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PubMed1996

Protectotypic differentiation of avian infectious bronchitis viruses using an in vitro challenge model.

Two vaccine and three virulent strains of infectious bronchitis virus (IBV) were used to infect day-old specific-pathogen-free chickens. Precocious development of oviducts was induced in young female chicks by oestrogen injections. Tracheal and oviduct organ cultures prepared from immunised chickens were challenged in vitro with homologous and heterologous viruses to assess tracheal and oviduct cross-protection. Tracheal cross-protection was seen between serologically related and unrelated viruses. Protection at at the level of the oviducts was lower compared to that seen at the tracheal level. However, the yields of the homologous challenge viruses from immunised oviducts were significantly reduced as compared to yields from normal oviducts. After challenge, tracheal and oviduct ciliary scores were used to group the five strains of IBV into protectotypes. The five viruses could be grouped into three protectotypes and four serotypes. The virulent IBV strains were found to have caused complete stasis of oviduct cilia when examined at three weeks post-infection. Oestrogen treatment of chicks did not significantly alter the lymphocyte proliferation responses to concanavalin A or pokeweed mitogen. The applicability of this model for the study of protection afforded to the oviducts, in terms of protection against virus-induced damage, rather than drop in egg production, is discussed.

Animals↗

PubMed1992

Specific and non-specific mouse protection induced by different chemotypes of the Pseudomonas aeruginosa lipopolysaccharides.

Lipopolysaccharides (LPS) of Pseudomonas aeruginosa were studied by the mouse active, cross-protection test. The primary structure of O-specific polysaccharides (O-repeating units) of different chemotypes was determined and their cross-protective activity demonstrated. Low doses of LPS (0.1-1 micrograms) stimulated chemotype-specific protection against P. aeruginosa in mice. This immunity was associated with the primary structure of the LPS and it lasted for 14 days after the first or second immunization. High doses of LPS (10-100 micrograms) induced cross-protection against P. aeruginosa in mice. The cross-protective capacity was caused evidently by the secondary structure or conformation of LPS molecule, i.e. by the common conformational protective determinant. This cross-protection lasted for only 5 days after the first or second immunization.

Animals↗

PubMed1997

Vaccination and the population structure of antigenically diverse pathogens that exchange genetic material.

Populations of antigenically diverse pathogens undergoing genetic exchange may be categorized into strains on the basis of a set of principal protective antigens. The extent to which polyvalent vaccines based on these protective antigens can alter the population structure of the pathogen is determined by the degree of cross-protection between strains. In the case where there is no cross-protection, vaccinating against a particular strain will have no effect on the others. As cross-protection increases, the strains containing the antigenic variants included in the vaccine will be diminished in prevalence, and those that do not will increase in prevalence. The rise in prevalence of the latter will become more and more exaggerated as cross-protection increases. However, beyond a critical level of cross-protection, in the absence of vaccination, the steady state of the system is asymmetric in that a certain subset of strains (with non-overlapping repertoires of antigenic variants) will dominate over the others in terms of prevalence. Under these circumstances, a vaccine consisting of the most immunogenic combinations of antigenic variants can cause a dramatic increase in frequency of a subset of rare strains.

Alleles↗

PubMed1990

[Immunochemical properties of a protective cross-reacting antigen of meningococci].

The study of protective cross-reacting antigenic preparations isolated from meningococci of groups A and C in the blot immunoassay has shown the presence of a group of proteins with a molecular weight ranging from 23 to 31 KD and common for 8 tested serological groups of meningococci, gonococci and 4 nonpathogenic Neisseria species. The possible role of these structures as common Neisseria antigen in the formation of natural resistance to meningococcal infection is discussed.

Antigens, Bacterial↗

PubMed1989

P-fimbriae vaccines. II. Cross reactive protection against pyelonephritis.

Protection against acute pyelonephritis was induced by immunization of baboons with purified P-fimbriae of Escherichia coli as vaccines. To test for cross-protective capacity of two different P-fimbriae vaccines we vaccinated baboons with P-fimbriae purified from either E. coli strain ER2 or strain JR1 and subsequently challenged the animals with E. coli strain JR1. All vaccinated animals showed elevated antibody titers to P-fimbriae from both of the E. coli strains used. Both vaccines tended to reduce the time of bacteriuria. They partially prevented pyelonephritis and protected against loss of renal function.

Animals↗

PubMed2003

Regions of PspA/EF3296 best able to elicit protection against Streptococcus pneumoniae in a murine infection model.

Pneumococcal surface protein A (PspA) can elicit protection against Streptococcus pneumoniae in mouse infection models. PspA is classified by serology and amino acid sequence into two major families that are divided by sequence into five clades. The most variable portion of the molecule is the alpha-helical domain, which comprises the N-terminal half of PspA. Prior studies of a family 1 PspA protein observed that protective antibodies are reactive with epitopes in the alpha-helical domain and that most cross-protective epitopes mapped to the 108 most C-terminal amino acids of the alpha-helical region. In these studies, we have used six overlapping recombinant fragments of family 2, clade 3 PspA/EF3296 to map the protection-eliciting regions of its alpha-helical domain. The three fragments, which included the 104 most C-terminal amino acids of the alpha-helical domain (314 to 418), could each elicit protection against EF3296. A fragment comprising amino acids 75 to 305 failed to elicit significant protection. A fragment containing amino acids 1 to 115 elicited protection against EF3296 in BALB/c mice but not in CBA/N mice. All three fragments containing amino acids 314 to 418 were able to elicit cross-protection against pneumococci expressing PspA proteins of clades 2, 3, 4, and 5. Cross-protection elicited by these three fragments was easier to demonstrate in CBA/N mice than in BALB/c mice. The 1-to-115 fragment, however, elicited some cross-protection against clades 2 and 4 in BALB/c mice but not in CBA/N mice. These studies provide support for the importance of the C-terminal 104 and N-terminal 115 amino acids of the alpha-helical region of PspA in the elicitation of cross-protection.

Animals↗

PubMed2006

[Intranasal inactivated influenza vaccine].

Natural influenza virus infection is well known to be superior to parenteral inactivated vaccines, which induce serum IgG antibodies(Abs) alone, in inducing the broad-spectrum cross-protection against variant virus infection. Secretory IgA Abs, which provide cross-protection strongly against infection with variant viruses within the same subtype mainly in the upper respiratory tract, serum IgG Abs, which provide cross-protection weakly against infection with variant viruses mainly in the lower respiratory tract, and cytotoxic T lymphocytes, which provide cross-protection against infection with different subtype viruses and whose role is not always big in humans, are involved in the defence mechanisms induced by natural infection. The development of intranasal inactivated vaccine, capable of inducing both IgA and IgG Abs, is important to improve the efficacy of current inactivated vaccine.

Adjuvants, Immunologic↗

PubMed2001

Cross-strain protection against clinical and laboratory strains of Pseudomonas aeruginosa mediated by dendritic cells genetically modified to express CD40 ligand and pulsed with specific strains of Pseudomonas aeruginosa.

We have shown that dendritic cells (DCs) genetically engineered with a recombinant adenovirus vector (Ad) to express CD40 ligand (CD40L) elicit specific humoral immunity against the Pseudomonas aeruginosa laboratory strain PAO1, without CD4(+) T cell help. In the present study, using several different strains of P. aeruginosa, we examine whether this strategy is generally applicable to enhancing clinically relevant pathogen-specific immunity. Mice immunized with DCs modified with CD40L and pulsed with heat-killed P. aeruginosa clinical strain PA514, originally isolated from the sputum of an individual with cystic fibrosis, survived lethal respiratory challenge with PA514-impregnated agar beads. Consistent with this effective in vivo protection, the immunized mice generated high levels of serum isotype-switched antibodies directed against PA514 without concomitant nonspecific elevations of total serum immunoglobulin levels. The CD40L genetically engineered DCs pulsed with seven of eight different strains of P. aeruginosa afforded significant, albeit variable, cross-protection against lethal respiratory challenge with a clinical (PA514) or laboratory (PAO1) strain of P. aeruginosa. CD40L genetically modified DCs pulsed with a clinical (PA514) or laboratory (PAO1) strain of P. aeruginosa initiated cross-reacting antibody responses against each other, but not against Escherichia coli and vice versa. These observations may be useful in developing vaccines for infectious diseases, including P. aeruginosa infection.

Adenoviridae↗

PubMed2000

Efficacy of an outer membrane protein of Pasteurella haemolytica A2, A7 or A9-enriched vaccine against intratracheal challenge exposure in sheep.

The outer membrane proteins (OMP) were extracted from the P. haemolytica A2, A7 and A9 to determine their potential as immunogens and their capability for cross-protection. Sixty lambs of approximately 9 months old were divided into four main groups. Animals in Group 1 were vaccinated with 2ml vaccine containing 100microg/ml of the outer membrane proteins of P. haemolytica A2. Animals in Group 2 were similarly vaccinated with the OMPs of P. haemolytica A7 while Group 3 with OMPs of P. haemolytica A9. Animals in Group 4 were unvaccinated control. During the course of the study, serum was collected to evaluate the antibody levels toward each OMP. There appeared to be good immune responses. However, high antibody levels did not necessarily result in good protection of the animals, particularly against cross-infection with P. haemolytica A9 in animals vaccinated with the OMPs of P. haemolytica A2. It seemed that the antibody responses were more specific toward the homologous challenge but generally did not cross-protect against heterologous serotype challenge. However, the OMPs of P. haemolytica A7 produced good in vivo cross-protection and excellent correlations when good antibody responses against all serotypes led to successful reductions of the extent of lung lesions following homologous and heterologous challenge exposures. Thus, the OMPs of P. haemolytica A7 was effective in protecting animals against homologous and heterologous infection by live P. haemolytica A2, A7 and A9.

Animals↗

PubMed1986

Immunotherapy of gram-negative bacterial sepsis. A single murine monoclonal antibody provides cross-genera protection.

Previous experimental and clinical studies have demonstrated the ability of polyclonal antibody directed against the core lipopolysaccharide (LPS)-lipid A component of endotoxin to reduce mortality. We sought to characterize the ability of a single murine monoclonal IgG1 antibody (8A1 MAb) to react to a variety of gram-negative microorganisms, to promote phagocytosis, and to provide protection during experimental murine sepsis. The 8A1 MAb reacted to various gram-negative bacterial whole cell and LPS antigens examined by enzyme-linked immunosorbent assay. Reactivity was highest to Salmonella minnesota Re LPS and lipid A. Phagocytosis was promoted by this monoclonal antibody to several gram-negative bacteria, except Pseudomonas aeruginosa. The 8A1 MAb (2 mg per mouse) enhanced survival during bacteremia due to either Escherichia coli 0111:B4 or Klebsiella pneumoniae, and during endotoxemia due to all types of LPS examined except P aeruginosa. We concluded that a single MAb with anti-lipid A specificity was cross reactive in vitro and cross protective in vivo. A clinical trial comparing polyclonal and monoclonal antibody in high-risk septic patients seems warranted.

Animals↗

PubMed1994

Satellite tobacco mosaic virus sequence variants with only five nucleotide differences can interfere with each other in a cross protection-like phenomenon in plants.

The type strain of satellite tobacco mosaic virus (STMV) contains two major variants, designated type 5 (T5) and type 6 (T6), which can be easily distinguished by RNase protection analyses. Clones containing cDNA of representative T5 and T6 STMV genomes have only five single-base differences in the entire 1059-nucleotide genome, and RNA transcribed from each clone is highly infectious when inoculated onto tobacco plants. The different RNase protection assay patterns can be used as genetic markers to identify individual STMV variants and to follow the interactions of variants and their progeny during coinfections in plants. The study described here investigated the effects of coinoculation and various delayed inoculations of T5 and T6 variants on the composition of the progeny STMV populations in systemically infected tobacco tissues. When T5 and T6 STMV RNAs were coinoculated or inoculated with 1-hr delays, the progeny from individual plants most often contained a mixture of T5 and T6 genomes. However, when there was a 24-hr delay between inoculations, the balance of T5 and T6 components in the progeny populations shifted toward predominance of the first variant inoculated. With delays of 3 or 7 days only the first variant was evident in the progeny populations, indicating that established replication of one STMV variant interferes with replication of another in a manner similar to the cross protection phenomenon.

Helper Viruses↗

PubMed1990

Colonisation by Pasteurella multocida in atrophic rhinitis of pigs and immunity to the osteolytic toxin.

Gnotobiotic pig antisera to purified toxoid from a capsule type A or D strain of Pasteurella multocida contained large quantities of antitoxin but comparatively little antibody to a crude lysate of P. multocida. These sera given intraperitoneally to further pigs were almost completely protective against turbinate atrophy after intranasal inoculation of dilute acetic acid and infection with type D toxigenic P. multocida. In contrast, antisera to a crude lysate or bacterin of toxigenic P. multocida which contained large titres of antibody to P. multocida lysate, but no detectable antitoxin, were not protective. Colonisation by toxigenic P. multocida was significantly reduced in protected pigs and was similar to colonisation by nontoxigenic P. multocida in pigs untreated or treated with dilute acetic acid. These results indicated (1) that antitoxin was protective and cross protective between toxins from different capsule types; and (2) that the toxin was the main colonisation factor produced by toxigenic bacteria in the acetic acid model of infection and that immunity to it did not eliminate infection.

Animals↗

PubMedDate not supplied

Vaccination against schistosomiasis and fascioliasis with the new recombinant antigen Sm14: potential basis of a multi-valent anti-helminth vaccine?

Molecular cloning of components of protective antigenic preparations have suggested that related parasite fatty acid binding proteins could form the basis of the well documented protective, immune cross reactivity between the parasitic trematode worms Fasciola hepatica and Schistosoma mansoni. We have now confirmed the cross protective potential of parasite fatty acid binding proteins and suggest that it may be possible to produce a single vaccine that would be effective against at least two parasites, F. hepatica and S. mansoni of veterinary and human importance respectively.

Animals↗

PubMed2004

Defense mechanisms against influenza virus infection in the respiratory tract mucosa.

The respiratory tract mucosa is not only the site of infection for influenza viruses but also the site of defense against virus infection. Viruses are initially detected and destroyed non-specifically by innate immune mechanisms, but if the viruses escape the early defense mechanisms, they are detected and eliminated specifically by adaptive immune mechanisms. The major adaptive immune mechanisms are as follows. (i) Specific secretory-IgA (S-IgA) antibodies (Abs) and CTLs (CD8+ cytotoxic T lymphocytes) are involved in the recovery from influenza following viral infection of naive mice. (ii) Preexisting specific S-IgA and IgG Abs in the immunized animals are involved in viral elimination by forming virus-Ig complexes shortly after re-infection. By their polymeric nature, the S-IgA Abs, which are carried to the mucus by transepithelial transport used for dimeric IgA (dIgA) Abs, provide not only protection against homologous virus infection but also cross-protection against drift virus infection. The IgG Abs, which transude from the serum to the mucus by diffusion, provide protection against homologous virus infection. They are largely distributed on the alveolar epithelia to prevent influenza pneumonia. (iii) In the absence of Abs in the pre-immunized animals, the production of specific IgA and IgG Abs by B memory cells is accelerated after re-infection, and these antibodies play a role in viral elimination from day 3 onwards after re-infection. (iv) In epithelial cells of infected animals, specific dIgA Abs being trafficked through the epithelial cells may be involved in the prevention of viral assembly by binding to newly synthesized viral proteins. (v) In the pre-immunized animals, CTL production by memory T cells is also accelerated and these cells appear to participate in the killing of the host cells infected with different subtype viruses (within the same type) from day 3 onwards after re-infection. (vi) Similarly, memory Th1 cells that mediate an accelerated delayed-type hypersensitivity response are involved in blockade of virus replication by secreting IFN-gamma in mice challenged with different subtype viruses. These defense mechanisms suggest that the development of a mucosal vaccine, capable of inducing S-IgA Abs, which provide cross-protection against variant viruses within the same subtype, serum IgG Abs to prevent lethal influenza pneumonia and CTLs, which provide broad cross-protection against different subtype viruses, is strategically important to control influenza.

Animals↗

PubMed1980

Further studies on caprine and ovine mycoplasmas related to Mycoplasma mycoides subsp. mycoides.

Nine caprine and ovine mycoplasma strains, said to be indistinguishable serologically from Mycoplasma mycoides subsp. mycoides (the causative organism of contagious bovine pleuropneumonia; CBPP) were examined in mice by (1) a mycoplasmaemia test, and (2) a cross-protection test. Of the nine strains, two from goats belonged to a small colony (SC) type; four caprine and three ovine strains belonged to a large colony (LC) type.The two SC strains - like a single SC strain examined in an earlier study - were indistinguishable from genuine M. mycoides subsp. mycoides as isolated from CBPP. They produced mycoplasmaemia readily. In a cross-protection test, the two SC strains and a CBPP strain immunized completely against each other.Of the seven LC strains, six - like six LC strains examined in an earlier study - were easily distinguished from genuine M. mycoides subsp. mycoides; except for one that was not tested, all were shown to lack the ability to produce mycoplasmaemia readily. In cross-protection tests all six strains immunized partially but not completely against a CBPP strain.The seventh LC strain (Mankefår 2833) was exceptional: it produced mycoplasmaemia readily, resembling the SC strains in this respect. Like other LC strains, in cross-protection tests it protected only partially against a CBPP strain. Strain Mankefår 2833 was isolated in ca. 1965 by Brack from a Barbary sheep (Ammotragus lervia) in a German zoo.The ability of Mankefår 2833 to produce mycoplasmaemia enabled it to be used as a challenge strain in cross-protection tests. For the purpose of such tests the collection of nine mycoplasma strains referred to above was augmented with six LC strains from an earlier study. Partial but not complete protection against Mankefår 2833 was produced by two caprine SC strains, one CBPP strain, and nine LC strains. Three further LC strains gave protection that may have been as strong as that produced by the homologous strain, but confirmatory experiments are needed. A strain of M. mycoides subsp. capri gave no protection against Mankefår 2833.

Animals↗

PubMed2005

CD8+ T-cell-mediated cross-clade protection in the genital tract following intranasal immunization with inactivated human immunodeficiency virus antigen plus CpG oligodeoxynucleotides.

Human immunodeficiency virus (HIV) is a mucosally transmitted infection that rapidly targets and depletes CD4+ T cells in mucosal tissues and establishes a major reservoir for viral persistence in gut-associated lymphoid tissues. Therefore, vaccines designed to prevent HIV infections must induce potent and durable mucosal immune responses, especially in the genital tract. Here we investigated whether intranasal (i.n.) immunization with inactivated gp120-depleted HIV-1 antigen (Ag) plus CpG oligodeoxynucleotide (ODN) as an adjuvant induced local immune responses in the genital tract and cross-clade protection against intravaginal (IVAG) challenge. Lymphocytes isolated from the iliac lymph nodes (ILNs) and genital tracts of female mice i.n. immunized with HIV-1 Ag plus CpG showed significant HIV-specific proliferation and produced significantly higher levels of gamma interferon (IFN-gamma) and beta-chemokines than mice immunized with HIV-1 Ag alone or mixed with non-CpG ODN. CD8+ lymphocytes were dramatically increased in the genital tracts of mice immunized with HIV-1 Ag plus CpG, and protection following IVAG challenge with recombinant vaccinia viruses (rVVs) expressing HIV-1 gag was shown to be CD8 dependent. Finally, cross-clade protection was observed between clades A, C, and G but not B following IVAG challenge with rVVs expressing HIV-1 gag from different clades. These studies provide evidence that mucosal (i.n.) immunization induced strong local T-cell-mediated immune responses in the genital tract and cross-clade protection against IVAG challenge.

AIDS Vaccines↗

PubMed1984

A study of F38-type and related mycoplasmas by mycoplasmaemia and cross-immunization tests in mice.

In vivo methods were used to study the F38-type mycoplasma in parallel with related mycoplasmas. Three of five strains of 'bovine serogroup 7' with an unknown history of subculture produced mycoplasmaemia in mice inoculated intraperitoneally. A strain of 'bovine serogroup L' also produced mycoplasmaemia, but no evidence of similar ability could be found for single strains of Mycoplasma capricolum, M. equigenitalium and M. primatum, or for two strains of the F38-type mycoplasma. In cross-immunization tests a bovine serogroup 7 strain (NCTC 10133) and a strain ('Blenheim') of the SC (small colony) type of M. mycoides subsp. mycoides were used for the purpose of challenge. Cross-protection was described as 'complete' or 'partial', depending on whether it was as great as, or less than, that produced by homologous vaccine. Although strain NCTC 10133 protected strongly, possibly completely, against Blenheim, and Blenheim gave partial protection against NCTC 10133, challenge with NCTC 10133 and Blenheim gave strikingly different results. Thus (1) F38-type strains, M equigenitalium and M. primatum all gave partial cross-protection against NCTC 10133 but not against Blenheim, (2) NCTC 10133, unlike Blenheim, was seldom susceptible to partial cross-protection by LC (large colony) strains of M. mycoides subsp. mycoides, and (3) three SC strains - which would have protected completely against Blenheim - protected only partially against NCTC 10133. NCTC 10133 and Blenheim were similar, however, in that M. capricolum and M. mycoides subsp. capri failed to cross-protect against them both.

Animals↗

PubMed1994

Coat protein-mediated resistance in transgenic plants.

This review describes the proposed mechanism(s) of classical virus cross-protection in plants, followed by those suggested for coat protein-mediated resistance (CP-mediated resistance). Although both have common features, cross-protection is thought to be a complex response caused by the replication and expression of the entire viral genome, whereas the resistance conferred by the expression of a virus coat protein gene is more limited. The term genetically engineered cross-protection is frequently used because in many cases the phenotype of resistance mimics that of cross-protection. However, CP-mediated resistance, although a narrow term, more accurately describes the resistance that results from the expression of a virus CP gene in transgenic plants.

Capsid↗