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PubMed1998

The effect of conjugation on immunogenicity and potency of protein carriers of polyribosylribitol phosphate (PRP) conjugated vaccines in the mouse model.

Immunogenicity and vaccine potency of carrier proteins of two different PRP-tetanus toxoid (PRP-T) conjugated vaccines, produced using different size PRP (Act-Hib & Amvax Hib-T), and one PRP-CRM197 (Hib-TITER) were studied. The immunogenicity and the vaccine potency of the carrier component of the tested PRP-conjugated vaccines, and their influences on the potency of the tetanus toxoid (T) and of the diphtheria toxoid (D) component of diphtheria toxoid-tetanus toxoid-acellular pertussis-inactivated polio vaccine (DTaP-IPV) were variable. The T component of Act-Hib (large size PRP) was as immunogenic and potent as the T component of the DTaP-IPV vaccine, and a combination of Act-Hib and DTaP-IPV resulted in a more than five-fold increase in the potency of the T However, Amvax Hib-T (small size PRP) did not show any anti-T response on its own, and a combination of Amvax Hib-T and DTaP-IPV did not affect the T potency of the DTaP-IPV vaccine. In immunogenicity studies with multiple shots, Hib-TITER (small size PRP) produced significantly less anti-D antibodies than non-conjugated D. Hib-TITER did not show any D potency on its own, while a combination of a Hib-TITER and DTaP-IPV increased the potency of the D component of DTaP-IPV vaccine significantly. Thus, in the case of a combination of T-and D-containing vaccines with a PRP-conjugated vaccine in which either T or CRMI 97 has been used as the carrier, the influence of these carriers on basic immunogenicity and vaccine potency of T and D, respectively, should be considered carefully. We propose the techniques employed in this study for the quality control of combined vaccines consisting of diphtheria, tetanus, and PRP-conjugated vaccines.

Animals↗
PubMed1986

Influence of beta-lactam antibiotics and ciprofloxacin on composition and immunogenicity of Escherichia coli outer membrane.

The effects of subinhibitory concentrations of different beta-lactam antibiotics and one quinolone on the sedimentation of outer membranes (OMs) of Escherichia coli and on the qualitative properties and immunogenicity of OM components were studied. Membranes were prepared by osmotic lysis of plasmolyzed bacteria. OM and cytoplasmic membrane vesicles were separated by sucrose density ultracentrifugation. Two peaks of OM vesicles with different buoyant densities could be isolated; the quantitative contribution of these to the total OM varied, depending upon the growth phase. In early log phase, the OM consisted mainly of lighter material; in late log and stationary phases, the OM consisted mainly of heavier material. Moxalactam, imipenem, and ciprofloxacin inhibited the formation of heavier material in all growth phases. The immunogenicity of OM vesicles was tested in mice by the hemolytic plaque test. The lighter OM material was markedly less immunogenic than the heavier OM material. The vesicles from antibiotic-treated bacteria and those from early-log-phase cells were less immunogenic than vesicles from untreated late-log-phase and stationary-phase bacteria. These changes were found for the immune response against lipopolysaccharides, as well as against OM proteins. Thus, the immunogenicity of OM components seems to be dependent upon the quantitative composition of lighter and heavier compounds, which is strongly influenced by growth phase and treatment with certain antibiotics.

Animals↗
PubMed2000

A double-blind, adjuvant-controlled trial of human immunodeficiency virus type 1 (HIV-1) immunogen (Remune) monotherapy in asymptomatic, HIV-1-infected thai subjects with CD4-cell counts of >300.

We examined the effect of a human immunodeficiency virus (HIV)-specific immune-based therapy in Thailand, where access to antiviral drug therapy is limited. A 40-week trial was conducted with 297 asymptomatic, HIV-infected Thai subjects with CD4-cell counts greater than 300 microl/mm(3). Subjects were randomized to receive either HIV type 1 (HIV-1) immunogen (Remune; inactivated HIV-1 from which gp120 is depleted in incomplete Freund's adjuvant or adjuvant control at 0, 12, 24, and 36 weeks at five different clinical sites in Thailand. Neither group received antiviral drug therapy. The a priori primary endpoint for the trial was changes in CD4-cell counts with secondary parameters of percent changes in CD8-cell counts (percent CD4, CD8, and CD4/CD8) and body weight. Subsets of subjects were also examined for changes in plasma HIV-1 RNA levels, Western blot immunoreactivity, and HIV-1 delayed-type hypersensitivity (DTH) skin test reactivity. There was a significant difference in changes in CD4-cell counts that favored the HIV-1 immunogen-treated group compared to those for the adjuvant-treated control group (P<0.05). On average, for HIV-1 immunogen-treated subjects CD4-cell counts increased by 84 cells by week 40, whereas the increase for the control group was 38 cells by week 40. This increase in CD4-cell count was associated with increased HIV-specific immunogenicity, as shown by Western blotting and enhanced HIV-1 DTH skin reactivity. No significant differences in adverse events were observed between the groups. The results of this trial suggest that HIV-1 immunogen is safe and significantly increases CD4-cell counts and HIV-specific immunity compared to those achieved with the adjuvant control in asymptomatic HIV-1-infected subjects not taking antiviral drugs.

AIDS Vaccines↗
PubMed2006

Group B streptococcal type II and III conjugate vaccines: physicochemical properties that influence immunogenicity.

Recent efforts toward developing vaccines against group B streptococci (GBS) have focused on increasing the immunogenicity of GBS polysaccharides by conjugation to carrier proteins. However, partial depolymerization of GBS polysaccharides for the production of vaccines is a difficult task because of their acid-labile, antigenically critical sialic acids. Here we report a method for the partial depolymerization of type II and III polysaccharides by mild deaminative cleavage to antigenic fragments with reducing-terminal 2,5-anhydro-d-mannose residues. Through the free aldehydes of their newly formed end groups, the fragments were conjugated to tetanus toxoid by reductive amination. The resulting conjugates stimulated the production in animals of high-titer type II- and III-specific antibodies which induced opsonophagocytic killing of type II and III strains of group B streptococci. For the type II conjugates, immunogenicity increased as oligosaccharide size decreased, whereas for type III conjugates, the size of the oligosaccharides did not significantly influence immunogenicity. When oligosaccharides of defined size were conjugated through sialic acid residues, the resulting cross-linkages were shown to affect immunogenicity. When oligosaccharides were conjugated through terminal aldehyde groups generated by deamination, modification of the exocyclic chain of sialic acid did not influence immunogenicity.

Amination↗
PubMed1993

Immune response of rabbits to lipid A: influence of immunogen preparation and distribution of various lipid A specificities.

Sixty-two rabbit anti-lipid A serum samples were compared with respect to the immunogens used (synthetic lipid A and partial structures, natural lipid A, or acid-treated bacteria). Immunoglobulin (Ig) type-specific differences in rabbit response between liposomal membrane-embedded (LME) and other lipid A immunogens were found: LME lipid A elicited predominantly IgM antibodies. Previous findings of equally good immune responses to synthetic lipid A and acid-treated bacteria (L. Brade, E.T. Rietschel, S. Kusumoto, T. Shiba, and H. Brade, Infect. Immun. 51:110-114, 1986, and L. Brade, E.T. Rietschel, S. Kusumoto, T. Shiba, and H. Brade, Prog. Clin. Biol. Res. 231:75-97, 1987) turned out to be restricted to complement-fixing antibodies; IgG titers of sera against free lipid A (whether synthetic or natural) were significantly lower than those raised with bacteria. The results indicated an increase in IgG content of sera from LME lipid A over other free lipid A immunogens to acid-treated bacteria. These data underline the importance of the physicochemical environment for the immunogenicity of lipid A. As a second objective, the presence of various lipid A antibody specificities was tested with synthetic lipid A antigens. Antibodies to monophosphoryl lipid A were detected only in sera raised with monophosphoryl immunogens. Reactivity with monosaccharide partial structures of lipid A was found both in sera against monophosphoryl lipid A and in 60% of sera against bisphosphoryl lipid A. In the former, monosaccharide reactivity was of a magnitude similar to that of reactivity with lipid A; in sera against bisphosphoryl lipid A, it was lower. No reactivity or only marginal reactivity was found with phosphate-free lipid A, thus emphasizing the role of phosphate substitution for the lipid A epitopes recognized.

Animals↗
PubMed1997

Mucosal immunogenicity of a recombinant Salmonella typhimurium-cloned heterologous antigen in the absence or presence of coexpressed cholera toxin A2 and B subunits.

An avirulent Salmonella typhimurium vaccine strain expressing a streptococcal protein adhesin and a similar clone which produces the same streptococcal antigen linked to the cholera toxin (CT) A2 and B subunits (CTA2/B) were compared for the ability to induce antibody responses to the expressed heterologous antigen after oral or intranasal immunization of mice. Expression of cloned immunogens in these systems is temperature regulated, being optimal at 37 degrees C, and the two clones under comparison were shown to produce similar levels of the streptococcal antigen. Both clones were found to stimulate high levels of serum immunoglobulin G (IgG) and mucosal IgA antibodies to the cloned immunogen. A consistent trend was observed toward higher mucosal IgA but lower serum IgG responses in the case of the S. typhimurium vector that coexpressed CTA2/B, a potential mucosal adjuvant, regardless of the route of administration. Also noteworthy was the capacity of these antigen delivery systems to induce anamnestic systemic and secretory responses to the cloned immunogen 15 weeks after the primary immunization, despite preexisting immunity to the Salmonella vectors. These antibody responses were sustained for at least 7 months following the booster immunization, at which time the secretory IgA antibody levels were significantly higher in mice given the Salmonella clone that coexpressed CTA2/B. Although the serum IgG response against the Salmonella vector was characterized by a high IgG2a/IgG1 ratio (indicative of the T helper type 1 [Th1]/Th2 profile), a mixed IgG1 and IgG2a pattern was observed for the carried heterologous antigen, which displayed a dominant IgG1 response when administered as a purified immunogen. Our findings indicate that the recombinant streptococcal antigen and CTA2/B are strong immunogens when expressed by the antigen delivery system used in this study and suggest that CTA2/B may have an additional immunoenhancing activity in the mucosal compartment besides its ability to target antigen uptake into the mucosal inductive sites. CTA2/B may thus be useful as an S. typhimurium-cloned adjuvant for coexpressed protein antigens.

Animals↗
PubMed1999

B- and T-cell immune responses to pneumococcal conjugate vaccines: divergence between carrier- and polysaccharide-specific immunogenicity.

Conjugation of various serotypes of pneumococcal polysaccharide (PnPS) to carrier protein enhances the magnitude of the polysaccharide-specific antibody response, presumably by eliciting T-cell help. However, variability in PnPS serotype-specific immunogenicity has been observed. CBA/J mice immunized with either 6B or 19F PnPS conjugated to the protein carrier Cross Reactive Material(197) (CRM(197)) produce a strong anti-PnPS antibody response; however, when mice are immunized with 23F PnPS conjugated to CRM(197), they fail to produce a significant anti-PnPS response. In order to determine whether this difference was related to alterations in antigen processing of the carrier protein and the subsequent T-cell responses, we studied proliferation of lymphocytes from CBA/J mice immunized with CRM(197) alone or conjugated to 6B, 19F, or 23F PnPS. T-cell proliferative responses to synthetic peptides demonstrated that lymph node cells elicited by the poorly immunogenic conjugate 23F-CRM(197) recognized many, but not all, of the epitopes recognized by lymph node cells elicited by 6B- and 19F-CRM(197) as well as additional epitopes. Despite marked differences in PnPS-specific immunogenicity, all mice made high titers of CRM(197) antibodies of the immunoglobulin G(1) isotype. Cells from mice immunized with any of the conjugates yielded vigorous T-cell responses to whole antigen. We conclude that the serotype of PnPS can alter the peptide specificities of T-cell responses, but even a poorly immunogenic PnPS conjugate can elicit a significant T-cell response. Thus, conjugation of PnPS to a carrier protein that elicits carrier-specific T- and B-cell responses does not necessarily enhance PnPS immunogenicity.

Animals↗
PubMed2003

Efficacy of the 26-kilodalton outer membrane protein and two P5 fimbrin-derived immunogens to induce clearance of nontypeable Haemophilus influenzae from the rat middle ear and lungs as well as from the chinchilla middle ear and nasopharynx.

The rat middle ear and lung clearance model has been used to show that the nontypeable Haemophilus influenzae 26-kDa outer membrane protein OMP26 is highly efficacious as a mucosal immunogen, inducing significantly enhanced clearance in immunized rats upon direct challenge of these two anatomic sites. Similarly, the chinchilla model of middle ear and nasopharyngeal clearance has been used to show that two P5 fimbrin adhesin-derived immunogens, LB1 and lipoprotein D (LPD)-LB1(f)(2,1,3), are highly efficacious as parenteral immunogens. Both induced significantly augmented clearance of nontypeable H. influenzae upon challenge of these sites. Here, these three nontypeable H. influenzae immunogens in addition to six bovine serum albumin and keyhole limpet hemocyanin conjugates of the synthetic peptide LB1(f) were assayed for relative efficacy in the reciprocal rodent model system. OMP26 was assayed in the chinchilla host by a parenteral immunization route, with clearance of the middle ear and nasopharynx used as outcome measures. Both LB1 and LPD-LB1(f)(2,1,3) were assayed in the rat host with a mucosal immunization route and clearance of nontypeable H. influenzae from the lungs and middle ears as outcome measures. Both of the immunogens were found to induce a high-titered and specific immune responses in the heterologous host system. Moreover, each was found to be highly efficacious in the reciprocal host system, providing strong support for the continued development and inclusion of both OMP26 and P5 fimbrin-derived peptides as candidate vaccine antigens directed at otitis media caused by nontypeable H. influenzae.

Amino Acid Sequence↗
PubMed1969

Cholera toxins: immunogenicity of the rabbit ileal loop toxin and related antigens.

A method of assay of immunogenic potency of the cholera gut toxin is described; it is based on the relation of dose of antigen to neutralizing antibody titer produced in the rabbit under defined conditions and allows quantification of immunogenicity as immunogenic units per milligram of protein. Evidence, based on immunogenicity and rabbit ileal loop toxicity, is presented which indicates that the positively charged fraction of liquid-culture supernatant fluid eluted in deionized water from diethylaminoethyl Sephadex, or in electrolyte from carboxymethyl Sephadex, is a complex made up of a nonantigenic toxic moiety, a nontoxic protein component which elicits the formation of toxin-neutralizing antibody, and an inactive fraction. The complex may also be dissociated in high-salt concentrations with apparent recombination of the toxic moiety with a nondialyzable constituent of peptone to give a negatively charged complex. The immunogenic component is found in nontoxic supernatant fluids of cultures grown at pH 6.5 or in media deficient in peptone. It is also present in the nontoxic fraction eluted from diethylaminoethyl Sephadex in electrolyte or in deionized water from carboxymethyl Sephadex. When separated from the positively charged toxic moiety, the net charge of the antigen is reduced as shown by immunoelectrophoresis. On primary fractionation, the antigen may be associated with a minor antigenic component of the negatively charged complex containing a major antigen eliciting vibriocidal antibody formation, but antisera to the toxin antigen preparations, either in this form or freed of antigenic contamination by recycling, do not contain vibriocidal antibody. It is suggested that this antigen be designated the T (toxin) antigen, and the antigen producing vibriocidal antibody the V antigen. These two antigens would appear to represent the major antigenic specificities associated with the antitoxic and antibacterial elements of the immune response to infection.

Animals↗
PubMed1984

Immunogenicity of herpes simplex virus glycoproteins gC and gB and their role in protective immunity.

The relative antigenicity of the individual herpes simplex virus type 1 (KOS) glycoproteins gC and gB was analyzed in BALB/c mice by using KOS mutants altered in their ability to present these antigens on cell surface membranes during infection. The mutants employed were as follows: syn LD70 , a non-temperature-sensitive mutant defective in the synthesis of cell surface membrane gC; tsF13 , a temperature-sensitive mutant defective in the processing of the precursor form of gB to the mature cell surface form at 39 degrees C; and ts606 , an immediate early temperature-sensitive mutant defective in the production of all early and late proteins including the glycoproteins. By comparing the relative susceptibility to immunolysis of mouse 3T3 cells infected at 39 degrees C with wild-type virus, presenting the full complement of the glycoprotein antigens, gC, gB, and gD, with target cells infected with mutants presenting only subsets of these antigens, we determined that a major portion of cytolytic antibody contained in hyperimmune anti-herpes simplex virus type 1 (KOS) mouse antiserum was directed against glycoproteins gC and gB. The relative immunogenicity of wild-type and mutant virus-infected cells also was compared in BALB/c mice. Immunogen lacking the mature form of gB induced a cytolytic antibody titer comparable to that of the wild-type virus, whereas that lacking the mature form of gC showed a 70% reduction in titer. The absence of the mature cell surface forms of gB and gC in immunogen preparations resulted in a 4- to 15-fold reduction in in virus neutralizing titer. Animals immunized with ts606 -infected cells (39 degrees C) induced relatively little virus-specific cytolytic and neutralizing antibody. Analysis of the glycoprotein specificities of these antisera by radioimmunoprecipitation showed that the antigens immunoprecipitated reflected the viral plasma membrane glycoprotein profiles of the immunogens. The absence of the mature forms of gC or gB in the immunizing preparation did not appreciably affect the immunoprecipitating antibody response to other antigens. Mice immunized with wild-type and mutant virus-infected cells were tested for their resistance to intracranial and intraperitoneal challenge with the highly virulent WAL strain of herpes simplex virus type 1. Despite the observed alterations in serum virus-specific antibody induced with the individual immunogens, all animals survived an intraperitoneal challenge of 10 50% lethal doses. However, differences in the survival of animals were obtained upon intracranial challenge.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2004

Fusion to C3d enhances the immunogenicity of the E2 glycoprotein of type 2 bovine viral diarrhea virus.

The use of DNA and protein subunit vaccines in animals provides an opportunity to introduce vaccines that are arguably the safest that can be developed. For that reason, considerable effort is under way to devise methods of enhancing the immunogenicity of such vaccines. Seven years ago it was shown that fusing complement fragment C3d to hen egg lysozyme (HEL) enhanced the immunogenicity of HEL 10,000-fold. Based on this observation, we decided to evaluate the effect of C3d on the immunogenicity of the E2 protein of bovine viral diarrhea virus (BVDV). E2 is the major target of neutralizing antibody during BVDV infection. To test the effect of C3d on E2 immunogenicity, expression cassettes encoding a secreted form of E2 alone (E2s) or E2 fused to three copies of murine C3d (E2s-C3d) were constructed. The proteins were purified from the supernatants of transfected cells and used to immunize mice. The immune response was monitored by an enzyme-linked immunosorbent assay (ELISA) for E2s-specific antibody and by a virus neutralization test. The ELISA results indicated that the E2s-C3d protein is 10,000-fold more immunogenic than the E2s protein alone. The maximum primary immune response was elicited with <0.1 microg of E2s-C3d protein without an adjuvant. In addition, we have shown for the first time that high levels of anti-E2s and neutralizing antibodies can be elicited when this same low concentration of E2s-C3d is used to both prime and boost the immune response. We conclude that the E2s-C3d fusion protein has significant potential as a subunit vaccine against BVDV infection.

Animals↗
PubMed2005

Immunogenicity of heterologous prime-boost regimens involving recombinant adenovirus serotype 11 (Ad11) and Ad35 vaccine vectors in the presence of anti-ad5 immunity.

The high prevalence of preexisting immunity to adenovirus serotype 5 (Ad5) in human populations will likely limit the immunogenicity and clinical utility of recombinant Ad5 (rAd5) vector-based vaccines for human immunodeficiency virus type 1 and other pathogens. A potential solution to this problem is to utilize rAd vaccine vectors derived from rare Ad serotypes such as Ad35 and Ad11. We have previously reported that rAd35 vectors were immunogenic in the presence of anti-Ad5 immunity, but the immunogenicity of heterologous rAd prime-boost regimens and the extent that cross-reactive anti-vector immunity may limit this approach have not been fully explored. Here we assess the immunogenicity of heterologous vaccine regimens involving rAd5, rAd35, and novel rAd11 vectors expressing simian immunodeficiency virus Gag in mice both with and without anti-Ad5 immunity. Heterologous rAd prime-boost regimens proved significantly more immunogenic than homologous regimens, as expected. Importantly, all regimens that included rAd5 were markedly suppressed by anti-Ad5 immunity. In contrast, rAd35-rAd11 and rAd11-rAd35 regimens elicited high-frequency immune responses both in the presence and in the absence of anti-Ad5 immunity, although we also detected clear cross-reactive Ad35/Ad11-specific humoral and cellular immune responses. Nevertheless, these data suggest the potential utility of heterologous rAd prime-boost vaccine regimens using vectors derived from rare human Ad serotypes.

Adenoviruses, Human↗
PubMed2005

Comparative antigenicity and immunogenicity of hepadnavirus core proteins.

The hepatitis B virus core protein (HBcAg) is a uniquely immunogenic particulate antigen and as such has been used as a vaccine carrier platform. The use of other hepadnavirus core proteins as vaccine carriers has not been explored. To determine whether the rodent hepadnavirus core proteins derived from the woodchuck (WHcAg), ground squirrel (GScAg), and arctic squirrel (AScAg) viruses possess immunogen characteristics similar to those of HBcAg, comparative antigenicity and immunogenicity studies were performed. The results indicate that (i) the rodent core proteins are equal in immunogenicity to or more immunogenic than HBcAg at the B-cell and T-cell levels; (ii) major histocompatibility complex (MHC) genes influence the immune response to the rodent core proteins (however, nonresponder haplotypes were not identified); (iii) WHcAg can behave as a T-cell-independent antigen in athymic mice; (iv) the rodent core proteins are not significantly cross-reactive with the HBcAg at the antibody level (however, the nonparticulate "eAgs" do appear to be cross-reactive); (v) the rodent core proteins are only partially cross-reactive with HBcAg at the CD4+ T-cell level, depending on MHC haplotype; and (vi) the rodent core proteins are competent to function as vaccine carrier platforms for heterologous, B-cell epitopes. These results have implications for the selection of an optimal hepadnavirus core protein for vaccine design, especially in view of the "preexisting" immunity problem that is inherent in the use of HBcAg for human vaccine development.

Amino Acid Sequence↗
PubMed1982

Immunogenicity of potassium thiocyanate extracted and electrofocused Pasteurella multocida X-73I antigens in chickens and mice.

The immunogenicity of antigenic fractions obtained by the extraction of Pasteurella multocida strain X-73 (serotype 1) with potassium thiocyanate (KSCN) was determined in chickens and mice. The initial KSCN extract was centrifuged at 105 000 X g, and the antigens were separated into a particulate fraction (40p) and a soluble supernatant fraction (40s). The ultracentrifuged fractions were further resolved by preparative electrofocusing. The 40p fraction was resolved into two subgroups having isoelectric points of 3.5-3.9 and 5.5-6.0; the 40s fraction was resolved into five subgroups ranging in isoelectric points from 4.4 to 9.0. The 40p fractions were antigenically similar and contained lipopolysaccharide (LPS) and protein. The 40s fractions were antigenically distinct from the 40p fractions and from each other; they contained proteins and polysaccharides but no LPS. The 40p antigens were strongly immunogenic in mice and chickens, whereas the 40s antigens were weakly immunogenic in chickens and not immunogenic in mice. The incorporation of Freund's complete adjuvant increased the immunogenicity of the 40s antigens in chickens. The 40p antigens induced greater frequencies of serological responses in chickens than the 40s antigens as detected by counterimmunoelectrophoresis and immunodiffusion. This suggested that the increased protection associated with the 40p antigens may have been the result of better antibody response. The toxicity of all the fractions was evaluated by determination of lethality for 10-day-old chicken embryos because of the sensitivity and reliability of the test. The 40p fraction had an LD50 = 0.38 micrograms, and the 40s fraction had an LD50 = 2.5 micrograms. Since the 40s fraction contained no detectable LPS, it is likely that two toxins are present, one which contains LPS and one which does not.

Adjuvants, Immunologic↗
PubMed2000

Immunogenicity of antigens in boiled alginate microspheres.

Vaccine efficacy can be enhanced by delivery of antigens in synthetic microspheres. The process of antigen incorporation into microspheres can expose fragile antigens to damaging conditions, such as high temperatures, and to bacterial contamination. Maintenance of immunogenicity of several antigens and reduction of bacterial load in alginate microspheres following boiling was evaluated. Mice were immunized subcutaneously, initially and again 21 days later, with either non-boiled or boiled microspheres containing ovalbumin (OVA), a culture supernatant vaccine of Pasteurella haemolytica (PHV), or a potassium thiocyanate extract of P. multocida (PTE). Serum samples were obtained prior to immunization and at the time of euthanasia 28 days later. Culture of microspheres showed that boiling completely eliminated aerobic bacterial growth for OVA-containing microspheres, and reduced growth by a factor of 10(4) for PTE microspheres. More bacteria were cultured after boiling than before for PHV microspheres. ELISA performed on serum and intestinal lamina propria explant supernatants showed that immunogenicity of PHV microspheres was not altered by boiling. Boiled OVA microspheres were still able to stimulate a significant serum IgG anti-OVA titer in mice, but boiled PTE microspheres completely lacked immunogenicity. Elispot assays of spleens showed that only PHV microspheres were able to retain immunogenicity after boiling. Results indicate that boiling is not an effective means for reducing the bacterial load of alginate microspheres and that the process is associated with a diminution of vaccine immunogenicity.

Alginates↗
PubMed1992

Effects of chain length on the immunogenicity in rabbits of group B Streptococcus type III oligosaccharide-tetanus toxoid conjugates.

One method to improve the immunogenicity of polysaccharide antigens is the covalent coupling of the native polysaccharide or a derivative oligosaccharide to a carrier protein. In general, T cell-dependent properties are enhanced in conjugates of smaller saccharides, but a conformational epitope of the native polysaccharide may be better expressed in conjugates of larger saccharides. We have reported previously the synthesis and immunogenicity in animals of an oligosaccharide-tetanus toxoid conjugate vaccine against type III group B Streptococcus. In this study, we sought to determine the optimal size of group B Streptococcus type III oligosaccharide for use in a conjugate vaccine by evaluating the relative immunogenicity of conjugate vaccines containing oligosaccharides that were twofold smaller (7,000 Mr) or larger (27,000 Mr) than that reported previously (14,500 Mr). All three type III oligosaccharide conjugate vaccines were immunogenic in rabbits, in contrast to native, uncoupled group B Streptococcus type III polysaccharide. However, with respect to eliciting specific antibodies that were protective in vivo, the vaccine containing the intermediate-size oligosaccharide was superior to the smaller or larger conjugate vaccine. Analysis of opsonic activity of vaccine-induced antibodies demonstrated a predominance of IgG antibodies, thought to reflect T cell dependence, in response to shorter chain length conjugates, while the conformational epitope of the native polysaccharide was maximally expressed on longer chain length conjugates. These opposing trends may account for the optimal immunogenicity of an intermediate-size group B Streptococcus type III oligosaccharide conjugate vaccine.

Animals↗
PubMedDate not supplied

Tumor immunogenicity--the prime determinant of the nutritional influence on the host-tumor relationship.

The influence which malnutrition plays on the host-tumor relationship is controversial because of the disparity of human and rodent tumors, a critical difference being the minimal immunogenicity of human tumors and the variable antigenicity of rodent tumors. The hypothesis we tested is that the influence of malnutrition on tumor growth is a result of the immunogenicity of the host's tumor. C-1300 neuroblastoma (NB) is an immunogenic tumor by in vivo and in vitro assessment while the histologically identical TBJ-NB clone is non-immunizing. Isogeneic A/J mice were malnourished with 2.5% protein chow and were inoculated with C-1300-NB or TBJ-NB; either serial tumor volumes were assessed by three-dimensional measurement or animals were serially killed and tumor weight/carcass weight ratios (TW/CW) were calculated. Non-immunogenic TBJ-NB grew more rapidly than C-1300-NB in both control and malnourished groups, but there was no difference in either tumor size or TW/CW ratios between the two TBJ-NB nutritional groups. Contrasting with these data were immunogenic C-1300-NB in that the tumor grew significantly better in malnourished mice (tumor volume p less than 0.05 day 12 and 14; TW/CW p less than 0.026 by day 21). Prior whole-body irradiation abrogated this difference. These data demonstrate that for tumors differing only in antigenicity the influence of malnutrition is on that tumor which induces an immunologic antitumor response.

Animals↗
PubMed2004

Field challenge of cattle vaccinated with a combined Babesia bovis and Babesia bigemina frozen immunogen.

To determine the optimal dose of a combined, frozen immunogen containing in vitro culture-derived strains of Babesia bovis and Babesia bigemina, twenty-four 14-month-old Bos taurus steers from a Boophilus microplus-free area in Northern Mexico were used in this experiment. Cattle were randomly allocated into six groups with four animals each, and were intramuscularly inoculated as follows: group 1 (control animals) were administered with normal bovine erythrocytes; group 2 received 1 x 10(7) B. bovis- and B. bigemina-infected erythrocytes as a combined fresh immunogen. Groups 3-6 were inoculated with a combined frozen immunogen containing (previous to cryopreservation at -196 degrees C) 1 x 10(7), 5 x 10(7), 1 x 10(8), and 5 x 10(8) infected erythrocytes of each parasite species, respectively. Four months after immunization, principal and control animals were translocated to a bovine babesiosis endemic zone for field challenge. This was carried out by introducing the experimental cattle to tick-infested pastures for 30 days without ixodicide treatment. Cattle were monitored from day 8 postintroduction to the field (PIF) by recording the manifestation of clinical disease, rectal temperature values (RT), packed cell volume index (PCV), and percent of parasitized erythrocytes (PPE). At challenge, all experimental cattle became infected with both Babesia bovis and B. bigemina. However, except for two animals from group 6, none of the vaccinated animals showed signs of acute clinical babesiosis; therefore, no treatment was instituted. Out of six animals showing acute clinical babesiosis (four group 1 controls and two group 6 vaccinates), two animals (one from each group) died, despite babesiacide treatment, as they manifested classical cerebral babesiosis caused by B. bovis. Regardless of the dose or type of immunogen used (combined fresh or frozen), 90% of vaccinated cattle were determined to be protected against the virulent Babesia sp. field isolates. Nevertheless, by evaluating clinical parameters, such as average of maximum drop in PVC index (28.5%), average duration of parasitemia (3 days for B. bovis; 8.5 days for B. bigemina), and average duration of RT values > or = 39.5 degrees C (2 days), animals receiving 1 x 10(8) infected erythrocytes, as combined frozen immunogen, were more efficaciously protected against challenge with virulent B. bovis and B. bigemina field isolates.

Animals↗