scholarly journals THE USE OF ADJUVANTS IN STUDIES ON INFLUENZA IMMUNIZATION

1952 ◽  
Vol 95 (5) ◽  
pp. 429-447 ◽  
Author(s):  
Jonas E. Salk ◽  
Angela M. Laurent
Keyword(s):  
Influenza Virus ◽  
Antibody Response ◽  
Antibody Formation ◽  
Careful Analysis ◽  
Antibody Responses ◽  
Adjuvant Effect ◽  
Oil Emulsion ◽  
Water In Oil Emulsion ◽  
The Relationship ◽  
Induce Antibody

Untoward reactions at the site of inoculation were not observed in monkeys vaccinated with influenza virus incorporated in a water-in-oil emulsion without acid-fast bacilli. Studies were then made to measure some of the dimensions of antigenicity of these emulsions to evaluate the extent of the immunologic adjuvant effect. This included measurements of height and persistence of the antibody response to inoculation and measurements of the extent to which the vaccine could be diluted and still induce antibody formation; i.e., antigenic extinction. In addition, comparisons were made of the rates of development of hemagglutination-inhibiting, virus-neutralizing, and complement-fixing antibody activities to determine the relationship among these three properties of the serum of immunized animals. It was found that levels of antibody many fold higher were induced by the virus-adjuvant mixtures as compared with virus in an aqueous menstruum, and that the level of antibody induced was related to the quantity of antigen incorporated in the emulsion. The stock vaccine when emulsified could be diluted 100,000-fold and was still active in antibody formation whereas a 100-fold dilution of the antigen without emulsification was essentially ineffective. Equivalent quantities of virus in 0.1 ml. or 1.0 ml. of emulsion induced antibody responses that were indistinguishable with respect to level or persistence. In comparing the course of antibody development it was found that hemagglutination-inhibiting, virus-neutralizing, and complement-fixing antibodies develop at different rates; careful analysis of the data derived from the present study together with other observations warrant the conclusion that these antibody activities are not present in constant proportion and are independent of one another. The implications of this observation and of the others mentioned above are discussed.

scholarly journals SARS-CoV-2 IgG antibody responses in rt-PCR positive cases: first report from India

2020 ◽  
Author(s):  
Girish Chandra Dash ◽  
Debaprasad Parai ◽  
Hari Ram Choudhary ◽  
Annalisha Peter ◽  
Usha Kiran Rout ◽  
...  
Keyword(s):  
Antibody Response ◽  
Infected Individual ◽  
Antibody Responses ◽  
Rt Pcr ◽  
Serum Samples ◽  
Igg Antibody ◽  
Ct Value ◽  
Significant Difference ◽  
The Mean ◽  
The Relationship

AbstractThe SARS-CoV-2 antibody responses remain poorly understood and the clinical utility of serological testing is still unclear. As it is thought to confer some degree of immunity, this study is carried out to know the relationship between demographics and ct value of confirmed rt-PCR patients. A total of 384 serum samples were collected between 4-6 weeks after confirmed SARS-CoV-2 infection. IgG positivity was found to be 80.2% (95% CI, 76.2 – 84.2). The IgG positivity increased with the decrease in the ct value, with highest of 87.6% positivity in individuals with <20 ct value. The mean (± SD) ct value of IgG positives and og IgG negatives was 23.34 (± 6.09) and 26.72 (± 7.031) respectively. There was no significant difference found between the demographic characteristics such as age, sex, symptoms and antibody response. The current study is first of its kind wherein we have assessed the correlation of ct of RT-PCR with development of IgG against SARS-CoV-2. Our study showed that although Ct value might not have any relation with severity of the diseases but is associated with the antibody response among the SARS-CoV-2 infected individual.

scholarly journals Comparison of Complement Fixation and Hemagglutination Inhibition Assays for Detecting Antibody Responses following Influenza Virus Vaccination

2003 ◽  
Vol 10 (3) ◽  
pp. 481-482 ◽  
Author(s):  
Harry E. Prince ◽  
Amy L. Leber
Keyword(s):  
Influenza Virus ◽  
Antibody Response ◽  
Hemagglutination Inhibition ◽  
Complement Fixation ◽  
Antibody Responses ◽  
Virus Vaccination ◽  
Virus Antigens ◽  
Low Sensitivity

ABSTRACT Complement fixation (CF) was compared to hemagglutination inhibition (HI) as a method for identifying antibody responses to influenza virus vaccination. CF assays were performed at two different laboratories using paired (pre- and postvaccination) sera from 38 vaccinated laboratory employees; HI assays were performed at a third laboratory. As expected, most vaccinees (31/38 = 82%) responded to at least one of three influenza virus antigens as measured by HI. In contrast, only 21% (8/38) of vaccinees showed a response by CF at laboratory 1, and only 29% (11/38) showed a response by CF at laboratory 2. These findings indicate that due to low sensitivity, CF assays should not be used to assess the antibody response to influenza virus vaccination.

scholarly journals THE ANTIBODY RESPONSE IN RABBITS TO KILLED SUSPENSIONS OF PATHOGENIC T. PALLIDUM

1948 ◽  
Vol 87 (5) ◽  
pp. 369-384 ◽  
Author(s):  
Harry Eagle ◽  
Ralph Fleischman
Keyword(s):  
Antibody Response ◽  
Intravenous Injection ◽  
Complement Fixation ◽  
Specific Antigen ◽  
Mammalian Tissue ◽  
Oil Emulsion ◽  
Specific Antibodies ◽  
Aqueous Suspensions ◽  
Living Organisms ◽  
Water In Oil Emulsion

The intravenous injection into rabbits of suspensions of dead T. pallidum derived from rabbit testicular chancres regularly caused the appearance of Wassermann and flocculation antibodies in significantly increased titer. Control suspensions of cultured treponemes (Reiter strain) added to extracts of normal testes were ineffective. This suggests that the Wassermann and flocculation reagin elaborated during syphilitic infection may be an antibody to T. pallidum which happens to cross-react with alcoholic extracts of mammalian tissue. The antisera did not cause the agglutination of suspensions of pathogenic T. pallidum, living or dead, did not give specific complement fixation with those suspensions, and did not usually cause the living treponemata to lose their infectiousness. Animals immunized with such aqueous suspensions for as long as 4 months, or with organisms suspended in a water-in-oil emulsion, were not demonstrably resistant to infection. As few as ten living organisms inoculated intradermally into animals "immunized" with as many as 38 billion dead treponemata regularly produced typical darkfield positive infections; and two of five animals inoculated intratesticularly with ten organisms were also infected. The contradiction involved in the production of antibodies cross-reacting with a non-specific antigen, and the non-appearance of specific antibodies against the organism used as antigen, is discussed in the text.

Adjuvant effect of low-dose interleukin-2 on antibody response to influenza virus vaccination in healthy elderly subjects

1994 ◽  
Vol 77 (2) ◽  
pp. 75-82 ◽  
Author(s):  
Mauro Provinciali ◽  
Giuseppina Di Stefano ◽  
Mauro Colombo ◽  
Francesco Della Croce ◽  
Maria Carla Gandolfi ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Antibody Response ◽  
Low Dose ◽  
Interleukin 2 ◽  
Elderly Subjects ◽  
Adjuvant Effect ◽  
Virus Vaccination ◽  
Healthy Elderly ◽  
Healthy Elderly Subjects

scholarly journals Sera from Individuals with Narrowly Focused Influenza Virus Antibodies Rapidly Select Viral Escape MutationsIn Ovo

2018 ◽  
Vol 92 (19) ◽  
Author(s):  
Amy K. F. Davis ◽  
Kevin McCormick ◽  
Megan E. Gumina ◽  
Joshua G. Petrie ◽  
Emily T. Martin ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Influenza Virus ◽  
Monoclonal Antibodies ◽  
Antibody Response ◽  
Antigenic Site ◽  
Influenza Viruses ◽  
Antibody Responses ◽  
Host Cells ◽  
Viral Escape ◽  
In Ovo

ABSTRACTInfluenza viruses use distinct antibody escape mechanisms depending on the overall complexity of the antibody response that is encountered. When grown in the presence of a hemagglutinin (HA) monoclonal antibody, influenza viruses typically acquire a single HA mutation that reduces the binding of that specific monoclonal antibody. In contrast, when confronted with mixtures of HA monoclonal antibodies or polyclonal sera that have antibodies that bind several HA epitopes, influenza viruses acquire mutations that increase HA binding to host cells. Recent data from our laboratory and others suggest that some humans possess antibodies that are narrowly focused on HA epitopes that were present in influenza virus strains that they were likely exposed to in childhood. Here, we completed a series of experiments to determine if humans with narrowly focused HA antibody responses are able to select for influenza virus antigenic escape variantsin ovo. We identified three human donors that possessed HA antibody responses that were heavily focused on a single HA antigenic site. Sera from all three of these donors selected single HA escape mutations duringin ovopassage experiments, similar to what has been previously reported for single monoclonal antibodies. These single HA mutations directly reduced binding of serum antibodies used for selection. We propose that new antigenic variants of influenza viruses might originate in individuals who produce antibodies that are narrowly focused on HA epitopes that were present in viral strains that they encountered in childhood.IMPORTANCEInfluenza vaccine strains must be updated frequently since circulating viral strains continuously change in antigenically important epitopes. Our previous studies have demonstrated that some individuals possess antibody responses that are narrowly focused on epitopes that were present in viral strains that they encountered during childhood. Here, we show that influenza viruses rapidly escape this type of polyclonal antibody response when grownin ovoby acquiring single mutations that directly prevent antibody binding. These studies improve our understanding of how influenza viruses evolve when confronted with narrowly focused polyclonal human antibodies.

scholarly journals Antibody response and reactions to aqueous influenza vaccine, simple emulsion vaccine and multiple emulsion vaccine. A report to the Medical Research Council Committee on influenza and other respiratory virus vaccines

1969 ◽  
Vol 67 (3) ◽  
pp. 485-490 ◽  
Author(s):  
P. J. Taylor ◽  
Christine L. Miller ◽  
T. M. Pollock ◽  
F. T. Perkins ◽  
M. A. Westwood
Keyword(s):  
Antibody Response ◽  
Influenza Vaccine ◽  
Medical Research ◽  
Research Council ◽  
Medical Research Council ◽  
Mineral Oil ◽  
Multiple Emulsion ◽  
Water Emulsion ◽  
Oil Emulsion ◽  
Water In Oil Emulsion

Influenza vaccines prepared with a mineral oil adjuvant induce a substantial and durable antibody response. However, vaccines containing mineral oil in simple emulsion (water-in-oil emulsion) sometimes produce persistent local reactions (Medical Research Council, 1964). The development of a redispersed ‘multiple’ emulsion in which antigen is incorporated as an oil-in-water emulsion starting from an original water-in-oil emulsion was described by Herbert (1965). Such multiple emulsion vaccine has a lesser viscosity than simple emulsions and might therefore produce a substantial antibody response with fewer reactions. In this investigation a comparison has been made of the antibody response and short-term vaccination reactions after aqueous influenza vaccine, influenza vaccine containing a mineral oil in simple emulsion, and influenza vaccine containing mineral oil in multiple emulsion.

scholarly journals ADJUVANTS IN IMMUNIZATION WITH INFLUENZA VIRUS VACCINES

1944 ◽  
Vol 80 (6) ◽  
pp. 477-491 ◽  
Author(s):  
William F. Friedewald
Keyword(s):  
Influenza Virus ◽  
High Speed ◽  
Allantoic Fluid ◽  
Sesame Oil ◽  
Oil Emulsion ◽  
Paraffin Oil ◽  
Antigenic Material ◽  
Water In Oil Emulsion ◽  
Antibody Levels ◽  
Subcutaneous Inoculation

Subcutaneous inoculation, of PR8 allantoic fluid, or watery suspensions of the virus obtained from allantoic fluid by high-speed centrifugation or by elution after adsorption on red cells induced serum antibodies in experimental animals, which reached the highest levels within 2 weeks after inoculation and were gradually lost thereafter. The addition of killed acid-fast bacteria (Myco. tuberculosis or butyricum), paraffin oil, and a proprietary adsorption base (Falba) to form a stable water-in-oil emulsion of influenza virus suspensions greatly enhanced and maintained immunity and antibody response to the virus. These adjuvants provided a much more effective method of increasing antibody production to the virus than the use of concentrated preparations of virus alone. Paraffin oil and Falba without the acid-fast bacilli were less effective as adjuvants, although the antibody levels induced were higher than those produced by watery suspensions of the virus and were maintained at a constant level for at least 6 months. Myco. butyricum appeared to be more effective in producing antibodies against the virus than the tubercle bacilli in the emulsions of paraffin oil and Falba. Immunization with these adjuvants and suspensions of influenza virus obtained from allantoic fluid induced antibodies not only against the virus but against antigenic material contained in normal allantoic fluid, although the latter titers were considerably lower. A suspension of influenza virus (sedimented by high-speed centrifugation) and Myco. butyricum in sesame oil induced about four times as much antibody as when the virus was suspended in saline, in sesame oil alone, or in combination with typhoid bacilli.

scholarly journals SARS-CoV-2 IgG antibody responses in rt-PCR-positive cases: first report from India

2021 ◽  
Vol 3 (10) ◽  
Author(s):  
Girish Chandra Dash ◽  
Debaprasad Parai ◽  
Hari Ram Choudhary ◽  
Annalisha Peter ◽  
Usha Kiran Rout ◽  
...  
Keyword(s):  
Antibody Response ◽  
Clinical Utility ◽  
Antibody Responses ◽  
Serological Testing ◽  
Rt Pcr ◽  
Serum Samples ◽  
Igg Antibody ◽  
Significant Difference ◽  
The Mean ◽  
The Relationship

Introduction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody responses remain poorly understood and the clinical utility of serological testing is still unclear. Aim. To understand the relationship between the antibody response to SARS-CoV-2 infection and the demographics and cycle threshold (C t) values of confirmed RT-PCR patients. Methodology. A total of 384 serum samples were collected from individuals between 4–6 weeks after confirmed SARS-CoV-2 infection and tested for the development of immunoglobulin class G (IgG) against SARS-CoV-2. The C t values, age, gender and symptoms of the patients were correlated with the development of antibodies. Results. IgG positivity was found to be 80.2 % (95 % CI, 76.2–84.2). Positivity increased with a decrease in the C t value, with the highest (87.6 %) positivity observed in individuals with C t values <20. The mean (±sd) C t values for IgG positives and negatives were 23.34 (±6.09) and 26.72 (±7.031), respectively. No significant difference was found for demographic characteristics such as age and sex and symptoms and antibody response. The current study is the first of its kind wherein we have assessed the correlation of the RT-PCR C t with the development of IgG against SARS-CoV-2. Conclusion. Although C t values might not have any relation with the development of symptoms, they are associated with the antibody response among SARS-CoV-2-infected individuals.

scholarly journals Original antigenic sin priming of influenza virus hemagglutinin stalk antibodies

2020 ◽  
Vol 117 (29) ◽  
pp. 17221-17227 ◽  
Author(s):  
Claudia P. Arevalo ◽  
Valerie Le Sage ◽  
Marcus J. Bolton ◽  
Theresa Eilola ◽  
Jennifer E. Jones ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Antibody Response ◽  
Influenza A ◽  
Influenza Viruses ◽  
Antibody Responses ◽  
Virus Infections ◽  
Universal Vaccine ◽  
Influenza Virus Hemagglutinin ◽  
Stalk Domain ◽  
Original Antigenic Sin

Immunity to influenza viruses can be long-lived, but reinfections with antigenically distinct viral strains and subtypes are common. Reinfections can boost antibody responses against viral strains first encountered in childhood through a process termed “original antigenic sin.” It is unknown how initial childhood exposures affect the induction of antibodies against the hemagglutinin (HA) stalk domain of influenza viruses. This is an important consideration since broadly reactive HA stalk antibodies can protect against infection, and universal vaccine platforms are being developed to induce these antibodies. Here we show that experimentally infected ferrets and naturally infected humans establish strong “immunological imprints” against HA stalk antigens first encountered during primary influenza virus infections. We found that HA stalk antibodies are surprisingly boosted upon subsequent infections with antigenically distinct influenza A virus subtypes. Paradoxically, these heterosubtypic-boosted HA stalk antibodies do not bind efficiently to the boosting influenza virus strain. Our results demonstrate that an individual’s HA stalk antibody response is dependent on the specific subtype of influenza virus that they first encounter early in life. We propose that humans are susceptible to heterosubtypic influenza virus infections later in life since these viruses boost HA stalk antibodies that do not bind efficiently to the boosting antigen.

THE HEMAGGLUTINATION REACTION TO BCG AND VOLE BACILLUS VACCINATIONS

1954 ◽  
Vol 1 (1) ◽  
pp. 79-84
Author(s):  
Roma Z. Hawirko
Keyword(s):  
Antibody Response ◽  
Standard Procedure ◽  
Control Series ◽  
Oil Emulsion ◽  
Bcg Vaccination ◽  
The Third ◽  
Fourth Series ◽  
In Series ◽  
Water In Oil Emulsion

The antibody response in four groups of five rabbits, three vaccinated with BCG and one with the vole bacillus, was measured by the hemagglutination reaction. In the control series, in which the standard BCG vaccination procedure was carried out, a mean titer of 1:16 or higher appeared on the third week and was maintained for eight weeks. In the second series, in which the vaccine was administered in two doses, with a three-week interval, a titer of 1:16 or higher appeared on the fourth week and was maintained for 11 weeks. In the third series the vaccine was prepared in a water-in-oil emulsion and administered as in the control series. A titer of 1:16 or higher appeared on the second week and was maintained for 13 weeks. In the fourth series the standard procedure was followed, except that the vole bacillus was substituted for BCG. A titer of 1:16 appeared on the fifth week and was maintained for three weeks. The differences between the results in series three and in series four and those of the control were significant, whereas the results in series two did not differ significantly from those of the control.

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