Cell-Mediated Immune Response of the Mammary Gland in Guinea Pigs. I. Effect of Antigen Injection Into the Vaccinated and Unvaccinated Glands*

Background: Leptospirosis significantly impacts the economy of livestock farmers by causing reproductive failure and production losses in bovines. The control of bovine leptospirosis requires a combination of vaccination programme, biosecurity measures and chemotherapeutic regimens. Vaccination protect the clinical diseases and reduces/prevents renal colonisation of Leptospires and in turn reduces excretion of leptospires in urine which is a major source of environmental contamination. Some serovars of leptospires require cell mediated immunity apart from humoral immunity. This study was undertaken to develop prototype vaccine with prevalent serogroups to induce humoral and cell mediated immunity. Immunogenicity of the prototype vaccines and their safety were assessed experimentally in Guinea pigs.Methods: An inactivated oil adjuvant prototype pentavalent bovine leptospira vaccines with serogroups Australis, Hebdomadis, Hardjo, Javanica and Pomona which were prevalent in Tamil Nadu were developed and compared with the aluminium hydroxide gel adjuvant vaccine. The humoral immune response was assessed measuring antibodies by Microscopic Agglutination Test and Cell Mediated Immune response was assessed by lymphocyte proliferation assay. The ability of these vaccines to protect Guinea pigs against virulent Leptospires challenge was also demonstrated.Result: The prototype vaccine blended with oil adjuvants resulted in higher protective antibody titres of more than 6.64 log2 (≥1:100) than the aluminium hydroxide adjuvant blended vaccine. The protective antibody titres lasted upto 180 days, except for serogroup Javanica (150 days). The Montanide adjuvants were able to produce cell mediated immune response for protection against serovar Hardjo. Challenge study in guinea pigs showed complete protection following vaccination using pentavalent vaccine blended with Montanide adjuvants, while the aluminium hydroxide adjuvant was able to confer only partial protection. The Montanide blended prototype vaccines were also able to prevent renal colonisation of all five serogroups. This study shows the potential of the oil adjuvant blended multivalent vaccine for use in vaccination programmes against bovine leptospirosis.

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Vaccination with the major secretory protein of Legionella pneumophila induces cell-mediated and protective immunity in a guinea pig model of Legionnaires' disease.

Journal of Experimental Medicine ◽

10.1084/jem.169.3.691 ◽

1989 ◽

Vol 169 (3) ◽

pp. 691-705 ◽

Cited By ~ 51

Author(s):

S J Blander ◽

M A Horwitz

Keyword(s):

Immune Response ◽

Legionella Pneumophila ◽

Guinea Pigs ◽

Protective Immunity ◽

Secretory Protein ◽

Sublethal Dose ◽

Exact Test ◽

Cell Mediated Immune Response ◽

Legionnaires Disease ◽

Guinea Pig Model

We have examined the capacity of the major secretory protein (MSP) of Legionella pneumophila to induce humoral, cell-mediated, and protective immunity in a guinea pig model of Legionnaires' disease. MSP was purified to homogeneity by ammonium sulfate precipitation, molecular sieve chromatography, and ion-exchange chromatography. The purified MSP was nonlethal and nontoxic to guinea pigs upon subcutaneous administration. Guinea pigs immunized with a sublethal dose of aerosolized L. pneumophila or a subcutaneous dose of MSP developed a strong cell-mediated immune response to MSP. Such guinea pigs exhibited marked splenic lymphocyte proliferation and cutaneous delayed-type hypersensitivity to MSP in comparison with control animals. Guinea pigs immunized with MSP also developed a strong humoral immune response to MSP, as assayed by an ELISA. The median reciprocal antibody titer was 362 (range 45 to greater than 2,048) for immunized animals compared with less than 8 for controls. In contrast, guinea pigs immunized with a sublethal dose of L. pneumophila failed to develop anti-MSP antibody. Guinea pigs immunized with MSP and then challenged with a lethal aerosol dose of L. pneumophila exhibited highly significant protective immunity in each of five consecutive experiments. MSP induced protective immunity in dose-dependent fashion (40 greater than 10 greater than 2.5 greater than 0.6 micrograms MSP); vaccination with two doses of as little as 2.5 micrograms MSP induced significant protective immunity (p = 0.01, Fisher's Exact Test, two-tailed). Altogether, 21 (81%) of 26 animals immunized with 40 micrograms MSP survived challenge compared with 0 (0%) of 26 sham-immunized control animals (p = 7 x 10(-10), Fisher's Exact Test, two-tailed). MSP-immunized but not control guinea pigs were able to limit L. pneumophila multiplication in their lungs. This study demonstrates that (a) guinea pigs sublethally infected with L. pneumophila develop a strong cell-mediated immune response to MSP; (b) guinea pigs immunized with MSP develop a strong humoral and cell-mediated immune response to MSP; (c) guinea pigs immunized with MSP develop a very high level of protective immunity to lethal aerosol challenge with L. pneumophila; and (d) MSP-immunized animals are able to limit L. pneumophila multiplication in their lungs. MSP, an extracellular protein of an intracellular pathogen, has potential as a vaccine for the prevention of Legionnaires' disease. Secretory molecules of other intracellular pathogens may also have vaccine potential.

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