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Pilins from the B serogroup of Bacteroides nodosus: characterization, expression, and cross-protection.

Sequences of pilin genes from four strains of serogroup B of the ovine pathogen Bacteroides nodosus have been determined. These sequences permit comparisons of amino acid sequence between pilins from different subtypes (B1, B2, B3, B4) of the B serogroup and assessment of intraserogroup variation. Pili of B. nodosus strains 234 (B1) and 183 (B2) were produced by Pseudomonas aeruginosa harboring a plasmid-borne B. nodosus pilin gene, and these pili were used in sheep vaccination trials. Pili from strain 183 (B2) were found to be a senior antigen to pili from strains of other B subtypes, providing protection against footrot infection caused by strains of the other B subtypes. Pili of this strain are therefore the most suitable candidate for inclusion in a pilus-based vaccine. Pili of strain 234 from subtype B1, the reference strain of the B serogroup, provided poor protection against infection with other subtypes.

Amino Acid Sequence↗

Reinfection with Anaplasma phagocytophilum in BALB/c mice and cross-protection between two sympatric isolates.

Infection with Anaplasma phagocytophilum in white-footed mice results in partial protection against reinfection with the same agent. However, humans and domestic animals may be sequentially exposed to different isolates of the agent circulating in the same or adjacent foci. We investigated whether immune response to a tick-borne infection with A. phagocytophilum provides protection against homologous and heterologous challenges. BALB/c mice were infected with one of the two sympatric isolates of A. phagocytophilum via tick bite and challenged 16 weeks later by Ixodes scapularis nymphs infected with either the same or the alternative isolate. As controls, groups of infected mice were challenged by uninfected ticks to confirm an absence of reactivation of the original infection or groups of naive mice were fed upon by ticks from cohorts used for an infectious challenge. Xenodiagnostic I. scapularis larvae were fed upon each mouse at 14 and 21 days postchallenge (PCH) and tested for the presence of A. phagocytophilum as freshly molted nymphs. Blood samples for quantitative PCR were collected at 7, 14, 21, and 70 days PCH. Serum samples were collected weekly to monitor development of immune response. The proportion of infected animals, levels of bacteremia, and the prevalence of infection in xenodiagnostic ticks were higher in groups of control mice exposed to A. phagocytophilum for the first time than in mice reinfected with either homologous or heterologous isolates. The presence of antibodies against A. phagocytophilum did not protect mice from a challenge with either homologous or heterologous isolates, however the ensuing reinfection was significantly milder and of a shorter duration than the first infection with either isolate.

Anaplasma phagocytophilum↗

Cross-protective efficacy of a prophylactic Leishmania donovani DNA vaccine against visceral and cutaneous murine leishmaniasis.

The fucose-mannose ligand (FML) complex of Leishmania donovani is a promising vaccine candidate against murine and canine visceral leishmaniasis, and its main component is a 36-kDa nucleoside hydrolase (NH36). In this study, we tested the immune response and protection induced by the purified FML, the recombinant NH36 (rNH36), and NH36 DNA vaccines against the agents of visceral (L. chagasi) and cutaneous (L. mexicana) leishmaniasis in BALB/c mice. Mice developed weak humoral response to the vaccines alone, except for those immunized with FML. However, all three vaccine groups presented elevated immunoglobulin G (IgG), IgG1, and IgG2a levels after infection with L. chagasi, whereas no differences were observed between vaccine and control groups after infection with L. mexicana. A strong intradermal reaction to L. donovani and L. mexicana antigens was observed in mice immunized with rNH36 or FML, whereas mice immunized with NH36 DNA only reacted against L. donovani antigens. Experimental infection of immunized mice demonstrated that FML and rNH36 induced significant protection against L. chagasi infection with reductions in parasite loads of 79%. FML also conferred partial protection against L. mexicana infection. The best protection was observed in mice immunized with the VR1012-NH36 DNA vaccine, which induced an 88% reduction in L. chagasi parasite load and a 65% reduction in L. mexicana lesion size. Fluorescence-activated cell sorting analysis indicated the DNA vaccine induced a two- to fivefold increase in gamma interferon-producing CD4(+) T cells, indicating a Th1-type immune response. Our results showed that the NH36 DNA vaccine induced a strong immunoprotection against visceral and cutaneous leishmaniasis, suggesting that this DNA vaccine represents a very good candidate for use against several Leishmania species.

Animals↗

Starvation-induced cross protection against osmotic challenge in Escherichia coli.

Stationary-phase Escherichia coli cultures showed enhanced osmotic resistance as compared with cultures in mid-logarithmic growth or preadapted to osmotic stress. The osmotolerance that developed during starvation or osmotic adaptation required de novo protein synthesis. Of the 22 polypeptides induced during osmotic shock, five were also starvation proteins.

Bacterial Proteins↗

Live, attenuated influenza A H5N1 candidate vaccines provide broad cross-protection in mice and ferrets.

BACKGROUND: Recent outbreaks of highly pathogenic influenza A H5N1 viruses in humans and avian species that began in Asia and have spread to other continents underscore an urgent need to develop vaccines that would protect the human population in the event of a pandemic. METHODS AND FINDINGS: Live, attenuated candidate vaccines possessing genes encoding a modified H5 hemagglutinin (HA) and a wild-type (wt) N1 neuraminidase from influenza A H5N1 viruses isolated in Hong Kong and Vietnam in 1997, 2003, and 2004, and remaining gene segments derived from the cold-adapted (ca) influenza A vaccine donor strain, influenza A/Ann Arbor/6/60 ca (H2N2), were generated by reverse genetics. The H5N1 ca vaccine viruses required trypsin for efficient growth in vitro, as predicted by the modification engineered in the gene encoding the HA, and possessed the temperature-sensitive and attenuation phenotypes specified by the internal protein genes of the ca vaccine donor strain. More importantly, the candidate vaccines were immunogenic in mice. Four weeks after receiving a single dose of 10(6) 50% tissue culture infectious doses of intranasally administered vaccines, mice were fully protected from lethality following challenge with homologous and antigenically distinct heterologous wt H5N1 viruses from different genetic sublineages (clades 1, 2, and 3) that were isolated in Asia between 1997 and 2005. Four weeks after receiving two doses of the vaccines, mice and ferrets were fully protected against pulmonary replication of homologous and heterologous wt H5N1 viruses. CONCLUSIONS: The promising findings in these preclinical studies of safety, immunogenicity, and efficacy of the H5N1 ca vaccines against antigenically diverse H5N1 vaccines provide support for their careful evaluation in Phase 1 clinical trials in humans.

Animals↗

A dhfr-ts- Leishmania major knockout mutant cross-protects against Leishmania amazonensis.

E10-5A3 is a dhfr-ts- Leishmania major double knockout auxotrophic shown previously to induce substantial protection against virulent L. major infection in both genetically susceptible and resistant mice. We investigated the capacity of dhfr-ts- to protect against heterologous infection by L. amazonensis. The degree of protection was evaluated by immunization of BALB/c or C57BL/6 mice with E10-5A3, followed by L. amazonensis challenge. Whether immunized by subcutaneous (SC) or intravenous (IV) inoculation, susceptible and resistant mice displayed a partial degree of protection against challenge with virulent L. amazonensis. SC-immunized BALB/c mice developed lesions 40 to 65% smaller than non immunized mice, while IV immunization led to protection ranging from 40 to 75% in four out of six experiments compared to non immunized animals. The resistant C57BL/6 mice displayed comparable degrees of protection, 57% by SC and 49% by IV immunization. Results are encouraging as it has been previously difficult to obtain protection by SC vaccination against Leishmania, the preferred route for human immunization.

Animals↗

Acid adaptation of Listeria monocytogenes strains does not offer cross-protection against an activated lactoperoxidase system.

Listeria monocytogenes has been implicated in foodborne illness outbreaks involving several types of cheeses made from acidified milk. Acid shock response (ASR) and acid tolerance response (ATR) could be possible reasons for its survival. The ASR and ATR of three strains of L. monocytogenes (V7, V37, and CA) in skim milk acidified to pH 4.0 and 3.5 with lactic acid and held at 32 degrees C were studied. Studies were also done to determine if acid adaptation of the organism enhanced survival in the presence of an activated lactoperoxidase system. The cells were directly shocked at pH 4.0 and 3.5 in skim milk to study the ASR. To study the ATR, cells were initially adapted in skim milk at a mild pH of 5.5 for the equivalent of one generation before being shocked at pH 4.0 and 3.5 in skim milk. Cells adapted at pH 5.5 in tryptic soy broth without dextrose and nonadapted cells were challenged at pH 4.5 in skim milk with or without an activated lactoperoxidase system. In all cases, viability and pH were measured 24 or 48 h after challenge. In pH 4.0 skim milk, for all three strains, the adapted cell population survived better (0.5 to 1.0 log higher) than that of nonadapted cells for 24 h. In pH 3.5 skim milk, the acid-adapted populations of all three strains were 3 to 4 logs greater than those of nonadapted cells at 6 h. The acid adapted cells of all three strains had survival rates similar to those of the nonadapted cells at pH 4.5 both in the presence and absence of an activated lactoperoxidase system. It was also evident that these strains do not exhibit an adaptive ATR at pH 4.5, although they do at lower pH levels (pH 4.0 and 3.5). Survival due to the ATR was better seen at pH 3.5 than at pH 4.0.

Adaptation, Physiological↗

Evaluation of cross-protection afforded by a Salmonella Choleraesuis vaccine against Salmonella infections in pigs under field conditions.

This field study investigated the efficacy of a Salmonella Choleraesuis live vaccine (Argus SC) to reduce the number of infections with Salmonella. Twelve groups of about 380 pigs each were randomly allocated to either vaccination (V) or no vaccination (C). The vaccine was applied orally at 3 and 16 weeks. Forty pigs per group were blood sampled at 3, 10, 16, and 24 weeks to detect possible antibodies against Salmonella. The prevalence of Salmonella in the lymph nodes was the major variable. In the V groups, only 0.6% of the lymph nodes were positive, whereas 7.2% were positive in the C groups (p < 0.001). The percentage of seropositive pigs at 24 weeks (cut-off OD > 10) was 26% and 9% in the V and C groups, respectively (p < 0.001). The present study documented that vaccination with a live modified S. Choleraesuis vaccine is a useful tool to lower the prevalence of Salmonella in swine herds.

Animals↗

Cross-protection studies with vaccine strain H-120 of infectious bronchitis virus using ciliary activity.

Forty 3-day-old chickens were immunized intratracheally and another 40 intranasally-intraocularly with vaccine strain H-120 of infectious bronchitis virus (IBV). The chickens were divided into groups of five and each group was challenged intratracheally or intranasally-intraocularly with one of 8 different heterologous strains of IBV 4 weeks after vaccination. The vaccinated chickens were protected against challenge with three heterologous strains (Massachusetts M41, B and AEG), showing 89, 86 and 89% ciliary activity, respectively, but were not protected against challenge with strains D-3896 and D-3128. Clinical signs and/or a reduction in ciliary activity was observed neither for the vaccinated nor for the unvaccinated groups challenged with strains Sz, D-207 and D-212. This suggests that these isolates have no primary pathogenic role in broiler flocks. The remaining 5 strains (M41, B, AEG, D-3896 and D-3128) caused mild respiratory signs and ciliostasis in birds of the unvaccinated groups.

Animals↗

Previous infection with West Nile or St. Louis encephalitis viruses provides cross protection during reinfection in house finches.

House finches are competent hosts for both West Nile and St. Louis encephalitis viruses and frequently become infected during outbreaks. In the current study, House finches were infected initially with either West Nile or St. Louis encephalitis viruses and then challenged 6 weeks post infection with either homologous or heterologous viruses. Although mortality rates were high during initial infection with West Nile virus, prior infection with either virus prevented mortality upon challenge with West Nile virus. Prior infection with West Nile virus provided sterilizing immunity against both viruses, whereas prior infection with St. Louis encephalitis virus prevented viremia from St. Louis encephalitis virus, but only reduced West Nile virus viremia titers. Immunologic responses were measured by enzyme immunoassay and plaque reduction neutralization tests. Heterologous challenge with West Nile virus in birds previously infected with St. Louis encephalitis virus produced the greatest immunologic response, markedly boosting antibody levels against St. Louis encephalitis virus. Our data have broad implications for free-ranging avian serological diagnostics and possibly for the recent disappearance of St. Louis encephalitis virus from California.

Animals↗

Cross-protection of mu and delta opioid receptors in the mouse vas deferens.

Opioid receptors in the C57/BL mouse vas deferens can be irreversibly blocked by pre-treatment with beta-chlornaltrexamine. Pre-incubation with the highly selective delta-receptor antagonist ICI 174864 concentration-dependently protected delta-receptors from inactivation, but the same concentrations similarly protected mu receptors. Pre-incubation with selective mu-receptor agonist, [D-Ala2, MePhe4, Gly(ol)5]enkephalin, also protected both mu and delta receptors to the same degree. Neither ligand protected k-opioid receptors. The results suggest that there may be a structural interaction between mu and delta receptors in the mouse vas deferens.

Animals↗