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PubMed2001

Protection of rainbow trout against infectious hematopoietic necrosis virus four days after specific or semi-specific DNA vaccination.

A DNA vaccine against a fish rhabdovirus, infectious hematopoietic necrosis virus (IHNV), was shown to provide significant protection as soon as 4 d after intramuscular vaccination in 2 g rainbow trout (Oncorhynchus mykiss) held at 15 degrees C. Nearly complete protection was also observed at later time points (7, 14, and 28 d) using a standardized waterborne challenge model. In a test of the specificity of this early protection, immunization of rainbow trout with a DNA vaccine against another fish rhabdovirus, viral hemorrhagic septicemia virus, provided a significant level of cross-protection against IHNV challenge for a transient period of time, whereas a rabies virus DNA vaccine was not protective. This indication of distinct early and late protective mechanisms was not dependent on DNA vaccine doses from 0.1 to 2.5 microg.

Animals↗

PubMed1995

Mechanisms for persistence of acute and chronic feline calicivirus infections in the face of vaccination.

The study was concerned with possible reasons for the persistence of both acute and chronic feline calicivirus (FCV)-induced disease and sustained oral carriage in the field in the face of routine FCV immunization. It was concluded from this study that: 1) the original FCV-F9 strain, which is the basis of most live vaccines, still generates cross-reactive antibodies against almost all field strains in California, 2) vaccine strains derived from FCV-F9 may not be as broadly cross-protective as the parent strain, 3) whole inactivated FCV-2280 vaccine evokes high virus neutralizing antibody titers with an equally broad spectrum of cross-reactivity as FCV-F9, 4) all vaccine strains of FCV cause acute disease signs and protracted oral shedding when administered orally, 5) strains isolated from the mouth five to ten weeks following oral inoculation can differ from parental virus, usually appearing more vaccine resistant, 6) cats previously infected with field or vaccine strains develop much less severe acute illness when subsequently infected with heterologous FCV strains but are not protected against the chronic carrier state. Therefore, the persistence of FCV in the field cannot be explained solely by the emergence of vaccine resistant strains and vaccine virus itself may contribute to both acute and chronic infection and disease.

Acute Disease↗

PubMed1991

Antigenic diversity of Cowdria ruminantium isolates determined by cross-immunity.

Antigenic diversity in five stocks of the tick-borne rickettsia Cowdria ruminantium, the causal agent of heartwater disease of ruminants, was studied by cross-immunity trials in goats and sheep. Complete absence of cross-protection was found only between the Kümm and Kwanyanga stocks, and in all other combinations there were various degrees of cross-immunity. Immunological strain differences were more pronounced in goats than in sheep.

Animals↗

PubMed1999

Inverse relationship between systemic resistance of plants to microorganisms and to insect herbivory.

Pre-inoculation of plants with a pathogen that induces necrosis leads to the development of systemic acquired resistance (SAR) to subsequent pathogen attack [1]. The phenylpropanoid-derived compound salicylic acid (SA) is necessary for the full expression of both local resistance and SAR [2] [3]. A separate signaling pathway involving jasmonic acid (JA) is involved in systemic responses to wounding and insect herbivory [4] [5]. There is evidence both supporting and opposing the idea of cross-protection against microbial pathogens and insect herbivores [6] [7]. This is a controversial area because pharmacological experiments point to negative cross-talk between responses to systemic pathogens and responses to wounding [8] [9] [10], although this has not been demonstrated functionally in vivo. Here, we report that reducing phenylpropanoid biosynthesis by silencing the expression of phenylalanine ammonialyase (PAL) reduces SAR to tobacco mosaic virus (TMV), whereas overexpression of PAL enhances SAR. Tobacco plants with reduced SAR exhibited more effective grazing-induced systemic resistance to larvae of Heliothis virescens, but larval resistance was reduced in plants with elevated phenylpropanoid levels. Furthermore, genetic modification of components involved in phenylpropanoid synthesis revealed an inverse relationship between SA and JA levels. These results demonstrate phenylpropanoid-mediated cross-talk in vivo between microbially induced and herbivore-induced pathways of systemic resistance.

Adaptation, Physiological↗

PubMedDate not supplied

Differentiation of celosia mosaic virus and asparagus virus 1 based on biological properties.

An attempt was made to distinguish between celosia mosaic virus (CIMV) and asparagus virus 1 (AV-1) based on biological properties, which hitherto was obscured from serological data from previous work. The host range of AV-1 was found to be a subset of that of CIMV and AV-1 was transmitted by the aphid Myzus persicae which, on the other hand, did not transmit CIMV. No evidence of cross-protection was obtained between these two viruses.

Animals↗

PubMed1987

Antibody immunotherapy of gram-negative bacterial sepsis.

Gram-negative bacterial sepsis continues to represent a significant cause of morbidity and mortality in hospitalized patients. Currently available medical therapy (antimicrobial agents, hemodynamic monitoring, aggressive fluid resuscitation, and nutritional support) for this disease process has reduced but not eliminated the severe consequences that may ensue. Recent investigations have demonstrated the ability of antibody directed against gram-negative bacterial lipopolysaccharide (LPS or endotoxin) to afford protection during experimental gram-negative bacillary sepsis. The core LPS-lipid A portion of endotoxin represents a determinant shared by many common gram-negative microorganisms that is luxuriantly expressed on the cell surface of rough mutants of Escherichia coli and Salmonella minnesota. These organisms or the outer membrane LPS isolated from them thus represent suitable immunogens for the development of cross-protective antibody preparations. Large quantities of highly cross-reactive antibody may potentially be obtained from several sources: murine or human monoclonal antibodies, immunization of large animals or humans with subsequent plasmapharesis and antibody isolation, affinity purification of large amounts of normal antibody, and pooling of prescreened lots of normal animal or human antibody that react to a particular bacterial antigen.

Antibodies, Bacterial↗

PubMed2000

Homologous and heterologous glycoproteins induce protection against Junin virus challenge in guinea pigs.

Tacaribe virus (TACV) is an arenavirus that is genetically and antigenically closely related to Junin virus (JUNV), the aetiological agent of Argentine haemorrhagic fever (AHF). It is well established that TACV protects experimental animals fully against an otherwise lethal challenge with JUNV. To gain information on the nature of the antigens involved in cross-protection, recombinant vaccinia viruses were constructed that express the glycoprotein precursor (VV-GTac) or the nucleocapsid protein (VV-N) of TACV. TACV proteins expressed by vaccinia virus were indistinguishable from authentic virus proteins by gel electrophoresis. Guinea pigs inoculated with VV-GTac or VV-N elicited antibodies that immunoprecipitated authentic TACV proteins. Antibodies generated by VV-GTac neutralized TACV infectivity. Levels of antibodies after priming and boosting with recombinant vaccinia virus were comparable to those elicited in TACV infection. To evaluate the ability of recombinant vaccinia virus to protect against experimental AHF, guinea pigs were challenged with lethal doses of JUNV. Fifty per cent of the animals immunized with VV-GTac survived, whereas all animals inoculated with VV-N or vaccinia virus died. Having established that the heterologous glycoprotein protects against JUNV challenge, a recombinant vaccinia virus was constructed that expresses JUNV glycoprotein precursor (VV-GJun). The size and reactivity to monoclonal antibodies of the vaccinia virus-expressed and authentic JUNV glycoproteins were indistinguishable. Seventy-two per cent of the animals inoculated with two doses of VV-GJun survived lethal JUNV challenge. Protection with either VV-GJun or VV-GTac occurred in the presence of low or undetectable levels of neutralizing antibodies to JUNV.

Animals↗

PubMed2004

Marburg virus-like particles protect guinea pigs from lethal Marburg virus infection.

Ongoing outbreaks of filoviruses in Africa and concerns about their use in bioterrorism attacks have led to intense efforts to find safe and effective vaccines to prevent the high mortality associated with these viruses. We previously reported the generation of virus-like particles (VLPs) for the filoviruses, Marburg (MARV) and Ebola (EBOV) virus, and that vaccinating mice with Ebola VLPs (eVLPs) results in complete survival from a lethal EBOV challenge. The objective of this study was to determine the efficacy of Marburg VLPs (mVLPs) as a potential vaccine against lethal MARV infection in a guinea pig model. Guinea pigs vaccinated with mVLPs or inactivated MARV developed MARV-specific antibody titers, as tested by ELISA or plaque-reduction and neutralization assays and were completely protected from a MARV challenge over 2000 LD50. While eVLP vaccination induced high EBOV-specific antibody responses, it did not cross-protect against MARV challenge in guinea pigs. Vaccination with mVLP or eVLP induced proliferative responses in vitro only upon re-exposure to the homologous antigen and this recall proliferative response was dependent on the presence of CD4+ T cells. Taken together with our previous work, these findings suggest that VLPs are a promising vaccine candidate for the deadly filovirus infections.

Animals↗

PubMed1975

Characterization by cyproheptadine of the dopamine-induced contraction in canine isolated arteries.

Spirally cut strips of isolated canine femoral and carotid arteries were used to characterize the vasoconstrictor effect of dopamine. A serotonin antagonist, cyproheptadine, 10- minus 7, 3 X 10- minus 7 and 10-minus 6 M, inhibited dopamine (pA2 = 7.46 plus or minus 0.11), tryptamine (pA2 = 7.38 plus or minus 0.09) and serotonin-induced contractions (pA2 = 7.59 plus or minus 0.09). Cyproheptadine shifted the threshold concentration of dopamine 2 log units to the right without altering norepinephrine response. In protection experiments, preincubation with serotonin (10-minus 5 M) for 10 minutes protected serotonin and tryptamine receptors from cyproheptadine (3 X 10-minus 7 M) and phenoxybenzamine (10-minus 6 M) blockade. Serotonin cross-protected dopamine receptors also. Reciprocally dopamine (10-minus 4 M) protected its own receptors as well as those for serotonin and tryptamine. Norepinephrine did not afford any protection of dopamine, serotonin or tryptamine receptors but did protect its own receptors from phenoxybenzamine blockade. The attempt to characterize the receptor subserving dopamine-induced contraction failed to confirm a relationship between dopamine and alpha adrenoceptors. Since dopamine, tryptamine and serotonin, unlike norepinephrine, were sensitive to cyproheptadine blockade, dopamine-induced contraction appeared to be mediated by a receptor closely related to serotonin receptors. Therefore, alpha adrenoceptors may not be exclusively involved in the vasoconstriction evoked by dopamine on canine vasculature.

Animals↗

PubMed1981

Potential use of attenuated langat E5 virus as a live vaccine -- long term protection against Russian spring-summer encephalitis virus in mice.

A single inoculation of Langat E5 virus provides 90-100% protection in mice against 3200-16000 lethal doses of Russian Spring-Summer Encephalitis (RSSE) virus when challenged 18 or 24 months later. The observed protection is found in the absence of neutralizing antibody (NA) against RSSE virus at the time of challenge but is associated with anamnestic NA response. Immunized mice have low titer short duration viremia. Immunized mice have late first detection and much lower multiplication in the brains, even though traces of virus could be detected in the brain up to 3 weeks following challenge. The observed protection results from sensitization due to immunization and quick host response following RSSE challenge resulting in significantly altered viral pathogenesis. Long term cross protection studies reported in this study and before coupled with the experience of the use of attenuated Langat E5 virus in humans volunteers suggests to its further testing as a live vaccine for prophylaxis against various members of Russian Spring-Summer virus complex throughout the world.

Animals↗

PubMed1981

Lysates of turkey-grown Pasteurella multocida: protection against homologous and heterologous serotype challenge exposures.

Pastereulla multocida organisms were separated from the blood of experimentally infected turkeys by differential centrifugation. An average of 92% of the residual host-cell contamination was removed from the pasteurellas by density gradient centrifugation in sucrose. Sucrose suspensions of the turkey-grown pasteurellas partially lysed after freezing and thawing. Treatment of freeze-thawed suspensions with DNAse, hyaluronidase, lysozyme, EDTA, and Triton X-100 did not influence their ability to induce protection against homologous and heterologous serotype challenge exposures. Lysozyme, EDTA, and Triton X-100 completely lysed the pasteurellas and rendered the cross-protection factor(s) filterable. Addition of adjuvant to completely lysed P multocida did not appear to enhance protection in turkeys against heterologous serotype challenge exposure. Adjuvant added to the pellet or supernatant fraction of centrifuged complete lysate enhanced protection in turkeys. Vaccines prepared from different serotypes of turkey-grown P multocida protected chickens and mice against homologous and heterologous serotype challenge exposures.

Animals↗

PubMed2003

Staphylococcus aureus strains isolated from bovine mastitis: virulence, antibody production and protection from challenge in a mouse model.

Septic arthritis in mice was used as a model to evaluate the virulence of Staphylococcus aureus and coagulase-negative staphylococci (CNS) isolated from cases of bovine mastitis. In addition, the model was used to evaluate the cross protection elicited by heterologous antibodies. Mice were intramuscularly inoculated with serial bacterial doses of different strains of S. aureus or CNS, for virulence determination; they were monitored for arthritis, gangrene or death up to 20 days. Antibody response, cross reactivity and resistance to challenge were tested by subcutaneous inoculation with a low dose of one of the S. aureus or CNS strains followed by challenge with two S. aureus strains. S. aureus alpha-hemolysin isolate was the most virulent, followed by alpha+beta-hemolysin and beta-hemolysin isolates. The least virulent isolates were the non-hemolytic S. aureus strains but even they were more virulent than the CNS strains tested. Antibodies against three different S. aureus antigens were detected by the ELISA in all mice that were inoculated with the S. aureus strains but not in any of those with the CNS strains. Immunoblot test against various S. aureus strains as antigens showed high cross-reactivity among the S. aureus strains but only a slight similarity, restricted to the bands above 36 kDa, with the CNS sera. Low-dose inoculation of alpha or alpha+beta strains before challenge with homologous and heterologous strains protected the mice, whereas the two beta strains provided only partial protection. The inoculations of non-hemolytic S. aureus or the CNS strains did not elicit any protection. Our findings demonstrate that pre-exposure of mice to a low dose of certain S. aureus strains could provide protection and that the antibodies produced could have an important protective role.

Animals↗

PubMed1992

Fasciola hepatica: molecular cloning, nucleotide sequence, and expression of a gene encoding a polypeptide homologous to a Schistosoma mansoni fatty acid-binding protein.

Immunization of mice with an antigenic polypeptide from Fasciola hepatica adult worms and having an apparent molecular mass of 12,000 Da (Fh12) has been shown to reduce the worm burden from challenge infection with Schistosoma mansoni by more than 50%. Moreover, mice infected with S. mansoni develop antibodies to Fh12 after 5-6 weeks of infection, indicating that this Fasciola-derived antigen is a cross-reactive, cross-protective protein. A lambda gt11 F. hepatica cDNA library was constructed from poly(A)+ RNA extracted from adult worms. A cDNA encoding a cross-reactive polypeptide (Fh15) was cloned by screening the F. hepatica lambda gt11 library with a monospecific, polyclonal rabbit antiserum against pure, native Fh12. The cDNA was sequenced and the predicted amino acid sequence revealed an open reading frame encoding a 132-amino-acid protein with a predicted molecular weight of 14,700 Da. This protein has significant homology to a 14-kDa S. mansoni fatty acid-binding protein. Comparison of the protective-inducing activity of recombinant Fh15 with that of purified Fh12 against schistosomes and Fasciola is warranted.

Amino Acid Sequence↗

PubMed1993

Protective effect of Salmonella typhimurium Re-LPS antiserum.

There is increasing evidence that antiserum to LPS can reduce the morbidity and mortality of Gram-negative bacterial infections. We report that antiserum to S. typhimurium SL 1102 (Re mutant strain) has excellent cross-protective activity. Antisera to these bacteria and to their Re-LPS were prepared in rabbits immunized with heat-killed bacterial cells and with Re-LPS preparations. Re-LPS antibody titers were tested by immune hemagglutination (IHA) and by ELISA. These antisera were found to be capable of protecting ICR mice against lethal challenge with S-type S. typhimurium 50014 (100 LD50), E. coli 0111:B4 (32 LD50), Pseudomonas aeruginosa (8 LD50) and Klebsiella pneumonia (16 LD50). We used gastric mucin (5%) as a virulence enhancing agent for the bacterial challenges. The IHA titer of antibody to the homologous strain proved to be much higher than that of other strains. Protection by the sera was 75-100%, 25% and 0% when injected 24, 48 or 72 h before the challenge, respectively. The survival rate was more than 50% when the antiserum was injected 5-7 h after challenge with a ten-fold or higher lethal dose. No protection was observed against such high challenge when the serum was injected later. According to these results, Re-LPS antiserum provides better protection than S-type specific antisera.

Animals↗

PubMed1991

Simian and feline immunodeficiency viruses: animal lentivirus models for evaluation of AIDS vaccines and antiviral agents.

Infection of captive macaques with simian immunodeficiency virus (SIV) and domestic cats with feline immunodeficiency virus (FIV), both discovered in the last five years, represent excellent animal models for infection of humans with the human immunodeficiency virus (HIV). Protection against challenge infection and protection against development of simian and feline acquired immunodeficiency syndrome has been achieved in each model by use of inactivated whole virus or virus-cell vaccines. A recombinant SIV envelope peptide vaccine has also proved efficacious. These vaccines have protected against 10-100 animal infectious doses of the homologous cell-free virus given systemically, and, in the simian model, apparently show cross protection against a heterologous strain of SIV. Protected animals appear free of any latent infection although late breakthroughs of infection in a few animals imply that not all vaccinated animals are completely protected. The mechanism of protection in the simian model apparently involves envelope antibody but the role of neutralizing antibody remains unclear. Questions remaining to be answered in both SIV and FIV models are: (1) the duration of immunity, (2) the extent of protection against heterologous strains and mucosal infection, (3) protection against infection with cell-associated virus and (4) the role, if any, of cellular immunity in vaccine protection. Initial attempts at post-infection immunotherapy with SIV vaccines have not yet been successful. The inactivated whole SIV and FIV vaccines offer a promising start and provide hope that a prophylactic AIDS vaccine will be developed. Use of these animal models for antiviral therapy is just now getting underway. Both models should prove especially useful for studies of prophylaxis and therapy, especially during the early stages of infection and for investigations on drug pharmacokinetics or toxicity that can not be done as well in HIV-infected humans. The animals will also be ideal for testing the pathogenicity of drug-induced mutant forms of SIV and FIV. For these purposes it will be necessary to create self-sustaining specific pathogen-free macaque and cat breeding colonies and provide increased housing facilities for infected animals. The future of AIDS research is crucially dependent on the long term availability of these animal models.

Animals↗

PubMed1996

Multiple immunizations with attenuated poxvirus HIV type 2 recombinants and subunit boosts required for protection of rhesus macaques.

Vaccine protocols involving multiple immunizations with molecularly attenuated vaccinia virus (NYVAC) or naturally attenuated canarypox virus (ALVAC) HIV-2 recombinants and subunit boosts have conferred longlasting protection against HIV-2 infection of macaques. Similar complex protocols using HIV-1 NYVAC and ALVAC recombinants and subunit boosts have provided cross-protection against HIV-2 challenge. Here a simplified three-immunization regimen over 24 weeks was tested in 18 juvenile rhesus macaques. Twelve macaques were immunized twice with NYVAC or ALVAC recombinants carrying HIV-2 env, gag, and pol genes. Subsequently, macaques in groups of three received either an additional recombinant immunization or an HIV-2 gp160 boost. Six control macaques received three immunizations of NYVAC or ALVAC vector alone and additionally alum at the third immunization. Macaques primed with ALVAC recombinant exhibited sporadic T cell proliferative activity, and all but one failed to develop neutralizing antibodies. In contrast, macaques primed with NYVAC recombinants had no T cell proliferative activity but exhibited neutralizing antibody titers (highest in the three recombinant group) that declined by the time of challenge. None of the macaques exhibited significant cytotoxic T lymphocyte activity. Following challenge at 32 weeks with HIV-2SBL6669 all macaques became infected. Thus, the three-immunization regimen is not sufficient to confer protective immunity in the HIV-2 rhesus macaque model. However, delayed infection in macaques immunized with the NYVAC-HIV-2 recombinant may have been associated with the development of memory B cells capable of providing a neutralizing antibody response on challenge.

AIDS Vaccines↗

PubMed1983

Preparation of a semisynthetic vaccine to Streptococcus pneumoniae type 3.

A semisynthetic vaccine to Streptococcus pneumoniae type 3 has been developed. The hexasaccharide [leads to 3)GlcpA beta(1 leads to 4)Glcp beta(1 leads to]3 was isolated from a partial acid hydrolysate of the capsular polysaccharide S3. It was coupled to stearylamine by reductamination with NaCNBH3 and then incorporated into liposomes. These haptenated liposomes were tested for immunogenicity in mice. They induced protection to a lethal dose (25 50% lethal doses) of S. pneumoniae type 3 and gave rise to immunoglobulin M antibodies. No cross-protection was observed against S. pneumoniae type 11.

Animals↗

PubMed1989

Monoclonal antibodies for dengue virus prM glycoprotein protect mice against lethal dengue infection.

Five murine monoclonal antibodies (Mabs) reactive against the prM glycoproteins of DEN-3 and -4 were used to passively protect mice in vivo against lethal challenge with homologous and heterologous dengue virus serotypes. Four of the 5 prM-reactive monoclonals cross-protected mice against heterologous challenge, whereas 1 protected against challenge with only the homologous serotype. Although in vitro binding to virions was readily demonstrated, only 2 of the prM Mabs had detectable neutralizing activity. The neutralizing activity could not be enhanced by anti-mouse immunoglobulin or complement. However, 4 of the 5 prM Mabs fixed complement. This is the first report of prM-specific Mabs that are protective in mice.

Antibodies, Monoclonal↗