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Cross-protection against microvariants of influenza virus type B by vaccinia viruses expressing haemagglutinins from egg- or MDCK cell-derived subpopulations of influenza virus type B/England/222/82.

B/Singapore/222/79-like influenza viruses isolated from three patients during the winter of 1981 to 1982 and cultured in either embryonated hens' eggs or MDCK cells were studied. Sequence analysis indicated that the haemagglutinin (HA) genes of the six virus preparations contained at least four distinct HA1 sequences which differed by up to six amino acids. Only one pair of viruses had amino acid differences between the egg- and MDCK cell-derived viral subpopulations and this change did not affect a glycosylation site. Mice infected with previously described recombinant vaccinia viruses expressing either the egg- or MDCK cell-derived HA of B/England/222/82 developed neutralizing antibodies against all of the 1982 type B viruses and were protected against intranasal challenge with these viruses. Therefore, in this model system, the minor sequence variation between the HAs of egg- and MDCK cell-derived influenza B/England/222/82 virus had no detectable effect on the induction of cross-protection.

Amino Acid Sequence↗

Coronavirus infections in the laboratory rat: degree of cross protection following immunization with a heterologous strain.

One hundred and twenty-one specific pathogen-free male Wistar rats eight to ten weeks of age were used to evaluate the efficacy of Parker's rat coronavirus (PRC) in affording cross protection on subsequent challenge with virulent sialodacryoadenitis (SDA) virus. Sixty-two animals were inoculated intranasally on day 0 and 21 days later with approximately 10(2) median tissue culture infective doses (TCID50) of the tenth passage of PRC replicated in L-2 cells. Animals were selected at random postvaccination to evaluate the safety and efficacy of PRC by histopathology, immunohistochemistry and serology. At three and six months postvaccination (PV), vaccinated and seronegative control rats were inoculated intranasally with approximately 10(3) TCID50 doses of virulent SDA virus. Challenged rats were then killed at 6, 10 and 14 days postchallenge and necropsied. Evaluations were based on lesion indices in lacrimal and salivary glands and respiratory tract, the presence of viral antigen by immunohistochemistry, and antibody response. Lesions were observed in rats killed PV, but in general, they were significantly reduced compared with those present in seronegative animals post-exposure to virulent SDA virus (p < or = 0.05). However, they were still considered to be an unacceptable level for a routine vaccination procedure. Potvaccination antibody titers to rat coronavirus were evident in all animals tested at three or six months prior to challenge with SDA virus.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗

A comparison of cross protection between BCG, Hammondia hammondi, Besnoitia jellisoni and Toxoplasma gondii in hamsters.

The effect of pretreatment with BCG strain of Mycobacterium tuberculosis or Hammondia hammondi 21 days before challenge with lethal doses of T oxoplasma gondii and Besnoitia jellisoni was studied in hamsters. The results indicated that the intracardial administration of BCG provided no protection against either T. gondii or B. jellisoni. The hamsters immunized with H. hammondi survived challenge with 10(4) lethal doses of T. gondii but only 1 lethal dose with B. jellisoni, indicating strong cross protection between H. hammondi and T. gondii and only a marginal one between H. hammondi and B. jellisoni.

Animals↗

The mechanism of cross-protection afforded by dengue virus against West Nile virus in hamsters.

The protection afforded by similar concentrations of different dengue virus serotypes against a subsequent challenge of West Nile virus was studied in hamsters. The New Guinea C strain of dengue 2 virus gave the best protection. It was found that the anamnestic neutralizing antibody response induced by the challenge West Nile virus against West Nile virus in hamsters, previously immunized with dengue 2 virus, might play a major role in the cross-protection observed in this system.

Animals↗

Identification of group B streptococcal Sip protein, which elicits cross-protective immunity.

A protein of group B streptococci (GBS), named Sip for surface immunogenic protein, which is distinct from previously described surface proteins, was identified after immunological screening of a genomic library. Immunoblots using a Sip-specific monoclonal antibody indicated that a protein band with an approximate molecular mass of 53 kDa which did not vary in size was present in every GBS strain tested. Representatives of all nine GBS serotypes were included in the panel of strains. Cloning and sequencing of the sip gene revealed an open reading frame of 1,305 nucleotides coding for a polypeptide of 434 amino acid residues, with a calculated pI of 6. 84 and molecular mass of 45.5 kDa. Comparison of the nucleotide sequences from six different strains confirmed with 98% identity that the sip gene is highly conserved among GBS isolates. N-terminal amino acid sequencing also indicated the presence of a 25-amino-acid signal peptide which is cleaved in the mature protein. More importantly, immunization with the recombinant Sip protein efficiently protected CD-1 mice against deadly challenges with six GBS strains of serotypes Ia/c, Ib, II/R, III, V, and VI. The data presented in this study suggest that this highly conserved protein induces cross-protective immunity against GBS infections and emphasize its potential as a universal vaccine candidate.

Amino Acid Sequence↗

Cross-protection against challenge by intravenous Escherichia coli verocytotoxin 1 (VT1) in rabbits immunized with VT2 toxoid.

Rabbits challenged intravenously with Escherichia coli verocytotoxin (VT1, Shiga toxin 1, Stx1) die after developing diarrhea and paralysis, and this outcome can be prevented by pre-immunization with VT1 toxoid. In nonimmune rabbits, intravenously administered 125I-VT1 binds to the central nervous system and gastrointestinal tract, whereas in immunized animals, these organs are spared and the toxin localizes in the liver and spleen. In rabbits immunized with either VT1 or VT2 toxoids, both the homologous or heterologous toxins are prevented from binding to target organs. This has lead to the advancement of a hypothesis that cross-protection in vivo can be induced to both toxins by immunization with a toxoid even though these toxins do not exhibit cross-neutralization in vitro. It was shown that rabbits immunized with VT2 were fully protected from the intravenous administration of 10 LD50 and 50 LD50 of VT1, and this correlated directly with the protection from binding of this toxin to target organs. These findings have important implications on the design of the vaccination strategies to prevent human VT-mediated diseases and also validate the concept of testing for immunity to VT by monitoring the inhibition of binding of the 125I-VT to target organs in preference to performing LD50 assays.

Animals↗

Prevention of tumors in rats by cross-protective immunization.

F344 inbred were repeatedly immunized (days 0, 28, and 42) with normal syngeneic or allogeneic rat tissues or transplantable syngeneic or allogeneic rat tumors (some of which were virus producing). Immunized rats were challenged by sc injection of 10(5) or 10(6) syngeneic rat tumor cells from either of two different tumor lines. Successful cross-protective immunization prevented tumor development in rats that were challenged at 100-1,000 times the 50% tumor dose. The protection was essentially lifelong and complete in that no tumors appeared up to 200 days post challenge in some experiments. To be successful, the tumor cell vaccines had to express a complement-fixing cross-reacting antigen detected with sera from rats bearing any of several different tumors and to be able to induce a spontaneously regressing tumor in the host.

Animals↗

Cross-protection by anti-core glycolipid antibodies: evidence from animal experiments.

The ability of antibodies against the core glycolipid (CGL) of endotoxin to protect experimentally infected animals against death from Gram-negative sepsis is reviewed. The limitations and confounding factors inherent to animal models of sepsis are also briefly discussed. This review considers 30 studies in mice and 12 in other animal species that investigated protection against heterologous challenge by passive immunization with anti-CGL antibodies. In 28 (67%) of the reviewed studies antibodies were found to be protective, either prophylactically (n = 17) or therapeutically (n = 11). With the possible exception of the type of antibody preparation that was used (monoclonal versus polyclonal antibodies), none of the many differences in the experimental protocols were clearly correlated with success. Convincing proof is still lacking for any of the hypothetical mechanisms of protection by anti-CGL antibodies. Moreover, the evidence that protection by these antibodies is attributable to their anti-CGL specificity is poor. The available data raise serious questions about the validity of the concept underlying the search for broadly cross-protective antibodies raised against the core region of endotoxin. However, continuing research suggests that endotoxin still is a valid target in devising new adjunctive treatment strategies to improve the outcome of serious Gram-negative infections.

Animals↗

Analogous cytokine responses to Burkholderia pseudomallei strains contrasting in virulence correlate with partial cross-protection in immunized mice.

Cytokine mRNA levels were assessed in Burkholderia pseudomallei-susceptible BALB/c mice and B. pseudomallei-resistant C57BL/6 mice following administration of a sublethal dose of less virulent (LV) B. pseudomallei, a candidate immunogen tested for protection against a highly virulent (HV) challenge. Compared on the basis of the bacterial loads, the cytokine patterns induced by HV and LV B. pseudomallei were similar, involving gamma interferon, interleukin-10, and other cytokines. Partial cross-protection between B. pseudomallei strains is shown to be associated with cytokine profiles involving both type 1 and type 2 cytokines.

Animals↗

Human anti-Pseudomonas aeruginosa outer membrane proteins IgG cross-protective against infection with heterologous immunotype strains of P. aeruginosa.

In order to develop an effective means to treat and prevent Pseudomonas aeruginosa infections, we have purified P. aeruginosa outer membrane protein (Oprs)-specific human IgG antibody using a large-scale affinity column. In this study, we investigated the cross-protective activity of the purified anti-Oprs IgG against various immunotype strains of P. aeruginosa. The anti-Oprs IgG reacted with Oprs isolated from seven Fisher-Devlin immunotype strains of P. aeruginosa and was able to promote opsonophagocytic killing of all seven immunotype strains by human phagocytic cells. Administration of 500 microg anti-Oprs IgG to mice raised the LD50 of the P. aeruginosa strains by 8-250-fold, indicating the protective capacity against heterologous P. aeruginosa strains as well as homologous strains. In contrast, despite high titers against P. (aeruginosa Oprs, total serum IgG isolated from burn patient sera was no better than normal serum IgG in protecting mice from infection with P. aeruginosa. These data demonstrate that the affinity-purified human anti-Oprs IgG could afford protection against heterologous immunotype P. aeruginosa strains and provide a rationale to use anti-Oprs IgG as an adjunct for treatment of P. aeruginosa infections in humans.

Animals↗

Cross-protection against mucosal simian immunodeficiency virus (SIVsm) challenge in human immunodeficiency virus type 2-vaccinated cynomolgus monkeys.

In this study we compared the efficacy of live attenuated human immunodeficiency virus type 2 (HIV-2) vaccine alone versus boosting with live non-pathogenic HIV-2 following priming with ALVAC HIV-2 (recombinant canarypox virus expressing HIV-2 env, gag and pol). Six monkeys were first inoculated intravenously with live HIV-2(SBL-6669) and 7 to 10 months later were challenged intrarectally with 10 MID(50) of cell-free simian immunodeficiency virus (SIV) strain SIVsm. One monkey was completely protected against SIV infection and all five monkeys that became SIV-infected showed a lower virus replication and an initial lower virus load as compared with a parallel group of six control animals. In another experiment five monkeys were immunized either three times with ALVAC HIV-2 alone or twice with ALVAC HIV-2 and once with purified native HIV-2 gp125. The monkeys were then challenged with HIV-2 given intravenously and finally with pathogenic SIVsm given intrarectally. After challenge with SIVsm, three of five monkeys were completely protected against SIVsm infection whereas the remaining two macaques became SIV-infected but with limited virus replication. In conclusion, vaccination with an ALVAC HIV-2 vaccine followed by exposure to live HIV-2 could induce cross-protection against mucosal infection with SIVsm and seemed to be more efficient than immunization with a live HIV-2 vaccine only.

AIDS Vaccines↗

Cross-protective immunity to Gram-negative bacilli: studies with core glycolipid of Salmonella minnesota and antigens of Streptococcus pneumoniae.

Two immunoprophylactic approaches to the control of infections caused by gramnegative bacilli were evaluated by study of experimental infections in animals. The core glycolipid antigen derived from the Re mutant of Salmonella minnesota R595 is shared by virtually all enteric bacteria, and immunization with this endotoxin protects against the hemodynamic sequelae of bacterial infection and pyrexia without enhancing intravascular clearance of bacteria. The degree of protection afforded by active and passive immunization with core glycolipid was significantly less than that conferred by type-specific immunization. Escherichia coli and Klebsiella pneumoniae share capsular antigens with some strains of Streptococcus pneumoniae; by the mechanism of enhanced opsonization, antibodies to S. pneumoniae may cross-protect against infection with E. coli or K. pneumoniae.

Animals↗

Chemical modulation of physiological adaptation and cross-protective responses against oxidative stress in soil bacterium and phytopathogen, Xanthomonas.

Soil bacteria need to adapt quickly to changes in the environmental conditions. Physiological adaptation plays an important role in microbial survival, especially under stressful conditions. Here the abilities of chemicals and pesticides to modulate physiological adaptive and cross-protective responses, that make the bacteria more resistant to oxidative stress, are examined in the soil bacterium and phytopathogen, Xanthomonas. The genetic basis for the observed stress resistance, as well as the regulatory mechanisms controlling gene expression during the process, has begun to be elucidated.

Adaptation, Physiological↗

[The Borrelia of ornithodoros in tropical Africa: value and limits of cross protection tests in the mouse].

The identification of Borrelia strains isolated from ticks or relapsing fever patients is not easy. Seizing the opportunity of recent isolation of such strains from Western Africa, we tried to evaluate the interest and the limits of a method classically proposed for that aim; cross protection test in mouse. This technique is proving rather difficult to perform because of different technical reasons; the results are critical to read. In some cases, these results seem undeniable, but the observed differences in protection levels are often weak, inconstant, insufficiently reliable to constitute a diagnostic tool. So it appears important to develop other identification methods, based on molecular analysis of Borrelia DNA, which will be more subtle and more specific.

Africa, Western↗

Cross-protective antigens of Neisseria meningitidis obtained from Slaterus group Y.

An extraction of the cells of Neisseria meningitidis serogroup Y with an aqueous solution of calcium choride (0.9 m) has been shown to solubilize a number of antigens. By immunodiffusion, this mixture of antigens has been shown to react with its group-specific antiserum and also to cross-react with a number of other group-specific antisera. The cross-reacting antigen appears to be an antigen common to a number of other serogroups of meningococci, and there is some evidence that it is protein in nature. It has been demonstrated further that the calcium chloride extract contains a strong cross-protective antigen, as shown by its ability to provide good, active immunity in mice to both the homologous and heterologous serogroups of meningococci.

Animals↗

Cross-protection of mice against a global spectrum of rabies virus variants.

Rabies, a continuing worldwide problem, kills tens of thousands of people and millions of animals each year. The problem is most severe in developing countries, where cell culture-derived vaccines are unaffordable and the available nervous tissue-derived vaccines are often of questionable immunogenicity and may produce neurological complications. To determine the feasibility of developing a vaccine with worldwide applicability, we investigated whether recombinant vaccinia viruses expressing either the glycoprotein (G), the nucleoprotein (N), or both the G and N (GN) of the challenge virus strain (CVS) of rabies virus would cross-protect mice against 17 rabies virus isolates representing the spectrum of rabies virus variants found worldwide. The results were compared with the commercially available human diploid cell vaccine (HDCV). Among mice injected with any of the 17 viruses, > or = 95% were protected by vaccination with recombinant viruses expressing G or GN, and > or = 85% of the mice were protected by the HDCV. The recombinant virus expressing N was less protective, protecting against only 11 of the 17 viruses. Antibody prepared against the G of the strains used in the vaccines neutralized all 17 viruses, and sera from mice infected with any one virus variant cross-neutralized all of the other viruses. Thus, no antigenic differences that would potentiate vaccine failures were identified. These studies suggest that a single rabies virus strain or its G would protect globally against wild-type rabies viruses.

Animals↗

Cross protection of mice against different rabies virus isolates.

In an attempt to identify "atypical" strains which could account for vaccination failures, 10 street, one intermediate (DR19) and 4 fixed rabies virus isolates from men, cattle, dogs, cats, mongoose and vampire bats in five countries (Argentina, Brazil, Chile, Cuba, and France) were studied by cross-protection tests in mice. For the purpose of this study, any virus that killed more than 20% of the vaccinated mice challenged with that virus was considered "atypical". When the suckling mouse brain rabies vaccine was used, two "atypical" isolates were found: one, from a human case in Chile (91, 125 mouse passages) and the other, from a vampire bat in Brazil (DR19, 22 mouse passages). However, when mice immunized with a cell culture vaccine (PV-BHK) of a higher antigenic value than the brain vaccine, were challenged with those same isolates, mortality was below 20%. The fact that these two isolates killed enough vaccinated mice to be considered "atypical" could be related to antigenic differences between these viruses and those included in the vaccine. However, since this mortality was observed only in the mice immunized with the vaccine with a lower antigenic value, reasons are given why it could be attributed to other biological characteristics of those strains than antigenic differences. Causes for vaccines failures other than immunological differences of rabies virus strains are also analyzed and discussed.

Animals↗

T cells mediate cross-protective immunity between spotted fever group rickettsiae and typhus group rickettsiae.

Rickettsioses are severe infections caused by obligately intracellular bacteria that preferentially infect the endothelium lining the vasculature. The causative agents, rickettsiae, have been divided according to biological, genetic, and antigenic parameters into 2 main groups: spotted fever and typhus. They have not been thought to stimulate cross-reactive protective immune responses; however, in this study, we show that, in relevant animal models that mimic human rickettsial infections, there is reciprocal immunological cross-protection between spotted fever group and typhus group rickettsiae. Furthermore, we present evidence that T cells are responsible for this cross-immunity and that cross-stimulation of T cells also occurs in humans.

Adoptive Transfer↗