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PubMed2003

Comparison of hamster and pony challenge models for evaluation of effect of antigenic drift on cross protection afforded by equine influenza vaccines.

REASONS FOR PERFORMING STUDY: Vaccination and challenge studies in ponies are the most relevant experimental system for predicting whether strains included in equine influenza vaccines are relevant, but they are difficult to perform. OBJECTIVES: In order to investigate the feasibility of using a small animal model, results of a cross-protection study in hamsters were compared with those from a previous pony challenge experiment. METHODS: Animals were immunised with inactivated vaccines containing one of 4 strains of equine influenza A H3N8 subtype virus isolated over a 26 year period (1963 to 1989), then challenged with a 1989 strain. RESULTS: Although there was no significant difference in titres of excreted virus between groups of vaccinated ponies, hamsters immunised with heterologous strains had significantly higher virus titres in the lung than hamsters vaccinated with the homologous strain. In both ponies and hamsters, the number of animals excreting virus was greater the earlier the isolation date of the vaccine strain, although this was only significant in the hamster study. CONCLUSIONS: Despite differences, the overall conclusion of both the pony and hamster models was that heterologous vaccines may be less effective than homologous vaccines at preventing virus excretion. POTENTIAL RELEVANCE: Further validation is required, but the hamster model shows potential for preliminary assessment of the effects of antigenic drift on vaccine efficacy.

Animals↗

PubMed2005

A model for pathogen population structure with cross-protection depending on the extent of overlap in antigenic variant repertoires.

The persistence of discrete antigenic types among pathogens with multiple immunogenic loci can be explained by the action of immune-mediated competition. It has previously been shown that pathogen populations will self-organize into non-overlapping subsets of antigenic variants if cross-protection between pathogen types sharing any variants is high. Here, we examine the critical question of whether such strain structure will emerge if the degree of immune-mediated competition is dependent on the number of variants shared between pathogen types, rather than in an all-or-nothing manner. Our analysis uncovers a progression from no strain structure through to discrete stable strain structure through intermediate partially structured states. This suggests that the number of loci or epitope regions required to detect linkage disequilibrium (as a manifestation of stable discrete strain structure) in pathogen populations correlates inversely with the strength of immune selection.

Antigenic Variation↗

PubMed1987

Expression of alfalfa mosaic virus coat protein gene confers cross-protection in transgenic tobacco and tomato plants.

A chimeric gene encoding the alfalfa mosaic virus (AlMV) coat protein was constructed and introduced into tobacco and tomato plants using Ti plasmid-derived plant transformation vectors. The progeny of the self-fertilized transgenic plants were significantly delayed in symptom development and in some cases completely escaped infection after inoculated with AlMV. The inoculated leaves of the transgenic plants had significantly reduced numbers of lesions and accumulated substantially lower amounts of coat protein due to virus replication than the control plants. These results show that high level expression of the chimeric viral coat protein gene confers protection against AlMV, which differs from other plant viruses in morphology, genome structure, gene expression strategy and early steps in viral replication. Based on our results with AlMV and those reported earlier for tobacco mosaic virus, it appears that genetically engineered cross-protection may be a general method for preventing viral disease in plants.

Journal Article↗

PubMed1988

Cross-protection by B subunit-whole cell cholera vaccine against diarrhea associated with heat-labile toxin-producing enterotoxigenic Escherichia coli: results of a large-scale field trial.

The B subunit (BS) of cholera toxin and that of the heat-labile enterotoxin (LT) of enterotoxigenic Escherichia coli (ETEC) are antigenically similar. We therefore assessed whether a combined cholera toxin BS/whole-cell (BS-WC) oral vaccine against cholera conferred cross-protection against LT-producing ETEC (LT-ETEC) diarrhea in a randomized, double-blind field trial among rural Bangladeshi children and women. The 24,770 persons who ingested two or more doses of BS-WC vaccine were compared with 24,842 controls who took two or more doses of killed whole-cell (WC) oral cholera vaccine. Sixty-seven percent fewer episodes of LT-ETEC diarrhea were noted in the BS-WC group than in the WC group during short-term (three-month) follow-up (P less than .01), but no reduction was evident during the ensuing nine months. Short-term protection was particularly notable against LT-ETEC diarrhea causing life-threatening dehydration (protective efficacy, 86%; P less than .05).

Adolescent↗

PubMed1984

Specific cross-protective antigonococcal immunity in the murine genital tract.

Specific acquired immunity to gonococci was studied in systemically immunized mice, challenged with 10(7) gonococci by intrauterine inoculation. Protection after intraperitoneal immunization was monitored by vaginal cultures taken 24 h post-challenge, since events during the first 24 h postexposure to gonococci are crucial in determining the outcome of infection. Mice were protected against gonococcal challenge by two inoculations with either live or boiled gonococci given 4 weeks apart, whereas immunization with one inoculation did not protect against challenge 1 week later. Protection was correlated with high titers of IgG antibody in serum after two immunizations, but not with the high titers of serum IgM antibody found after the one immunization. IgG antibodies, but not IgM antibodies, were shown to pass into genital secretions. Protection could be passively transferred by serum with high titers of antibody. Of most practical importance was the finding that not only were heat-stable antigens protective, but also heterologous protection resulted after immunization with three strains differing in source (disseminated gonococcal infection versus gonorrhea), opacity-transparency characteristics, and serum sensitivity. The data indicate that IgG antibodies resulting from systemic immunization with heat-stable antigens may be able to provide cross-protection immunity against gonorrhea.

Animals↗

PubMed2003

Cross-protection experiments with parasitoids in the genus Microplitis (Hymenoptera: Braconidae) suggest a high level of specificity in their associated bracoviruses.

The immunological and developmental effects of bracoviruses (BVs) from three parasitoids in the genus Microplitis (Braconidae: Microgastrinae) were compared in the hosts Pseudoplusia includens and Heliothis virescens (Lepidoptera: Noctuidae). Southern blotting experiments indicated that viral DNAs from Microplitis demolitor bracovirus (MdBV) cross-hybridized with viral DNAs from Microplitis croceipes bracovirus (McBV) and Microplitis mediator bracovirus (MmBV) under conditions of high stringency. Injection of calyx fluid plus venom from each parasitoid species dose-dependently delayed development of P. includens and H. virescens. Each virus also inhibited pupation of P. includens but not H. virescens. In situ hybridization experiments indicated that MdBV and McBV persistently infect hemocytes in both hosts while MmBV persistently infects hemocytes in P. includens but not H. virescens. While MdBV infection induced a loss of adhesion by most plasmatocytes, McBV and MmBV infection induced a loss of adhesion in less than 50% of cells. Cross-protection experiments indicated that calyx fluid plus venom from one species usually protected progeny of another species from encapsulation but did not always promote successful development.

Animals↗

PubMed1994

Cross-protective immunity induced by Babesia bovis clones with antigenically unrelated variable merozoite surface antigens.

Babesia bovis merozoite surface antigen 1 (MSA-1) induces antibodies capable of neutralizing merozoites in vitro. Both MSA-1 and the co-expressed MSA-2 are encoded by a polymorphic multigene family and are antigenically variant among strains isolated from widely separated geographic regions. In this study, cross-protective immunity between two B. bovis clones, Mexico Mo-7 and Israel-C, that have antigenically unrelated MSA-1 and MSA-2 surface proteins was assessed. Cattle immunized by infection with either clone were significantly protected against challenge with the uncloned Israel Bbv strain. This indicates that epitopes capable of inducing partial protection are shared among different strains and that immunity is not solely dependent upon MSA-1 or MSA-2. However, cattle immunized with the Israel-C clone, derived from the Israel Bbv strain, were significantly better protected against BbV challenge than were cattle immunized with the Mexico Mo-7 clone bearing antigenically unrelated MSA-1 and MSA-2. The significant difference in immunity induced by the homologous strain versus an antigenically variant strain indicates that epitope variation among strains is relevant to immunity against babesiosis.

Animals↗

PubMed1994

Responses to nutrient starvation in Pseudomonas putida KT2442: analysis of general cross-protection, cell shape, and macromolecular content.

The physiology of Pseudomonas putida KT2442 with respect to growth and carbon starvation was studied. During the transition from growth to nongrowth, the cell shape changes from cylindrical to spheric, a change which is accompanied by reductions in cell size, DNA and ribosome content, and the rate of total protein synthesis. In addition, a pattern of general cross-protection develops, which enables the cells to survive environmental stresses such as high and low temperatures, elevated osmolarity, solvents, and oxidative agents. Cultures are almost fully viable during 1 month of carbon, nitrogen, and multiple-nutrient starvation and are considered to be in an active nondormant state. In contrast, strain KT2442 does not survive well under conditions of sulfate and phosphate starvation.

Adaptation, Physiological↗

PubMed2004

Effects of amoxicillin subinhibitory concentrations on the cross-protection developed by pneumococcal antibodies in mouse sepsis caused by an amoxicillin-resistant serotype 6B Streptococcus pneumoniae strain.

A model of mouse sepsis caused by a serotype 6B Streptococcus pneumoniae strain (amoxicillin MIC of 8 microg/ml) was developed to investigate the therapeutic effect of an amoxicillin dose (3.12 mg/kg of body weight three times daily for 48 h) producing, over the whole treatment period, subinhibitory concentrations in serum (peak concentration [C(max)]: 6.1 microg/ml) in animals that prior to infection had been passively immunized with a 6B or 23F hyperimmune serum (obtained by immunization with a whole-cell heat-inactivated inoculum and diluted to produce no protective effect by itself). Mortality in nonimmunized animals treated with antibiotic (3.12 mg/kg) was 90%, and mortality in animals immunized but not treated with the antibiotic was 100%. Antibiotic treatment in immunized animals produced mortality rates </=20% when the hyperimmune serum was used, thus showing cross-protection and synergism (defined as the situation in which there is no response to the single agents [no differences versus placebo] while the combination exhibits significant activity) with subinhibitory concentrations of the antibiotic. The presence of antipneumococcal antibodies allowed antibiotic efficacy with negligible values of pharmacodynamic parameters (C(max)/MIC ratio of <1 and thus a null value for the time that serum levels exceed the MIC). This in vivo synergism offers a potential therapeutic strategy against resistant strains.

Amoxicillin↗

PubMed2000

Cross-protective murine graft-versus-leukemia responses to phenotypically distinct myeloid leukemia lines.

A c-myc retrovirus-transformed myeloid leukemia line, MMB3.19, of C57BL/6 (B6) origin, was developed to investigate graft-versus-leukemia (GVL) activity in murine bone marrow transplantation (BMT) models. It was previously determined that both naive and leukemia-presensitized CD4+-enriched T cells are capable of mediating GVL activity to MMB3.19 challenge in both syngeneic (B6) and allogeneic (C3H.SW-->B6) strain combinations, with the latter coinciding with minimal graft-versus-host disease. In the present study, MMB3.19 and 2 other similarly derived, yet phenotypically diverse, B6 myeloid leukemia lines (MMB1.10 and MMB2.18) were investigated for potential shared tumor antigens in the syngeneic GVL model. Morphologically, all 3 tumor lines are blastic with high cytoplasmic:nuclear ratios, but MMB2.18 displays dendritic processes, whereas MMB1.10 and MMB3.19 have a more rounded appearance. Flow cytometric analysis of the 3 lines revealed constitutive surface molecule expression of Mac-1, Mac-2, F4/80, LFA-1, B7-1, B7-2, H2Kb, H2Db, and macrophage scavenger receptor, consistent with macrophage/monocyte lineages. Furthermore, each of the lines expresses H2I-Ab, but to varying degrees, with MMB2.18 cells having the lowest percentage (31.6%). In vitro 51Cr release assays using MMB3.19-primed T-cell effectors demonstrated equivalent specific lysis of all 3 leukemia-line target cells. In addition, enzyme-linked immunospot analysis of MMB3.19-primed CD4+ T cells revealed significantly increased frequencies of tumor-stimulated interleukin (IL)-2-, IL-4-, and interferon-gamma-secreting cells when restimulated with each of the 3 leukemia lines. Furthermore, when MMB3.19-primed CD4+ T cells were administered in a BMT setting, a protective GVL effect was seen in those mice challenged with MMB1.10, MMB2.18, or MMB3.19. Therefore, in vitro and in vivo experiments indicate that the 3 distinct myeloid leukemia lines share 1 or more common major histocompatibility complex class II-restricted tumor antigens that can elicit a cross-protective in vivo T-cell GVL response.

Animals↗

PubMedDate not supplied

Active cross-protection induced by a recombinant baculovirus expressing chimeric infectious bursal disease virus structural proteins.

The VP2 structural gene encoded in the large genomic segment A of the variant GLS strain of infectious bursal disease virus (IBDV) was modified to encode a neutralization epitope (B69), found only on classic strains of IBDV. A chimeric cDNA clone of the large segment A, encoding VP3, VP4, and the modified variant IBDV VP2 structural proteins, was expressed in a recombinant baculovirus. The chimeric protein expressed was assessed with a panel of neutralizing monoclonal antibodies (MAbs), and it contained not only all previously MAb-defined GLS variant strain epitopes but also the B69 neutralization epitope found on classic IBDV strains. Complete active protection was afforded to specific-pathogen-free chickens by a subunit chimeric vaccine against virulent challenge with the classic IM and STC strains, as well as against the variant E/Del and GLS IBDV strains. Compared with a previously tested recombinant subunit vaccine, which incorporated unmodified baculovirus-expressed large-segment A GLS proteins, the recombinant chimeric subunit vaccine resulted in markedly improved active cross-protection against classic IBDV challenge.

Animals↗

PubMed2003

Cross-protective and infection-enhancing immunity in mice vaccinated against flaviviruses belonging to the Japanese encephalitis virus serocomplex.

The Japanese encephalitis virus serocomplex is a group of mosquito-borne flaviviruses that cause severe encephalitic disease in humans. The recent emergence of several members of this serocomplex in geographic regions where other closely related flaviviruses are endemic has raised urgent human health issues. Thus, the impact of vaccination against one of these neurotropic virus on the outcome of infection with a second, serologically related virus is unknown. We show here that immunity against Murray Valley encephalitis virus in vaccinated mice can cross-protect but also augment disease severity following challenge with Japanese encephalitis virus. Immunepotentiation of heterologous flavivirus disease was apparent in animals immunized with a 'killed' virus preparation when humoral antiviral immunity of low magnitude was elicited.

Adjuvants, Immunologic↗

PubMed1997

Cross-protection among lethal H5N2 influenza viruses induced by DNA vaccine to the hemagglutinin.

Inoculation of mice with hemagglutinin (HA)-expressing DNA affords reliable protection against lethal influenza virus infection, while in chickens the same strategy has yielded variable results. Here we show that gene gun delivery of DNA encoding an H5 HA protein confers complete immune protection to chickens challenged with lethal H5 viruses. In tests of the influence of promoter selection on vaccine efficacy, close correlations were obtained between immune responses and the dose of DNA administered, whether a cytomegalovirus (CMV) immediate-early promoter or a chicken beta-actin promoter was used. Perhaps most important, the HA-DNA vaccine conferred 95% cross-protection against challenge with lethal antigenic variants that differed from the primary antigen by 11 to 13% (HA1 amino acid sequence homology). Overall, the high levels of protection seen with gene gun delivery of HA-DNA were as good as, if not better than, those achieved with a conventional whole-virus vaccine, with fewer instances of morbidity and death. The absence of detectable antibody titers after primary immunization, together with the rapid appearance of high titers immediately after challenge, implicates efficient B-cell priming as the principal mechanism of DNA-mediated immune protection. Our results suggest that the efficacy of HA-DNA influenza virus vaccine in mice extends to chickens and probably to other avian species as well. Indeed, the H5 preparation we describe offers an attractive means to protect the domestic poultry industry in the United States from lethal H5N2 viruses, which continue to circulate in Mexico.

Animals↗

PubMed1999

Analysis of the Yersinia enterocolitica 0:8 V antigen for cross protectivity.

The plasmid encoded V antigen (Vag) of pathogenic Yersinia spp. is a major virulence factor as well as a protective immunogen. Recently, two main types of Vag, represented by either Yersinia enterocolitica 0:8 or Yersinia pseudotuberculosis, have been identified and it has been suggested, that antibodies generated against one type are unable to protect against Yersinia spp. carrying the other type. By using a recombinant Vag (rVagHis) of the Y. enterocolitica 0:8 type we show here, that actively immunized mice were completely protected against challenge with both, Y. enterocolitica 0:8 and Y. pseudotuberculosis serotype III. In addition, passive protection was possible with polyclonal rabbit anti-rVagHisIgG. However, while a single antibody dose (200 microgramg) was sufficient to protect against challenge with Y. enterocolitica 0:8, repetitive injections at intervals of 2 to 3 days were needed to protect against challenge with Y. pseudotuberculosis III. The apparent difference in protection correlated with a rapid disappearance of anti-rVagHisIgG from the circulation by days 3 to 4. The data therefore indicate, that expression of distinct types of Vag by Yersinia spp. does not necessarily exclude immunoprotection in mice immunized with the other type of Vag. It rather appears, that differences in immunoprotection between Yersinia species relate to the amount of cross-protective antibody. Finally, as revealed by the lack of complement-mediated killing and the lack of immunostaining of Yersiniae with anti-rVagHisantibodies, evidence is provided to indicate that immunoprotection does not occur via opsonisation or complement lysis.

Animals↗

PubMed2002

Analysis of serum cross-reactivity and cross-protection elicited by immunization with DNA vaccines against Streptococcus pneumoniae expressing PspA fragments from different clades.

Streptococcus pneumoniae is a major cause of disease, especially in developing countries, and cost-effective alternatives to the currently licensed vaccines are needed. We constructed DNA vaccines based on pneumococcal surface protein A (PspA), an antigen shown to induce protection against pneumococcal bacteremia. PspA fragments can be divided into three families, which can be subdivided into six clades, on the basis of PspA amino acid sequence divergence (S. K. Hollingshead, R. Becker, and D. E. Briles, Infect. Immun. 68:5889-5900, 2000). Since most clinical isolates belong to family 1 or family 2, PspA fragments from members of both of these families were analyzed. Vectors encoding the complete N-terminal regions of PspAs elicited significant humoral responses, and cross-reactivity was mainly restricted to the same family. DNA vaccines encoding fusions between PspA fragments from family 1 and family 2 were also constructed and were able to broaden the cross-reactivity, with induction of antibodies that showed reactions with members of both families. At least for the pneumococcal strains tested, the cross-reactivity of antibodies was not reflected in cross-protection. Animals immunized with DNA vaccines expressing the complete N-terminal regions of PspA fragments were protected only against intraperitoneal challenge with a strain expressing PspA from the same clade.

Animals↗

PubMed1988

Cross protection between a strain of Staphylococcus epidermidis and eight other species of coagulase-negative staphylococci.

Passive protective activity of rabbit antiserum prepared by a representative capsular type II strain of Staphylococcus epidermidis in mice was absorbed out with homologous capsular type strains of S. simulans, S. cohnii, S. xylosus, S. hominis, S. capitis, S. hyicus, S. haemolyticus, and S. saprophyticus in addition to the homologous strain. The minimum amount of the strains required for absorption differed greatly, depending upon the strain. No absorption of the activity was shown with a strain of capsular type I and III of S. epidermidis, S. simulans, and S. cohnii, and a strain of capsular type III of S. hominis. These results suggest a possible capsular type specificity in the cross protection between strains of S. epidermidis and other species of coagulase-negative staphylococci.

Animals↗

PubMedDate not supplied

A survey of non-specific cross-protective immunities induced by avian retroviruses.

Reticuloendotheliosis virus strain T (REV-T) induced immunity in chicks to challenge by representative subgroup members of the avian leukosis-sarcoma virus (ALSV) complex. Immunity levels were compared to determine the extent of antigenic relation between REV-T and the ALSV complex. Reciprocal studies using ALSV subgroup members and pheasant viruses as immunogens and REV-T as challenge were also performed. It was concluded that reciprocity of immunity is not equal between the viruses studied, nor is immunity directly related to the virus-neutralizing-antibody levels induced by immunization with the viruses studied. In some cases, the levels of cross-protection demonstrated may be a sign of the induction of antibodies to common or similar tumor-specific surface antigens rather than complete antigenic identity between REV-T and the ALSV members used; in others, virus-neutralizing antibodies may be a sign of partial identity between some proteins of REV-T and ALSV subgroup members.

Alpharetrovirus↗

PubMed2005

Cross-protective immunity in calves conferred by a DNA adenine methylase deficient Salmonellaenterica serovar Typhimurium vaccine.

The global trend towards intensive livestock production is associated with increased fecal oral pathogen transmission resulting in a high prevalence of Salmonella. Since many pathogenic Salmonella serovars are often endemic to livestock production systems, it is desirable to develop a vaccine that is capable of eliciting immunity to more than one serovar. Here we examined whether immunization with a modified live Salmonella enterica serovar Typhimurium vaccine strain lacking the DNA adenine methylase (Dam) conferred protection in calves against a heterologous S. enterica Dublin challenge. Vaccinated animals challenged with a virulent Dublin strain exhibited a significant attenuation of clinical disease (improved attitude scores and reduced fever and diarrhea) and a concomitant reduction in Dublin fecal shedding and colonization of mesenteric lymph nodes (MLN) compared to non-vaccinated control animals. These data suggest that vaccination with a dam(-) Typhimurium vaccine strain conferred significant cross-protection against clinical disease in cattle attributable to heterologous challenge with Dublin.

Animals↗