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A host-restricted viral vector for antigen-specific immunization against Lyme disease pathogen.

ABSTRACT: Newcastle disease virus (NDV) is an avian virus that is attenuated in primates and is a potential vaccine vector for human use. We evaluated NDV as a vector for expressing selected antigens of the Lyme disease pathogen Borrelia burgdorferi. A series of recombinant NDVs were generated that expressed intracellular or extracellular forms of two B. burgdorferi antigens: namely, the basic membrane protein A (BmpA) and the outer surface protein C (OspC). Expression of the intracellular and extracellular forms of these antigens was confirmed in cultured chicken cells. C3H or Balb/C mice that were immunized intranasally with the NDV vectors mounted vigorous serum antibody responses against the NDV vector, but failed to mount a robust response against either the intracellular or extracellular forms of BmpA or OspC. By contrast, a single immunization of hamsters with the NDV vectors via the intranasal, intramuscular, or intraperitoneal route resulted in rapid and rigorous antibody responses against the intracellular or extracellular forms of BmpA and OspC. When groups of hamsters were separately inoculated with various NDV vectors and challenged with B. burgdorferi (10(8)cells/animal), immunization with vector expressing either intracellular or extracellular BmpA was associated with a significant reduction of the pathogen load in the joints. Taken together, our studies highlighted the importance of NDV as vaccine vector that can be used for simple yet effective immunization of hosts against bacterial infections including Lyme disease.

SUBMITTER: Xiao S

PROVIDER: S-EPMC3138909 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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A host-restricted viral vector for antigen-specific immunization against Lyme disease pathogen.

Xiao Sa S Kumar Manish M Yang Xiuli X Akkoyunlu Mustafa M Collins Peter L PL Samal Siba K SK Pal Utpal U

Vaccine 20110519 32

Newcastle disease virus (NDV) is an avian virus that is attenuated in primates and is a potential vaccine vector for human use. We evaluated NDV as a vector for expressing selected antigens of the Lyme disease pathogen Borrelia burgdorferi. A series of recombinant NDVs were generated that expressed intracellular or extracellular forms of two B. burgdorferi antigens: namely, the basic membrane protein A (BmpA) and the outer surface protein C (OspC). Expression of the intracellular and extracellul ...[more]

PMID: 21600949

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Project description:Multistrain microbial pathogens often induce strain-specific antibody responses in their vertebrate hosts. Mothers can transmit antibodies to their offspring, which can provide short-term, strain-specific protection against infection. Few experimental studies have investigated this phenomenon for multiple strains of zoonotic pathogens occurring in wildlife reservoir hosts. The tick-borne bacterium Borrelia afzelii causes Lyme disease in Europe and consists of multiple strains that cycle between the tick vector (Ixodes ricinus) and vertebrate hosts, such as the bank vole (Myodes glareolus). We used a controlled experiment to show that female bank voles infected with B. afzelii via tick bite transmit protective antibodies to their offspring. To test the specificity of protection, the offspring were challenged using a natural tick bite challenge with either the maternal strain to which the mothers had been exposed or a different strain. The maternal antibodies protected the offspring against a homologous infectious challenge but not against a heterologous infectious challenge. The offspring from the uninfected control mothers were equally susceptible to both strains. Borrelia outer surface protein C (OspC) is an antigen that is known to induce strain-specific immunity. Maternal antibodies in the offspring reacted more strongly with homologous than with heterologous recombinant OspC, but other antigens may also mediate strain-specific immunity. Our study shows that maternal antibodies provide strain-specific protection against B. afzelii in an ecologically important rodent reservoir host. The transmission of maternal antibodies may have important consequences for the epidemiology of multistrain pathogens in nature.IMPORTANCE Many microbial pathogen populations consist of multiple strains that induce strain-specific antibody responses in their vertebrate hosts. Females can transmit these antibodies to their offspring, thereby providing them with short-term strain-specific protection against microbial pathogens. We investigated this phenomenon using multiple strains of the tick-borne microbial pathogen Borrelia afzelii and its natural rodent reservoir host, the bank vole, as a model system. We found that female bank voles infected with B. afzelii transmitted to their offspring maternal antibodies that provided highly efficient but strain-specific protection against a natural tick bite challenge. The transgenerational transfer of antibodies could be a mechanism that maintains the high strain diversity of this tick-borne pathogen in nature.

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A host-restricted viral vector for antigen-specific immunization against Lyme disease pathogen.

Publications

A host-restricted viral vector for antigen-specific immunization against Lyme disease pathogen.

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