scholarly journals DEVELOPMENT OF AGGLUTININS AND PROTECTIVE ANTIBODIES IN RABBITS, AFTER INHALATION OF TYPE II PNEUMOCOCCI

1930 ◽  
Vol 52 (2) ◽  
pp. 225-234 ◽  
Author(s):  
Ernest G. Stillman

1. Following repeated inhalations of the degenerated non-virulent "R" forms of Type II pneumococcus, no type specific antibodies can be demonstrated in the serum of rabbits. 2. Following repeated inhalations of slightly virulent Type II (SAv) pneumococci, only protective antibodies can be demonstrated in the serum of rabbits. 3. Following repeated inhalations of virulent Type II (Sv) pneumococci, agglutinins and protective antibodies can be demonstrated in the serum of rabbits. 4. Following repeated exposures of rabbits to inhalation of pneumococci, the type specific response, evidenced by type specific protective antibodies and agglutinins, varies in direct proportion to the virulence of the culture used.

1927 ◽  
Vol 46 (1) ◽  
pp. 101-111 ◽  
Author(s):  
Emidio L. Gaspari ◽  
William L. Fleming ◽  
James M. Neill

The loss of the specialized function of S production by Type II pneumococcus was accompanied by a loss of the antigenic properties involved in both active and passive protection of mice. Absorption of Type II serum with S-producing pneumococci removed all the protective antibodies, as well as the type-specific agglutinins and S precipitins. The same absorption treatment of the serum by non-S-producing pneumococci failed entirely to remove the type-specific antibodies and did not affect the protective value of the serum. Absorption with bacteria-free culture fluids containing the reactive carbohydrate removed the protective antibodies as completely as absorption with the whole bacterial cells of type-specific strains. The results taken as a whole indicate that the antibodies involved in the usual protection of mice against Type II pneumococci are closely related, if not identical, to the specific anticarbohydrate precipitin.


1932 ◽  
Vol 55 (6) ◽  
pp. 853-865 ◽  
Author(s):  
Maxwell Finland ◽  
W. D. Sutliff

The blood of 63 human subjects selected because of the absence of recent infections, was studied for its content of specific antibodies against virulent strains of Types I, II, and III pneumococci before and after intracutaneous injections of minute amounts of pneumococcus products. The simultaneous injection of the specific polysaccharides of all three types of pneumococci and of proteins and autolysates derived from Types I and II pneumococci was followed by the appearance or increase of pneumococcidal power in the whole defibrinated blood and, in most instances, by the appearance of mouse-protective antibodies and agglutinins for one or more types. A single intracutaneous injection of 0.01 mg. of the protein-free type-specific polysaccharide of either Type I, Type II, or Type III pneumococci or 4 similar daily injections was followed, in most of 29 subjects, by the appearance of antibodies against the homologous, but not against the heterologous type pneumococci. Some subjects showed a simultaneous lowering of a preexisting pneumococcidal power for heterologous or homologous types. A single intracutaneous injection of O.1 mg. of pneumococcus protein in 13 individuals was not followed by the appearance of specific antibodies to any appreciable degree. Single intracutaneous injections of small amounts of autolysates derived from virulent strains of Type I, II, or III pneumococci were followed in 11 subjects by a more or less general rise in the pneumococcidal power with the appearance of homologous type agglutinins and protective antibodies in about one-third of the subjects.


1930 ◽  
Vol 52 (2) ◽  
pp. 215-224 ◽  
Author(s):  
Ernest G. Stillman

1. The susceptibility of rabbits to inhalations of pneumococci varies in direct proportion to the virulence of the organism for rabbits. 2. When rabbits are exposed to a pneumococcus spray, irrespective of the virulence of the organism, the bacteria readily penetrate into the lower respiratory tract. 3. When rabbits are exposed to a spray of avirulent degenerated "R" form of pneumococcus, septicemia does not occur and pneumococci are seldom recovered from the liver, kidney or spleen. 4. When rabbits are exposed to a spray of slightly virulent Pneumococcus Type II (SAv) a non-fatal septicemia may occur and pneumococci may be recovered from the liver, kidney and spleen. 5. When rabbits are exposed to a spray of virulent Type II (Sv) pneumococci, septicemia may occur which in certain instances terminates fatally. Pneumococci may also be recovered from the liver, kidney and spleen.


1931 ◽  
Vol 54 (3) ◽  
pp. 437-447 ◽  
Author(s):  
Oswald T. Avery ◽  
Walther F. Goebel

1. Type-specific antipneumococcus immunity has been induced in rabbits by immunization with antigen prepared by combining a specific derivative of the capsular polysaccharide of Type III Pneumococcus with globulin from horse serum. 2. Rabbits immunized with this antigen acquire active immunity against infection with virulent Type III pneumococci. 3. The sera of the immune rabbits contain type-specific antibodies which precipitate the Type III capsular polysaccharide, agglutinate Type III pneumococci, and specifically protect mice against Type III infection. 4. The experimental data are discussed with reference to: (1) the concurrence in the immune sera of type-specific antibodies for Pneumococcus and precipitins for horse globulin; (2) the determining influence of the capsular polysaccharide on the specificity of the antigen as a whole; (3) the unity of the type-specific precipitins, agglutinins, and protective antibodies induced by a single component of the pneumococcus in chemical union with an unrelated, animal protein.


1931 ◽  
Vol 54 (3) ◽  
pp. 449-451 ◽  
Author(s):  
Ralph W. G. Wyckoff ◽  
Adrian L. Ter Louw

1. Type-specific antipneumococcus immunity has been induced in rabbits by immunization with antigen prepared by combining a specific derivative of the capsular polysaccharide of Type III Pneumococcus with globulin from horse serum. 2. Rabbits immunized with this antigen acquire active immunity against infection with virulent Type III pneumococci. 3. The sera of the immune rabbits contain type-specific antibodies which precipitate the Type III capsular polysaccharide, agglutinate Type III pneumococci, and specifically protect mice against Type III infection. 4. The experimental data are discussed with reference to: (1) the concurrence in the immune sera of type-specific antibodies for Pneumococcus and precipitins for horse globulin; (2) the determining influence of the capsular polysaccharide on the specificity of the antigen as a whole; (3) the unity of the type-specific precipitins, agglutinins, and protective antibodies induced by a single compo of the pneu mococcus in chemical union with an unrelated, animal protein.


1997 ◽  
Vol 16 (1) ◽  
pp. 29-39 ◽  
Author(s):  
Sergio A. Jimenez ◽  
Leena Ala-Kokko ◽  
Darwin J. Prockop ◽  
Carmen F. Merryman ◽  
Nora Shepard ◽  
...  

mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Mark J. Bailey ◽  
Felix Broecker ◽  
James Duehr ◽  
Fortuna Arumemi ◽  
Florian Krammer ◽  
...  

ABSTRACTZika virus is a mosquito-borne flavivirus which can cause severe disease in humans, including microcephaly and other congenital malformations in newborns and Guillain-Barré syndrome in adults. There are currently no approved prophylactics or therapeutics for Zika virus; the development of a safe and effective vaccine is an urgent priority. Preclinical studies suggest that the envelope glycoprotein can elicit potently neutralizing antibodies. However, such antibodies are implicated in the phenomenon of antibody-dependent enhancement of disease. We have previously shown that monoclonal antibodies targeting the Zika virus nonstructural NS1 protein are protective without inducing antibody-dependent enhancement of disease. Here, we investigated whether the NS1 protein itself is a viable vaccine target. Wild-type mice were vaccinated with an NS1-expressing DNA plasmid followed by two adjuvanted protein boosters, which elicited high antibody titers. Passive transfer of the immune sera was able to significantly protect STAT2 knockout mice against lethal challenge by Zika virus. In addition, long-lasting NS1-specific IgG responses were detected in serum samples from patients in either the acute or the convalescent phase of Zika virus infection. These NS1-specific antibodies were able to functionally engage Fcγ receptors. In contrast, envelope-specific antibodies did not activate Fc-mediated effector functions on infected cells. Our data suggest that the Zika virus NS1 protein, which is expressed on infected cells, is critical for Fc-dependent cell-mediated immunity. The present study demonstrates that the Zika virus NS1 protein is highly immunogenic and can elicit protective antibodies, underscoring its potential for an effective Zika virus vaccine.IMPORTANCEZika virus is a global public health threat that causes microcephaly and congenital malformations in newborns and Guillain-Barré syndrome in adults. Currently, no vaccines or treatments are available. While antibodies targeting the envelope glycoprotein can neutralize virus, they carry the risk of antibody-dependent enhancement of disease (ADE). In contrast, antibodies generated against the NS1 protein can be protective without eliciting ADE. The present study demonstrates the effectiveness of an NS1-based vaccine in eliciting high titers of protective antibodies against Zika virus disease in a mouse model. Sera generated by this vaccine can elicit Fc-mediated effector functions against Zika virus-infected cells. Lastly, we provide human data suggesting that the antibody response against the Zika virus NS1 protein is long-lasting and functionally active. Overall, our work will inform the development of a safe and effective Zika virus vaccine.


1994 ◽  
Vol 13 (8) ◽  
pp. 551-557 ◽  
Author(s):  
Nian Chen ◽  
Mark R. Bowles ◽  
Susan M. Pond

1 The herbicide, paraquat, is accumulated by the energy-dependent polyamine uptake pathway of alveolar type II cells. There it undergoes redox cycling that results in an amplified production of toxic reactive oxygen species and depletion of NADPH and other reducing equivalents. These processes account for the lung being the major target organ for paraquat toxicity. 2 We postulated that paraquat-specific antibodies would inhibit the uptake of the herbicide by type II cells and prevent its toxicity. Accordingly, we examined the effects of paraquat-specific monoclonal antibodies and Fab fragments on the uptake, efflux and cytotoxicity of 50 μM paraquat in suspensions of alveolar type II cells isolated from the rat. 3 The uptake of paraquat was linear over 40 min. Over this time, the uptake rate was inhibited significantly (% inhibition, 73-89) by IgG (25 or 50 μM) or Fab fragments (50 or 100 μM). 4 The apparent efflux rate of paraquat, studied over 16 h, was increased significantly from 0.12 h-1 for the control cells in medium to 0.17 h-1 by paraquat-specific Fab fragments but was unaffected by the specific IgG. 5 Cytotoxicity was determined by measuring the release of 51Cr from the cells. The cytotoxicity of 50 μM paraquat was decreased significantly (percent decrease, 56-80%) in the presence of specific antibodies. 6 These studies in vitro suggest some potential for immunotherapy in selected cases of paraquat poisoning.


2002 ◽  
Vol 195 (12) ◽  
pp. 1625-1633 ◽  
Author(s):  
Antonio Barragan ◽  
L. David Sibley

After oral ingestion, Toxoplasma gondii crosses the intestinal epithelium, disseminates into the deep tissues, and traverses biological barriers such as the placenta and the blood-brain barrier to reach sites where it causes severe pathology. To examine the cellular basis of these processes, migration of T. gondii was studied in vitro using polarized host cell monolayers and extracellular matrix. Transmigration required active parasite motility and the highly virulent type I strains consistently exhibited a superior migratory capacity than the nonvirulent type II and type III strains. Type I strain parasites also demonstrated a greater capacity for transmigration across mouse intestine ex vivo, and directly penetrated into the lamina propria and vascular endothelium. A subpopulation of virulent type I parasites exhibited a long distance migration (LDM) phenotype in vitro, that was not expressed by nonvirulent type II and type III strains. Cloning of parasites expressing the LDM phenotype resulted in substantial increase of migratory capacity in vitro and in vivo. The potential to up-regulate migratory capacity in T. gondii likely plays an important role in establishing new infections and in dissemination upon reactivation of chronic infections.


1935 ◽  
Vol 61 (4) ◽  
pp. 545-558 ◽  
Author(s):  
Geoffrey Rake

The investigation of this isolated epidemic of meningococcus meningitis at a C.C.C. camp gave an opportunity to examine the carrier state in contacts carrying what were presumably virulent epidemic strains of organisms. With the aid of Miller's technique for the enhancement of the demonstrable virulence of meningococci for mice, it proved possible to test the virulence of the carrier strains from Camp Rusk. These results were consistent despite the interval of from 3 to 4 weeks which intervened between the isolation of the strains and the virulence titrations. Type I strains were found to have a high virulence, while the virulence of Type II strains was moderately high but definitely less than that of the Type I, and atypical strains and strains of N. catarrhalis isolated from carriers showed a very low virulence. The question of the precise nature of the carrier state was investigated. No evidence has been obtained yet as to the existence of a relationship between pharyngitis, coryza or upper respiratory disease and the presence and degree of the carrier state. This is unlike the situation with regard to pneumococcus carriers. On the other hand, it has proved possible to demonstrate reactions within the body to the meningococci in the nasopharynx, consisting of the formation of agglutinins and protective antibodies in the blood serum. 32.3 per cent of Type I and 60 per cent of Type II carrier sera showed moderate or good agglutinins for homologous organisms and 80 per cent of Type I and 40 per cent of Type II sera showed moderate or good protective antibodies against virulent homologous strains. No idea could be obtained as to the relationship of the presence or absence and the degree of serological reaction and the duration of the carrier state.


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