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Results for “Cross Protection”

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PubMed1987

Protection of mice against dengue 2 virus encephalitis by immunization with the dengue 2 virus non-structural glycoprotein NS1.

Immunization of mice with the dengue 2 virus (DEN 2)-specified non-structural protein NS1 provided significant protection against intracerebral challenge with the virus in the absence of detectable neutralizing or other anti-virion antibody. NS1, purified from lysates of infected Vero cells by immunoaffinity chromatography, expressed an antigenic site(s) common to each of the four DEN serotypes, and hyperimmunization of rabbits with NS1 stimulated production of complement-fixing (CF) antibody with broad DEN serotype specificity. However, cross-protection was not observed: mice immunized with DEN 2 NS1 developed little or no heterologous CF antibody and were not protected against challenge with neurovirulent DEN 1. Induction of a protective immune response by NS1 suggests that it be considered for incorporation into possible synthetic or recombinant DNA DEN vaccines.

Animals↗

PubMed2003

A recombinant vaccine expressing a mammalian Mycobacterium sp. antigen is immunostimulatory but not protective in striped bass.

A recombinant vaccine was constructed for piscine mycobacteriosis utilizing a Brucella abortus strain RB51 vector expressing a mammalian Mycobacterium sp. 85A antigen. Juvenile striped bass were inoculated with the resulting construct at doses equivalent to 10(6), 10(7), 10(8), 10(9), and 10(10) colony-forming units/fish. Blood and tissue samples from these fish demonstrated significant specific humoral and cell-mediated immune responses towards the 85A antigen in a dose-dependent manner. However, survival studies determined that inoculated fish failed to demonstrate cross-protective responses after live Mycobacterium marinum challenge 70 days post-inoculation.

Amino Acid Sequence↗

PubMed1991

Homotypic and heterotypic protection against influenza virus infection in mice by recombinant vaccinia virus expressing the haemagglutinin or nucleoprotein of influenza virus.

Recombinant vaccinia virus expressing the influenza virus haemagglutinin (HA) or nucleoprotein (NP) genes from A/SW/Hong Kong/1/74 (H1N1) under the control of a hybrid promoter containing the P7.5 early promoter element and promoter of the gene encoding the major protein of cowpox virus A type inclusion body was constructed to investigate protective immunity against homologous and heterologous viruses in mice. These recombinant vaccinia viruses produced authentic influenza virus HA and NP in infected cells. The recombinant vaccinia virus-influenza virus HA conferred efficient subtype-specific protection although mice challenged with heterologous influenza viruses underwent initial infection. By contrast, immunization with the recombinant vaccinia-influenza virus NP limited virus multiplication in the lungs against challenge infection with all H1N1 and H3N2 influenza viruses examined, although less efficiently. These results will prompt the re-examination of the possibility of using the recombinant vaccinia virus-influenza virus NP as a cross-protective vaccine.

Animals↗

PubMed1988

Interaction of bass tapeworm, Proteocephalus ambloplitis, and Neoechinorhynchus sp. (Acanthocephala) in largemouth bass, Micropterus salmoides.

The number of plerocercoids of the bass tapeworm, Proteocephalus ambloplitis, in wild largemouth bass was negatively correlated (r = -0.94) with the number of Neoechinorhynchus sp. Competitive inhibition between the 2 parasites appeared to exist. Similarly, the numbers of Neoechinorhynchus sp. in wild bass decreased when adult bass tapeworms were present in the intestine. Proteocephalus ambloplitis plerocercoids used to challenge bass vaccinated with either P. ambloplitis adult or Neoechinorhynchus sp. antigens were smaller (P less than 0.05) when recovered than those used to challenge control bass. Based on preliminary results, both antigens might have enabled the bass to limit growth and/or development of the invading bass tapeworm, plerocercoids. Cross-protective immunity may be the reason for this occurrence, in which case, it could offer an explanation for competitive inhibition existing between P. ambloplitis and Neoechinorhynchus sp.

Acanthocephala↗

PubMed2004

Live attenuated HIV vaccines: pitfalls and prospects.

PURPOSE OF REVIEW: When simian immunodeficiency virus (SIV) deleted in the nef gene caused no disease in macaques and provided protection against wild-type SIV challenge, hopes were high that the removal of nef would convert a pathogenic immunodeficiency virus into a live attenuated vaccine. We seek to highlight recent studies focused on several major issues regarding live attenuated AIDS viruses as vaccine candidates: (1). safety, (2). efficacy, (3). the correlates of immune protection, and (4) the molecular determinants for lentiviral virulence or attenuation. RECENT FINDINGS: Nef-deletion mutants have retained virulence; compared with wild-type SIV, disease progression was slowed but not abrogated. After long-term observation, all adult macaques given SIVmac239delta3 exhibited immune dysfunction; over 50% had T-cell depletion, and 18% developed AIDS. Vaccine efficacy has been disappointing, with limited or no cross-protection and no protection against homologous virus challenge years after initial vaccination. To date, the correlates of protective immunity have defied precise definition; no dominant mechanism has yet emerged. Data from passive serum transfer and CD8+ T-cell depletion studies have raised the possibility that alternate mechanism of protection may be operative. Due to relentless viral replication and continuous selective pressure, initially benign viruses can generate virulent progeny with unpredictable genotypes. SUMMARY: Neither safety nor efficacy of the current live attenuated primate immunodeficiency virus vaccines has withstood the test of time. However, such viruses are invaluable tools to address two key questions: (1). what are the correlates of protection, and (2). what are the molecular determinants of viral immunopathogenesis?

AIDS Vaccines↗

PubMed2002

Characterization of protective immune responses induced by nasal influenza vaccine containing mutant cholera toxin as a safe adjuvant (CT112K).

Immune responses induced by a nasal influenza vaccine with a mutant cholera toxin (CT112K), known to be a safe adjuvant, were characterized in BALB/c mice to confirm the most suitable regimen of this vaccine for humans. Mice received a primary intranasal administration of the adjuvant (0.1 micro g)-combined PR8 vaccine (0.1 micro g) and a secondary administration of the PR8 vaccine alone (0.1 micro g) 4 weeks later. Two weeks after the secondary immunization, the mice were infected with a nonlethal or a lethal dose of PR8 viruses. Nasal and lung wash virus titers 1 or 3 days after infection indicated that complete protection could be provided by secondary immune responses, which had an immediate effect of preventing infection 2 weeks after the secondary immunization. In this two-dose regimen, high levels of secondary IgA, IgG and IgM antibody-forming cell (AFC) responses were induced in the nasal-associated lymphoid tissue and the spleen. In parallel with the AFC responses, high levels of nasal wash anti-PR8 HA IgA, and lung and serum IgG antibody (Ab) responses were induced 2 weeks after the secondary immunization. The two-dose regimen also induced accelerated delayed-type hypersensitivity responses, which exhibited almost the same peak height as that in the case of the primary response. In addition, the two-dose regimen induced a low memory cell activity of cytotoxic T lymphocytes, detected by in vitro culture of spleen cells. Thus, the immediate effect of preventing infection was mainly provided by the secondary Ab responses. Moreover, the levels of nasal wash IgA Abs correlated well with cross-protection against infection with variant viruses in the upper respiratory tract (RT). These results suggest that the major protective factors among Ab and T cell-mediated immune responses, which are induced by the two-dose regimen using CT112K-combined vaccines, are the cross-reactive IgA Abs in the upper RT and the less cross-reactive IgG Abs in the lower RT, and that the two-dose regimen is a suitable vaccination condition for humans.

Adjuvants, Immunologic↗

PubMed1998

Antigenic variation and cross-reactivity in Bacteroides forsythus clinical isolates detected by western blot.

Bacteroides forsythus is one of the etiologic agents of destructive periodontal diseases. Determining which antigenic components of the bacterium are recognized in the immune response of periodontitis patients is an important step in assessing strategies for vaccine development. The aim of this study was to identify the major strain-variable and cross-reactive antigens of B. forsythus clinical isolates recognized by serum IgG from patients with early-onset rapidly progressive periodontitis. Ten patient sera with measurable IgG against antigenic components of the species were identified by Western blot. Positive sera were tested by checkerboard ELISA to identify those most responsive to strain-variable antigens in nine clinical isolates and ATCC strain 43037. Correlation analysis of the ELISA data suggested that different subsets of isolates were preferentially recognized by different sera. Western blots revealed that certain sera also recognized major shared components across all the isolates, but preferential recognition of different isolate subsets by different patients was clearly confirmed. To determine if the variable antigens recognized were nonprotein, proteinase K-digested isolates were compared to undigested controls by Western blot. The main strain-variable antigens were proteinase resistant, while proteins at 200 and 210 kDa were identified as the major shared components. Two-dimensional SDS-PAGE revealed that these proteins are the quantitatively dominant heat-modifiable components of the cell envelope. Even though variable antigens are prominent in the immune response of patients, a cross-protective vaccine based on the shared envelope proteins of B. forsythus seems feasible in light of these observations.

Adult↗

PubMed1998

Different vaccine strategies used to protect against Theileria annulata.

SPAG-1, a sporozoite surface antigen of T. annulata, has previously been shown to elicit partial protection when used, as an hepatitis B core antigen fusion, to immunize cattle. The objective of this study was to try and improve the protective capacity of this antigen by enlisting different vaccine strategies. Cattle were immunized with SPAG-1, as a fusion protein with a His6 tag, either incorporated into ISCOMs, with or without the merozoite antigens TAMS 1-1 and 1-2, or with RWL as adjuvant three times at monthly intervals. Another group of cattle were immunized with p67, the T. parva sporozoite antigen, in RWL to assess whether any cross-protection could be induced. The animals were then challenged with an estimated LD50 of T. annulata sporozoites, and their ability to resist the infection was investigated. Serum responses and T-cell proliferative responses were analyzed throughout the trial. Post-challenge analyses included lymph node biopsies and blood smears to check for the presence of parasites, routine hematological parameters, and observation for clinical manifestations of the disease. The results of this trial will be discussed.

Animals↗

PubMed1999

Lassa fever: implications of T-cell immunity for vaccine development.

Lassa fever is a re-emerging viral hemorrhagic fever, which causes significant human morbidity in endemic regions of West Africa. Attempts to vaccinate against this virus in animal models including non-human primates have revealed that eliciting a strong cellular immune response protects from clinical disease, but not infection, in the absence of measurable neutralizing antibodies. As there is renewed interest in developing a vaccine against Lassa fever for use in humans, several questions should be addressed in view of the scarce knowledge of the mechanisms of natural immunity against this disease. MHC-dependency of a vaccine relying mainly on the induction of T-cell immunity and its ability to cross-protect against different Lassa virus strains will be important issues. Furthermore, the question whether the vaccine can prevent human-to-human transmission of the virus should be discussed and the possibility that vaccination could predispose to immunopathology should be excluded. We are addressing some of the above mentioned problems concerning natural immunity through field studies in the Republic of Guinea, West Africa, and are presently studying the CD4 cell responses of Lassa antibody positive subjects on the basis of T-cell proliferation assays using recombinant Lassa virus proteins.

Animals↗

PubMed1992

Multicellular oxidant defense in unicellular organisms.

Although catalase is thought to be a major defense against hydrogen peroxide (H2O2), the catalase activity within individual Escherichia coli fails to protect against exogenous H2O2. Contrary to earlier reports, we find that dilute suspensions of wild-type and catalase-deficient E. coli are identical in their sensitivity to H2O2, perhaps because even wild-type, catalase-positive E. coli cannot maintain an internal/external concentration gradient of this highly diffusible oxidant. However, concentrated suspensions or colonies of catalase-positive E. coli do preferentially survive H2O2 challenge and can even cross-protect adjacent catalase-deficient organisms. Furthermore, high-density catalase-positive--but not catalase-negative--E. coli can survive and multiply in the presence of competitive, peroxide-generating streptococci. These observations support the concept that bacterial catalase may defend colonial, but not individual, E. coli against environmental H2O2. Group protection by the activity of enzymes that mitigate oxidative stress may have been a driving force in the evolution of multicellular organisms.

Biological Evolution↗

PubMed2005

Multiple diagnostic techniques identify previously vaccinated individuals with protective immunity against monkeypox.

Approximately 50% of the US population received smallpox vaccinations before routine immunization ceased in 1972 for civilians and in 1990 for military personnel. Several studies have shown long-term immunity after smallpox vaccination, but skepticism remains as to whether this will translate into full protection against the onset of orthopoxvirus-induced disease. The US monkeypox outbreak of 2003 provided the opportunity to examine this issue. Using independent and internally validated diagnostic approaches with >or=95% sensitivity and >or=90% specificity for detecting clinical monkeypox infection, we identified three previously unreported cases of monkeypox in preimmune individuals at 13, 29 and 48 years after smallpox vaccination. These individuals were unaware that they had been infected because they were spared any recognizable disease symptoms. Together, this shows that the US monkeypox outbreak was larger than previously realized and, more importantly, shows that cross-protective antiviral immunity against West African monkeypox can potentially be maintained for decades after smallpox vaccination.

Animals↗

PubMed1998

Comparison of the PspA sequence from Streptococcus pneumoniae EF5668 to the previously identified PspA sequence from strain Rx1 and ability of PspA from EF5668 to elicit protection against pneumococci of different capsular types.

PspA (pneumococcal surface protein A) is a serologically varied virulence factor of Streptococcus pneumoniae. In mice, PspA has been shown to elicit an antibody response that protects against fatal challenge with encapsulated S. pneumoniae, and the protection-eliciting residues have been mapped to the alpha-helical N-terminal half of the protein. To date, a published DNA sequence for pspA is available only for S. pneumoniae Rx1, a laboratory strain. PspA/EF5668 (EF5668 indicates the strain of origin of the PspA) is serologically distinct from PspA/Rx1. Sequencing of the gene encoding PspA/EF5668 revealed 71% identity with that of PspA/Rx1. The greatest amount of divergence between the two proteins was seen in their alpha-helical portions, which are surface exposed and probably under selective pressure to diversify serologically. In spite of the diversity within the alpha-helical regions of PspAs, we have observed that recombinant PspA (rPspA)/EF5668, like rPspA/Rx1, can elicit cross-protection against pneumococci of different capsular and PspA serological types.

Amino Acid Sequence↗

PubMed1984

Virus specificity of cytotoxic T lymphocytes generated during acute lymphocytic choriomeningitis virus infection: role of the H-2 region in determining cross-reactivity for different lymphocytic choriomeningitis virus strains.

We have compared the relatedness of five different strains of lymphocytic choriomeningitis virus (LCMV) as assessed by LCMV-specific cytotoxic T lymphocytes (CTL). Several different mouse strains were injected with each of the five LCMV strains, and the cross-reactivity of virus-specific CTL generated during the acute infection was tested by killing on a panel of target cells infected with the various LCMV strains. We found that the cross-reactivity pattern of LCMV-specific CTL generated in mice of H-2d haplotype (BALB/c WEHI and DBA/2) was strikingly different from that in mice of H-2b haplotype (C57BL/6 and C3H.Sw/Sn), suggesting that the fine specificity of LCMV-specific CTL is a function of the H-2 region. The characteristic cross-reactivity patterns were also observed in (C57BL/6 X DBA/2)F1 mice, demonstrating that the repertoire of the H-2b- and H-2d-restricted LCMV-specific CTL is not changed as a result of complementation by gene products of the other major histocompatibility haplotype. Studies with congenic BALB.B10 and (BALB.B10 X BALB/c)F1 mice firmly established that the characteristic cross-reactivity patterns of LCMV-specific CTL map to the H-2 region and are not influenced by background genes outside the major histocompatibility locus. These results suggest that LCMV determinants seen in the context of H-2d-restricting elements are different from those seen in the context of H-2b-restricting elements. Moreover, our studies show that CTL can be used as probes for dissecting differences among various LCMV strains, but the degree of relatedness between the different LCMV strains is not absolute when measured by CTL recognition. Since the H-2 region regulates the fine specificity of CTL generated during LCMV infection in its natural host, the degree of cross-protective immunity developed during a viral infection apparently depends on the major histocompatibility haplotype. The importance of these findings lies in understanding susceptibility or resistance of various host populations to viral infections and in designing vaccination programs to provide immunity.

Animals↗

PubMed2001

Genetic immunization with the region encoding the alpha-helical domain of PspA elicits protective immunity against Streptococcus pneumoniae.

Pneumococcal surface protein A (PspA) is a pneumococcal virulence factor capable of eliciting protection against pneumococcal infection in mice. Previous studies have demonstrated that the protection is antibody mediated. Here we examined the ability of pspA to elicit a protective immune response following genetic immunization of mice. Mice were immunized by intramuscular injections with a eukaryotic expression vector encoding the alpha-helical domain of PspA/Rx1. Immunization induced a PspA-specific serum antibody response, and immunized mice survived pneumococcal challenge. Survival and antibody responses occurred in a dose-dependent manner, the highest survival rates being seen with doses of 10 microg or greater. The ability of genetic immunization to elicit cross-protection was demonstrated by the survival of immunized mice challenged with pneumococcal strains differing in capsule and PspA types. Also, immunized mice were protected from intravenous and intratracheal challenges with pneumococci. Similar to the results seen with immunization with PspA, the survival of mice genetically immunized with pspA was antibody mediated. There was no decline in the level of protection 7 months after immunization. These results support the use of genetic immunization to elicit protective immune responses against extracellular pathogens.

Animals↗

PubMed1986

Murine melanoma-specific tumor rejection activity elicited by a purified, melanoma-associated antigen.

B700 is a melanoma-specific glycoprotein antigen, with a m.w. of 65,000 and an isoelectric point of 4.5; this antigen has been shown to bear significant sequence homology to a normally occurring protein, serum albumin. The production of B700 is apparently restricted to all the murine melanomas tested, since a variety of other transformed and untransformed cell lines do not contain detectable levels of this antigen. The capacity of B700 to function as a tumor-specific transplantation antigen (TSTA) is demonstrated in this study. This activity has been titrated, and it is shown that mice immunized with B700 are able to significantly inhibit the growth of B16 F10 melanomas after subcutaneous challenge; immunized mice can also inhibit the establishment and growth of experimental metastases in the lungs after i.v. challenge with B16 melanoma cells. The TSTA was found to cross-protect also against challenge with two other murine melanoma lines, JB/RH and K1735, but was specific in that the growth of two nonmelanoma lines (RBL-5 leukemia and MCA-105 sarcoma) was not affected. B700 is also shown in this study to be unrelated to other known murine tumor antigens, or to murine leukemia virus antigens. It is further shown that mice immunized with B700 produced antibodies specific to B700 that were not cross-reactive with albumins from various mammalian sources.

Animals↗

PubMed1985

A common major surface antigen on amastigotes and promastigotes of Leishmania species.

Enzymatic surface iodination and biosynthetic labeling with [35S]methionine, combined with immunoprecipitation by sera from patients with different forms of Leishmaniasis revealed a 65,000 Mr glycoprotein as the immunodominant moiety in promastigotes and amastigotes of the nine Leishmania species and isolates examined. Sera from patients with one form of Leishmaniasis recognized this component strongly, not only in the homologous, but also in the heterologous species. In addition to the crossreactivity displayed by immune sera, the 65,000 Mr glycoprotein (gp) common to all Leishmania species presented a characteristic shift to Mr 50,000 when samples were run in sodium dodecyl sulfate-polyacrylamide gel electrophoresis under nonreducing conditions. These results are in agreement with our previous studies (7), where a simple and similar profile was obtained for several geographic isolates of L. donovani, with a major surface glycoprotein of 65,000 Mr displaying the same characteristics described here. The structural similarity of the major 65,000 Mr gp of the six Leishmania species was demonstrated by Cleveland mapping. It is suggested that immunological specificities may be contributed by minor differences in glycosylation of this molecule. In keeping with recent data (13-15), where strong cross protection among different Leishmania species has been obtained by prophylactic immunization with irradiated whole promastigotes, this glycoprotein may be a good candidate for an antigen to be used for immunoprophylaxis of all forms of Leishmaniasis.

Antigens, Protozoan↗

PubMed1996

[Immunization with potential Salmonella enteritidis mutants-- 2. Investigations on the attenuation and immunogenicity for mice and young hens].

Adenine-amino acid auxotrophic Salmonella Enteritidis double mutants were investigated for their in vivo stability, attenuation und immunogenicity using NMRI-mice and SPF-chicks. All mutants used were stable in vivo and attenuated. Two mutants were selected for immunization experiments in chickens according to their protective ability after a single intraperitoneal immunization in NMRI-mice using a homologous and heterologous challenge. After two oral immunizations and homologous oral challenge with the S. Enteritidis wild type strain 6403Nalr, a significant difference (p < 0.01) was demonstrated between the mean caecal bacterial counts of immunized and control chicks. Examination of liver samples revealed a significantly lower degree of colonization of internal organs (p < 0.01) in immunized birds. There was no evidence of cross protection against S. Typhimurium using S. Enteritidis mutants.

Animals↗

PubMed1995

Protection against non-typable Haemophilus influenzae following sensitization of gut associated lymphoid tissue: role of specific antibody and phagocytes.

Rats intestinally immunized with whole killed non-typable Haemophilus influenzae clear this organism from the lungs faster than non-immunized rats. This study investigated the role of antibody and phagocytes in the clearance mechanism. First, dose-response experiments demonstrated that while lowering the dose of non-typable H. influenzae reduced the level of detectable specific antibody in bronchial washings, the ability to accelerate bacterial clearance persisted to much lower doses. Second, specificity experiments showed that intestinal immunization with non-typable H. influenzae cross-protected against Pseudomonas aeruginosa, even though antibodies were not absorbed out of serum by incubation with P. aeruginosa. Third, serum antibody was shown to be bactericidal for non-typable H. influenzae in the presence of complement (P < 0.05), while bronchial washings antibody was not. The bactericidal effect of the serum was abrogated by the addition of bronchial washings. Fourth, an ELISA quenching assay demonstrated that neutrophils from intestinally immunized rats were able to phagocytose more bacteria in a given time period (P < 0.05) than unimmunized rats and rats immunized by other routes. In the fifth experiment, the chemotactic response of neutrophils to casein was shown to be significantly depressed by the addition of bronchial washings obtained from immunized rats (P < 0.01). It is proposed that specific antibody in bronchial washings does not have a direct role in opsonizing bacteria for killing or phagocytosis, but instead has an anti-inflammatory effect. Non-specific effectors such as neutrophils driven by specific immune cells are a likely means of clearance of bacteria following intestinal immunization and acute challenge.

Animals↗