Passive Transfer Of Antisera Research Articles

KbvR mutant of Klebsiella pneumoniae affects the synthesis of type 1 fimbriae and provides protection to mice as a live attenuated vaccine

Klebsiella pneumoniae is a leading cause of severe infections in humans and animals, and the emergence of multidrug-resistant strains highlights the need to develop effective vaccines for preventing such infections. Live attenuated vaccines are attractive vaccine candidates available in the veterinary field. We recently characterized that the K. pneumoniae kbvR (Klebsiella biofilm and virulence regulator) mutant was a highly attenuated strain in the mice model. In the present study, the characterization, safety, and protective efficacy of ΔkbvR strain as a live attenuated vaccine were evaluated. The synthesis and activity of type 1 fimbriae were increased in the ΔkbvR strain. All mice inoculated by the subcutaneous route with 105, 106, and 107 colony-forming units (CFU) doses of the ΔkbvR strain survived. Subcutaneous immunization with two doses of 105 or 107 CFU ΔkbvR elicited a robust humoral immune response, and provided protection against the following K. pneumoniae intraperitoneal infection. The antisera of mice immunized with 105 CFU dose improved the opsonophagocytic ability and complement-mediated lysis not only to the same serotype strain but also to the different serotype strain. The passive transfer of antisera from 105 CFU dose-immunized mice provided protection against K. pneumoniae infection. Overall, our results suggest the great potential of the ΔkbvR strain as a novel vaccine candidate against K. pneumoniae infections in herds or humans.

Effect of Immune Responses Against Hydatid Cyst Antigens on Growth of Melanoma Tumor

Background: Hydatid cyst is the larval stage of the tape worm parasite, Echinococcus granulosus. Human is infected by ingestion of parasite ova excreted in dog feces. The anticancer activity of different antigens of hydatid cyst has been reported in the previous works. In this research, the role of immune system in induction of this anticancer activity has been investigated.Materials and Methods: Spleen cells of mice immunized with hydatid cyst antigens were transferred to the recipient mice that had already been challenged with melanoma cells. Also, mice with melanoma cancer were injected with antisera raised against hydatid cyst antigens. In all above mice, tumor growth was measured using a caliper. Results: Passive transfer of spleen cells resulted in significant inhibition of melanoma cancer growth. However passive transfer of antisera did not affect cancer growth in the recipient mice.Conclusion: According to the results of this work, cellular immunity but not humoral immunity may be involved in induction of anticancer activities of hydatid cyst.

Immunogenicity and protective efficacy of monovalent PCVs containing 22F and 33F polysaccharides in mouse models of colonization and co-infection

BackgroundIn the current transmission, we studied the immunogenicity and protective efficacy of serotypes 22F and 33F in the prevention of colonization and of invasive Streptococcus pneumoniae (Spn) pathogenesis during an influenza co-infection. Serotypes 22F and 33F are emerging Spn serotypes, which are not part of currently administered pneumococcal conjugate vaccine formulations (PCVs). Spn serotype 6A is an ingredient in the currently administered PCV13 vaccine and was therefore included in the study as a control. MethodsAdult (six weeks) and infant (two weeks) C57BL/6 mice were intranasally infected in the nasopharynx (NP) with Spn serotypes 22F, 33F, or 6A. Influenza A H1N1 A/Puerto Rico/8/193 virus (PR8) was introduced one day after the NP Spn colonization. In an immunization challenge study, mice were vaccinated with monovalent 22F, 33F, or 6A polysaccharide conjugated to the CRM197 antigen. The immunized mice were colonized or co-infected to study the vaccines efficacy. ResultsAll three Spn serotypes established colonization in adult and infant mice. The co-infected mice showed an increase in Spn NP density. Invasive Spn infection (bacteremia) was observed following the co-infection with serotypes 22F and 6A but not 33F in adult mice, whereas infant mice developed bacteremia following co-infection with all three Spn serotypes. The vaccinations led to robust serum antibody responses to capsular polysaccharides 22F, 6A, and less for 33F. The vaccinations resulted in reductions of Spn NP colonization density for all three serotypes, prevention of bacteremia, and increased survival with Spn serotypes 22F and 6A. Passive transfer of antisera was associated with a reduction of Spn colonization densities in infant mice. ConclusionVaccinations with monovalent 22F, 33F, or 6A formulations protect against Spn colonization, and the efficacy of the 22F vaccination was comparable to the 6A vaccination in preventing an invasive Spn bacterial infection during an influenza co-infection.

Protection against Streptococcus pneumoniae Invasive Pathogenesis by a Protein-Based Vaccine Is Achieved by Suppression of Nasopharyngeal Bacterial Density during Influenza A Virus Coinfection.

An increase in Streptococcus pneumoniae nasopharynx (NP) colonization density during a viral coinfection initiates pathogenesis. To mimic natural S. pneumoniae pathogenesis, we commensally colonized the NPs of adult C57BL/6 mice with S. pneumoniae serotype (ST) 6A or 8 and then coinfected them with mouse-adapted H1N1 influenza A virus (PR/8/34). S. pneumoniae established effective commensal colonization, and influenza virus coinfection caused S. pneumoniae NP density to increase, resulting in bacteremia and mortality. We then studied histidine triad protein D (PhtD), an S. pneumoniae adhesin vaccine candidate, for its ability to prevent invasive S. pneumoniae disease in adult and infant mice. In adult mice, the efficacy of PhtD vaccination was compared with that of PCV13. Vaccination with PCV13 led to a greater reduction of S. pneumoniae NP density (>2.5 log units) than PhtD vaccination (∼1-log-unit reduction). However, no significant difference was observed with regard to the prevention of S. pneumoniae bacteremia, and there was no difference in mortality. Depletion of CD4+ T cells in PhtD-vaccinated adult mice, but not PCV13-vaccinated mice, caused a loss of vaccine-induced protection. In infant mice, passive transfer of antisera or CD4+ T cells from PhtD-vaccinated adult mice led to a nonsignificant reduction in NP colonization density, whereas passive transfer of antisera and CD4+ T cells was needed to cause a significant reduction in NP colonization density. For the first time, these data show an outcome with regard to prevention of invasive S. pneumoniae pathogenesis with a protein vaccine similar to that which occurs with a glycoconjugate vaccine despite a less robust reduction in NP bacterial density.

Virus-like particle-based vaccine against coxsackievirus A6 protects mice against lethal infections

Coxsackievirus A6 (CA6) is emerging as one of the major causative agents of hand, foot, and mouth disease (HFMD) worldwide. However, no vaccine is currently available for preventing CA6 infection. Here, we report the development of a virus-like particle (VLP)-based recombinant vaccine for CA6. We produced CA6 VLPs in insect cells by infecting the cells with a baculovirus coexpressing the genes encoding CA6 P1 and 3CD. Biochemical analyses showed that the produced VLPs consisted of VP0, VP1, and VP3 capsid subunit proteins generated by the cleavage of P1 by 3CD. Mice immunized with these VLPs produced CA6-specific serum antibodies. Passive transfer of antisera from CA6 VLP-immunized mice protected recipient mice from lethal infections caused by homologous and heterologous CA6 strains. Moreover, active immunization of mice with CA6 VLPs efficiently conferred protection against both homologous and heterologous CA6 infections. These results suggested that CA6 VLP-based recombinant vaccine is a promising candidate vaccine for preventing CA6 infection and can be incorporated into a multivalent HFMD vaccine formulation to achieve broad-spectrum and effective prevention of this disease.

Antiserum from mice vaccinated with modified vaccinia Ankara virus expressing African horse sickness virus (AHSV) VP2 provides protection when it is administered 48 h before, or 48 h after challenge

Previous studies show that a recombinant modified vaccinia Ankara (MVA) virus expressing VP2 of AHSV serotype 4 (MVA-VP2) induced virus neutralising antibodies in horses and protected interferon alpha receptor gene knock-out mice (IFNAR −/−) against challenge. Follow up experiments indicated that passive transfer of antiserum, from MVA-VP2 immune donors to recipient mice 1h before challenge, conferred complete clinical protection and significantly reduced viraemia.These studies have been extended to determine the protective effect of MVA-VP2 vaccine-induced antiserum, when administered 48h before, or 48h after challenge. In addition, passive transfer of splenocytes was undertaken to assess if they confer any degree of immunity to immunologically naïve recipient mice. Thus, antisera and splenocytes were collected from groups of mice that had been vaccinated with MVA-VP2, or wild type MVA (MVA-wt), for passive immunisation of recipient mice. The latter were subsequently challenged with AHSV-4 (together with appropriate vaccinated or unvaccinated control animals) and protection was assessed by comparing clinical signs, lethality and viraemia between treated and control groups. All antiserum recipients showed high protection against disease (100% survival rates even in mice that were immunised 48h after challenge) and statistically significant reduction or viraemia in comparison with the control groups. The mouse group receiving splenocytes from MVA-VP2 vaccinates, showed only a 40% survival rate, with a small reduction in viraemia, compared to those mice that had received splenocytes from MVA-wt vaccinates. These results confirm the primarily humoral nature of protective immunity conferred by MVA-VP2 vaccination and show the potential of administering MVA-VP2 specific antiserum as an emergency treatment for AHSV.

Vaccination with DNA Plasmids Expressing Gn Coupled to C3d or Alphavirus Replicons Expressing Gn Protects Mice against Rift Valley Fever Virus

BackgroundRift Valley fever (RVF) is an arthropod-borne viral zoonosis. Rift Valley fever virus (RVFV) is an important biological threat with the potential to spread to new susceptible areas. In addition, it is a potential biowarfare agent.Methodology/Principal FindingsWe developed two potential vaccines, DNA plasmids and alphavirus replicons, expressing the Gn glycoprotein of RVFV alone or fused to three copies of complement protein, C3d. Each vaccine was administered to mice in an all DNA, all replicon, or a DNA prime/replicon boost strategy and both the humoral and cellular responses were assessed. DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn elicited high titer neutralizing antibodies that were similar to titers elicited by the live-attenuated MP12 virus. Mice vaccinated with an inactivated form of MP12 did elicit high titer antibodies, but these antibodies were unable to neutralize RVFV infection. However, only vaccine strategies incorporating alphavirus replicons elicited cellular responses to Gn. Both vaccines strategies completely prevented weight loss and morbidity and protected against lethal RVFV challenge. Passive transfer of antisera from vaccinated mice into naïve mice showed that both DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn elicited antibodies that protected mice as well as sera from mice immunized with MP12.Conclusion/SignificanceThese results show that both DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn administered alone or in a DNA prime/replicon boost strategy are effective RVFV vaccines. These vaccine strategies provide safer alternatives to using live-attenuated RVFV vaccines for human use.

Susceptibility of corneal allografts and xenografts to antibody-mediated rejection

The effects of passive transfer of antisera containing cytotoxic antibodies to allo- and xenoantigens on survival of corneal allografts and xenografts were evaluated in experimental models. Corneas from allogeneic B10 or xenogeneic rat Lewis donors were grafted orthotopically into BALB/c mice. Recipient mice were treated with donor-specific antisera administered at the period of grafting or at 2 weeks after transplantation. Rejection was determined by the severity of corneal opacity using a standard scoring system. Treatment of graft recipients with donor-specific antisera accelerated the onset of graft rejection and significantly shortened survival times of both corneal allografts and xenografts. Corneal xenografts, which had been accepted after treatment with anti-CD4 monoclonal antibody, were acutely rejected by the passive transfer of antiserum against xenoantigens. The results suggest that corneal grafts are vulnerable to antibody-dependent immunity and that cytotoxic antibodies against graft donor antigens can mediate rejection of both corneal allografts and xenografts.

Protective Antibody to Endotoxin Core: The Emperor's New Clothes?

Once upon a time, in one of Hans Christian Andersen's best-loved tales, there lived an emperor as gullible as he was vain. Out of fear for his reputation he engaged in temporary self-deception and dragged most of his subjects along with him. On parade one day in some new clothes, he began to shiver, and he finally was forced to accept the possibility, suggested by a child, that his much-admired costume was not real. Similar worries have plagued investigators who report that passive transfer of antisera to oligosaccharide-deficient (rough) endotoxin mutants results in protection against challenge with smooth gramnegative bacteria and their endotoxins (lipopolysaccharides [LPS]). The rationale for research on antibodies to endotoxin core is straightforward and can be summarized simply in the following set of hypotheses. Endotoxin is capable of initiating many of the biochemical abnormalities associated with death from gram-negative bacteremia. Although antibiotics are required to clear bacteremia, they do not reverse evolving shock, because endotoxin free in the bloodstream or exposed on the surface of circulating bacteria continues to activate mediators of cell damage until natural clearance and detoxification mechanisms in the host are able to handle the load. Therefore, strategies for immunologic intervention in gram-negative shock have been focused on the LPS molecule and on its core determinants in particular. Unlike the type-specific oligosaccharide side chains (O antigens), endotoxin core structures (core sugars and lipid A) seem highly conserved over the wide range of gram-negative genera pathogenic for humans. It was thought that these common determinants might stimulate widely cross-reactive antibodies to LPS that could function to augment natural host defenses and/or decrease biologically

The effect of antigenic strength and immunisation on the popliteal lymph node allograft response.

The kinetics of the popliteal lymph node response to an allograft of lymphoid cells injected into the foot pad were examined after challenge with strong (Ag-B) and weak (non Ag-B) transplantation antigens. The response to weak antigens was characterised by a lag period of 2 days. The response to strong antigens was more rapid in onset. Active immunisation against weak antigens accelerated the response so that it came to resemble the immediate response to strong antigens. Active immunisation against strong antigens depressed the response. This depression was reproduced by giving passive antiserum to normal recipients. Passive antiserum produced by immunisation against weak antigens was also suppressive. Adoptive transfer of immune lymphoid cells reproduced the effects seen with passive transfer of antiserum. These findings indicate that clonal expansion of antigen-sensitive cells is characteristic of immunity to weak and not to strong antigens and that antibody is produced in both situations and has a similar suppressive effect on the cell-mediated response in addition to its direct effect on the graft.

Immunologic Studies of Pancreas-Specific Isoantigens

Summary Rhesus monkeys immunized with pooled Rhesus monkey pancreas extract and Freund's complete adjuvant developed pancreas-specific isoantibodies, and the electrophoretic mobility of the isoantigens is similar to that described in rabbits. Passive transfer of antiserum or immune lymph node and spleen cells to recipients whose pancreas possessed the necessary isoantigens produced no histologic changes or functional alterations of the recipient's pancreas. Autoimmunization of rabbits with their own pancreas incorporated in Freund's complete adjuvant failed to elicit auto- or isoantibodies and the pancreas of these immunized animals were normal grossly and histologically. Immunofluorescent studies showed the rabbit pancreas isoantigens to be located in the cytoplasm of the apex of the acinar cells. The pancreas isoantigens of both rabbits and Rhesus monkeys were detected in pancreatic secretions.