cited text no. 47    
48.Branger C, Sonrier C, Chatrenet B, Klonjkowski B, Ruvoen-clovet N. Identification of the haemolysis-associated protein 1 as a cross-protective immunogen of L. interrogans by adenovirus-mediated vaccination. Infect Immun 2001; 69 :6831-8.  Back to cited text no. 48    
49.Branger C, Chatervet B, Gauvrit A, Aviat F. Protection against L. interrogans sensu lato challenge by DNA immunization with gene encoding Hap1. Infect Immun 2005 ;73 :4062-9.   Back to cited text no. 49    
50.Matsunaga J, Barocchi MA, Croda J, Young TA, Sachez Y, Siqueira I, et al . Pathogenic Leptospira species express surface exposed proteins belonging to the bacterial immunoglobulin family. Mol Microbiol 2003; 49 :929-45.  Back to cited text no. 50    
51.Koizumi N, Watanabe H. Leptospirosis vaccine: Past, present and future. J Postgrad Med 2005; 51 :210-4.  Back to cited text no. 51  [PUBMED]  [FULLTEXT]
52.Palaniappan RU, Chang YF, Hassan F, McDonough SP, Pough M. Expression of Ig like protein by L. interrogans . J Med Microbiol 2004; 53 :975-84.   Back to cited text no. 52    
53.Yan J, Zhao SF, Mao YF, Ruan P, Luo YH, Li SP, et al . Eukaryotic expression of Leptospira interrogans lipL32/1-ompL1/1 fusion gene encoding genus-specific protein antigens and the immunoreactivity of expression products. Zhejiang Da xue xue Baoyi xue Ban 2005; 34 :33-7.  Back to cited text no. 53    
54.Luo DJ, Yan J, Maoyf, Lis P, Luo YH, Li LW. Construction and application of prokaryotic expression system of L. interrogans LipL2/1-LipL1/1 fusion gene. Zhejiang Daxue Xue Bao yixue Ban 2005; 34 ;27-32.  Back to cited text no. 54    
55.Faine S, Adler B, Ruta G. Mechanisms of immunity to Leptospira . Aust J Exp Biol Med Sci 1974; 52 :301-10.  Back to cited text no. 55  [PUBMED]  
56.Adler B, Faine S. Serological and protective-antibody responses of rabbits to Leptospiral antigens. J Med Microbiol 1978; 11 :401-9.  Back to cited text no. 56  [PUBMED]  
57.Bolin CA, Casells JA, Zuerner RL, Trueba G. Effect of vaccination with a monovalent L. interrogans serovar hardjo type hardjobovis vaccine on type hardjobovis infection of cattle. Am J Vet Res 1991; 52 :1639-43.   Back to cited text no. 57    
58.Matsuo K, Isogai E, Araki Y. Control of immunologically crossreactive leptospiral infection by administration of lipopolysaccharides from a nonpathogenic strain of Leptospira biflexa . Microbiol Immunol 2000; 44: 887-90.  Back to cited text no. 58  [PUBMED]  
59.Srivastava SK. Properties of lipopolysaccharide antigen of Leptospira interrogans serovar Pyrogenes. Indian Vet J 2002; 79 :1201-2.  Back to cited text no. 59    
60.You Z, Dai B, Chen Z, Yan H, Fang Z, Li S, et al . Immunogenicity and immunoprotection of a Leptospiral DNA vaccine. Hua Xi Yi Da Xue Xue Bao 1999; 30 :128-32.  Back to cited text no. 60    
61.Wang M, Dai B, You Z, Fang Z, Wang Y. Construction of DNA vaccine including a chimeric gene encoding flagellin and outer membrane protein antigen from Leptospira interrogans serovar lai. Hua Xi Yike Daxue Xue Bao 2002; 33 :169-71.  Back to cited text no. 61  [PUBMED]  
62.Dai B, You Z, He P, Wang M, Wang Y. Analysis of cpG motif in endoflagellar gene and expression vector of Leptospiral DNA vaccine. Sichuan Da Xue Xue Bao Yi Xue Ban 2003; 34: 1-4.  Back to cited text no. 62  [PUBMED]  


    Tables

[Table - 1]

This article has been cited by
1 Identification of <i>ompL</i>1 and <i>lipL</i>32 Genes to Diagnosis of Pathogenic <i>Leptospira</i> spp. Isolated from Cattle
Hernández-Rodríguez Patricia,Gomez Ramirez Arlen,Baquero Mónica,Quintero Gladys
Open Journal of Veterinary Medicine. 2014; 04(05): 102
[Pubmed] | [DOI]
2 Evaluation of recombinant LigB antigen-based indirect ELISA and latex agglutination test for the serodiagnosis of bovine leptospirosis in India
Yosef Deneke,T. Sabarinath,Neha Gogia,Jonathan Lalsiamthara,K.N. Viswas,Pallab Chaudhuri
Molecular and Cellular Probes. 2014;
[Pubmed] | [DOI]
3 Report on the international workshop on alternative methods for Leptospira vaccine potency testing: State of the science and the way forward
William Stokes,Geetha Srinivas,Richard McFarland,Jodie Kulpa-Eddy,Warren Casey,Angela Walker,Hans Draayer,Randy Sebring,Karen Brown,Elisabeth Balks,Catrina Stirling,Eric Klaasen,Richard Hill,Byron Rippke,Kevin Ruby,David Alt,Suman Mukhopadhyay,Hajime Kojima,Nelson Johnson,Lori Rinckel,Vivian Doelling,Brett Jones
Biologicals. 2013; 41(5): 279
[Pubmed] | [DOI]
4 Leptospirosis-persistence of a Dilemma: An Overview with Particular Emphasis on Trends and Recent Advances in Vaccines and Vaccination Strategies
Amit Kumar Verma,Amit Kumar,K. Dhama,Rajib Deb,Anu Rahal,Mahima .,Sandip Chakrabort
Pakistan Journal of Biological Sciences. 2012; 15(20): 954
[Pubmed] | [DOI]
5 Determination of an infectious dose of Leptospira for the performance of challenge test in assessing the efficacy of Leptospira vaccines
Jirí Neperený,Josef Chumela,Vladimír Vrzal
Acta Veterinaria Brno. 2011; 80(3): 263
[Pubmed] | [DOI]
6 Improvement of trivalent leptospira vaccine by removal of anaphylactic agents
Gholamreza Moazenijula, A. R. Jabbari, M. Moradi Geravand, R. Banihashemi, A. Hajizadeh
Tropical Animal Health and Production. 2011;
[VIEW] | [DOI]
7 Leptospirosis vaccines
Wang, Z., Jin, L., Wegrzyn, A.
Microbial Cell Factories. 2007; 6(Art 39)
[Pubmed]



 

Top
Print this article  Email this article
Previous article Next article

    

© 2004 - Indian Journal of Medical Microbiology
Published by Wolters Kluwer - Medknow

Online since April 2001, new site since 1st August '04