scholarly journals Antibody response in non-haemorrhagic smallpox patients

1969 ◽  
Vol 67 (4) ◽  
pp. 609-618 ◽  
Author(s):  
A. W. Downie ◽  
L. St Vincent ◽  
L. Goldstein ◽  
A. R. Rao ◽  
C. H. Kempe
Keyword(s):  
Antibody Response ◽  
Neutralizing Antibodies ◽  
World Health ◽  
Agar Gel ◽  
Retrospective Diagnosis ◽  
Antibody Titres ◽  
Special Value ◽  
Materials Used ◽  
Health Organization ◽  
Exact Correlation

SUMMARYTwo hundred and sixteen sera from 151 patients suffering from smallpox (non-haemorrhagic) were examined for antibody by precipitation in agar gel, by haemagglutinin inhibition (HI), complement fixation (CF) and neutralization tests. Most of the patients were adults and the majority had been vaccinated earlier in life. HI and neutralizing antibodies showed rising titres from the 6th day of illness while the majority showed precipitins and CF antibodies from the 8th day. The results of the precipitation-in-agar-gel tests are in marked contrast to the findings in healthy vaccinated and revaccinated individuals, none of whose sera gave a positive result for antibody by this technique. In unvaccinated patients the antibody response was frequently delayed and the titres lower than those attained by the previously vaccinated patients. There was no exact correlation in antibody titres obtained by the four methods of measurement, HI antibody, in particular, reaching in some cases relatively high titres when other tests showed low titres. It is suggested that with the methods and materials used, a positive precipitation test in agar gel, a CF titre of 1/20 or more and an HI titre of 1/80 or higher in a single specimen of serum would be suggestive of recent smallpox infections. Such a result might be of special value in the retrospective diagnosis of missed cases and in the detection of minimal or subclinical infections.This investigation was supported in part by Public Health Service Grant AI–1632–16 VR from the National Institute of Allergy and Infectious Diseases, by the World Health Organization and by the Marcus T. Reynolds III Fund.

scholarly journals Haemorrhagic smallpox

1969 ◽  
Vol 67 (4) ◽  
pp. 619-629 ◽  
Author(s):  
A. W. Downie ◽  
D. S. Fedson ◽  
L. St Vincent ◽  
A. R. Rao ◽  
C. H. Kempe
Keyword(s):  
Neutralizing Antibodies ◽  
Public Health Service ◽  
Complement Fixation ◽  
World Health ◽  
Soluble Antigen ◽  
Type I ◽  
Type Ii ◽  
Fixation Technique ◽  
Agar Gel ◽  
Health Organization

SUMMARYIn practically all acute fulminating smallpox infections—haemorrhagic type I cases—there is severe viraemia with 104 or more infective particles of virus per ml. of blood. In most of these patients soluble antigen can be demonstrated in serum by precipitation in agar gel tests, or by the complement-fixation technique. In late haemorrhagic cases (type II) the degree of viraemia is less and soluble antigen is less often demonstrated in the blood. Five of forty type II patients recovered. The majority of the 77 patients studied were adults and bore scars of previous vaccination. Thirteen were pregnant women and 10 of these suffered from type I infections.The antibody response in patients who survived 6 days or longer as determined by the estimation of precipitins, CF antibodies and neutralizing antibodies in serum, was considerably less than that seen in non-haemorrhagic smallpox patients.In acute fulminating smallpox infections, the finding of virus or soluble antigen in the blood is of value in establishing the diagnosis. Soluble antigen is usually found in the blood of patients suffering from severe viraemia and with the methods used has been demonstrated only in patients who are to die of their disease. Haemorrhagic smallpox represents a generalized virus infection of unusual severity in patients who show little resistance to their infection. The cause of this unusual susceptibility is unknown but there is little evidence that specific allergy to the virus is a feature of this form of the disease.This investigation was supported in part by Public Health Service Grant AI–1632–16 VR from the National Institute of Allergy and Infectious Diseases, by the World Health Organization and by the Marcus T. Reynolds III Fund.

scholarly journals A booster dose of an inactivated vaccine increases neutralizing antibodies and T cell responses against SARS-CoV-2

2021 ◽  
Author(s):  
Barbara M Schultz ◽  
Felipe Melo-Gonzalez ◽  
Luisa F Duarte ◽  
Nicolas MS Galvez ◽  
Gaspar A Pacheco ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Cellular Response ◽  
Booster Dose ◽  
Vaccination Schedule ◽  
World Health ◽  
Inactivated Vaccine ◽  
Protective Capacity ◽  
Cell Responses ◽  
Health Organization ◽  
Chilean Population

Numerous vaccines have been generated to decrease the morbidity and mortality of COVID-19. CoronaVac® is an inactivated SARS-CoV-2 vaccine approved by the World Health Organization (WHO) to prevent COVID-19 that has safety and immunogenicity profiles described in different clinical trials. We previously reported an increase in levels of neutralizing antibodies two- and four-weeks after administering two doses of CoronaVac® in a two-week interval (0-14 day) vaccination schedule, as compared to pre-immune sera in adults in the Chilean population that are participating in phase 3 clinical trial. Here we report the levels of antibodies directed against the Receptor Binding Domain of the SARS-CoV-2 spike protein comparing their neutralizing capacities and the cellular response at five months after the second dose and four weeks after a booster (third) dose in volunteers immunized with two doses of CoronaVac®in a four-week interval (0-28 day) vaccination schedule. We observed a decrease in the levels of anti-SARS-CoV-2 antibodies with neutralizing capacities five months after the second dose (GMU 39.0 95% confidence interval (CI)(32.4-47.0), which increased up to 12 times at four weeks after the booster dose (GMU 499.4, 95% CI=370.6-673.0). Equivalent results were observed in adults aged 18-59 years old and individuals ≥60 years old. In the case of cellular response, we observed that activation of specific CD4+ T cells increases in time and reaches its maximum at four weeks after the booster dose in both groups. Our results support the notion that a booster dose of the SARS-CoV-2 inactivated vaccine increases the levels of neutralizing antibodies and the specific cellular response in adults of both groups, which is likely to boost the protective capacity of these vaccines against COVID-19.

scholarly journals Antibody titers measured by commercial assays are correlated with neutralizing antibody titers calibrated by international standards

2021 ◽  
Author(s):  
Yu-An Kung ◽  
Chung-Guei Huang ◽  
Sheng-Yu Huang ◽  
Kuan-Ting Liu ◽  
Peng-Nien Huang ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Geometric Mean ◽  
Neutralizing Antibody ◽  
Diagnostic Techniques ◽  
International Standards ◽  
World Health ◽  
Serum Samples ◽  
Antibody Titers ◽  
Health Organization

The World Health Organization (WHO) has highlighted the importance of an international standard (IS) for SARS-CoV-2 neutralizing antibody titer detection, with the aim of calibrating different diagnostic techniques. In this study, IS was applied to calibrate neutralizing antibody titers (IU/mL) and binding antibody titers (BAU/mL) in response to SARS-CoV-2 vaccines. Serum samples were collected from participants receiving the Moderna (n = 20) and Pfizer (n = 20) vaccines at three time points: pre-vaccination, after one dose, and after two doses. We obtained geometric mean titers of 1404.16 and 928.75 IU/mL for neutralizing antibodies after two doses of the Moderna and Pfizer vaccines, respectively. These values provide an important baseline for vaccine development and the implementation of non-inferiority trials. We also compared three commercially available kits from Roche, Abbott, and MeDiPro for the detection of COVID-19 antibodies based on binding affinity to S1 and/or RBD. Our results demonstrated that antibody titers measured by commercial assays are highly correlated with neutralizing antibody titers calibrated by IS.

scholarly journals Impaired memory B-cell recall responses in the elderly following recurrent influenza vaccination

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0254421
Author(s):  
Rodrigo B. Abreu ◽  
Greg A. Kirchenbaum ◽  
Giuseppe A. Sautto ◽  
Emily F. Clutter ◽  
Ted M. Ross
Keyword(s):  
Influenza Virus ◽  
High Risk ◽  
Antibody Response ◽  
B Cell ◽  
Influenza A ◽  
The Elderly ◽  
World Health ◽  
Memory B Cell ◽  
Virus Vaccination ◽  
Health Organization

Influenza is a highly contagious viral respiratory disease that affects million of people worldwide each year. Annual vaccination is recommended by the World Health Organization with the goal of reducing influenza severity and limiting transmission through elicitation of antibodies targeting the hemagglutinin (HA) glycoprotein. The antibody response elicited by current seasonal influenza virus vaccines is predominantly strain-specific, but pre-existing influenza virus immunity can greatly impact the serological antibody response to vaccination. However, it remains unclear how B cell memory is shaped by recurrent annual vaccination over the course of multiple seasons, especially in high-risk elderly populations. Here, we systematically profiled the B cell response in young adult (18–34 year old) and elderly (65+ year old) vaccine recipients that received annual split inactivated influenza virus vaccination for 3 consecutive seasons. Specifically, the antibody serological and memory B-cell compartments were profiled for reactivity against current and historical influenza A virus strains. Moreover, multiparametric analysis and antibody landscape profiling revealed a transient increase in strain-specific antibodies in the elderly, but with an impaired recall response of pre-existing memory B-cells, plasmablast (PB) differentiation and long-lasting serological changes. This study thoroughly profiles and compares the immune response to recurrent influenza virus vaccination in young and elderly participants unveiling the pitfalls of current influenza virus vaccines in high-risk populations.

scholarly journals Review of Quality Deficiencies Found in Active Pharmaceutical Ingredient Master Files Submitted to the WHO Prequalification of Medicines Programme

2014 ◽  
Vol 17 (2) ◽  
pp. 169 ◽  
Author(s):  
Isabel Ortega Diego ◽  
Antony Fake ◽  
Matthias Stahl ◽  
Lembit Rägo
Keyword(s):  
Technical Assistance ◽  
Active Pharmaceutical Ingredient ◽  
The United States ◽  
World Health ◽  
European Medicines Agency ◽  
United States Food ◽  
Materials Used ◽  
The Stability ◽  
Health Organization ◽  
Over Time

Purpose. The aim of this work was to determine the number and type of active pharmaceutical ingredient (API) quality deficiencies in API Master Files (APIMFs) as submitted to the World Health Organization (WHO) Prequalification of Medicines Programme (PQP). Methods. We conducted a retrospective review of API quality deficiencies identified following the assessment of new APIMFs for non-sterile APIs during a 6-year period from 1 January 2007 to 31 December 2012. All deficiencies were collected, classified and quantified according to the Common Technical Document (CTD) sections and subsections and as groups of commonly raised questions. Results. There were 5446 deficiencies collected from 159 APIMF deficiency letters by CTD section, by selected CTD subsections and by selected CTD subsections and year. More than 50% of the total number of deficiencies related to the manufacturing sections of the CTD, followed by deficiencies concerning the impurities, the API specification and the stability sections of the CTD.  A pattern of API deficiencies across the different CTD subsections and over time was identified. Conclusions. The most frequent critical deficiencies were related to how the specific manufacturing process and the key materials used, in particular the API starting material, impact the API impurities content. The number and pattern of APIMF deficiencies did not change over time. The results are compared to the findings in similar studies as reported by the United States Food and Drug Administration (USFDA), the European Directorate for the Quality of Medicines (EDQM) and the European Medicines Agency (EMA) and similarities and differences are discussed. Our findings highlight the need for greater guidance and technical assistance for API manufacturers submitting APIMFs to the PQP. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Neutralization of SARS-CoV-2 Omicron variant by sera from BNT162b2 or Coronavac vaccine recipients

2021 ◽  
Author(s):  
Lu Lu ◽  
Bobo Mok ◽  
Linlei Chen ◽  
Jacky Chan ◽  
Owen Tsang ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Geometric Mean ◽  
Neutralizing Antibody ◽  
World Health ◽  
Whole Genome Sequence ◽  
Live Virus ◽  
Significant Difference ◽  
Antibody Titers ◽  
Ancestral Virus ◽  
Health Organization

Background The SARS-CoV-2 Omicron variant, designated as a Variant of Concern(VOC) by the World Health Organization, carries numerous spike protein mutations which have been found to evade neutralizing antibodies elicited by COVID-19 vaccines. The susceptibility of Omicron variant by vaccine-induced neutralizing antibodies are urgently needed for risk assessment. Methods Omicron variant strains HKU691 and HKU344-R346K were isolated from patients using TMPRSS2-overexpressing VeroE6 cells. Whole genome sequence was determined using nanopore sequencing. Neutralization susceptibility of ancestral lineage A virus and the Omicron, Delta and Beta variants to sera from 25 BNT162b2 and 25 Coronavac vaccine recipients was determined using a live virus microneutralization assay. Results The Omicron variant strain HKU344-R346K has an additional spike R346K mutation, which is present in 8.5% of strains in GISAID database. Only 20% and 24% of BNT162b2 recipients had detectable neutralizing antibody against the Omicron variant HKU691 and HKU344-R346K, respectively, while none of the Coronavac recipients had detectable neutralizing antibody titer against either Omicron isolates. For BNT162b2 recipients, the geometric mean neutralization antibody titers(GMT) of the Omicron variant isolates(5.43 and 6.42) were 35.7-39.9-fold lower than that of the ancestral virus(229.4), and the GMT of both omicron isolates were significantly lower than those of the beta and delta variants. There was no significant difference in the GMT between HKU691 and HKU344-R346K. Conclusions Omicron variant escapes neutralizing antibodies elicited by BNT162b2 or CoronaVac. The additional R346K mutation did not affect the neutralization susceptibility. Our data suggest that the Omicron variant may be associated with lower COVID-19 vaccine effectiveness.

scholarly journals Seroprevalence of polio antibodies in adult laboratory staff in South Africa, 2009 to 2013

2016 ◽  
Vol 31 (2) ◽  
pp. 57-60
Author(s):  
Shelina Moonsamy ◽  
Melinda Suchard
Keyword(s):  
South African ◽  
Communicable Diseases ◽  
World Health ◽  
Laboratory Staff ◽  
Population Immunity ◽  
Antibody Titres ◽  
Global Eradication ◽  
Health Organization ◽  
Type 3 ◽  
Health Programme

The global eradication of polio has been a World Health Organization goal since May 1988 with the current target for global eradication set at 2018. A keystone of the eradication initiative is achieving and maintaining high immunisation coverage, producing high population immunity. Assessing infant vaccination coverage does not give a reliable indication of adult immunity levels as antibody titres decline with age. A requirement of the occupational health programme at the National Institute for Communicable Diseases is to test newly appointed personnel for immunity to polio. During the period 2009 to 2013, 352 sera were collected and tested by means of antibody neutralisation assays to determine immunity to all three polio serotypes. The objective of this study was to assess immunity to polio in personnel employed at the National Institute for Communicable Diseases as a proxy for the general adult South African population. The seroprevalence to polio serotypes 1, 2 and 3 were 85.5, 90.0 and 74.0%, respectively. Of the 352 samples tested, 2.3% were sero-negative for all three serotypes and 36.0% were sero-negative to at least one of the serotypes. The seroprevalence to polio serotype 3 falls below the target of 80.0%, and could pose a potential risk following importation or development of vaccine derived poliovirus type 3.

scholarly journals Mutations that confer resistance to broadly-neutralizing antibodies define HIV-1 variants of transmitting mothers from that of non-transmitting mothers

2021 ◽  
Author(s):  
Amit Kumar ◽  
Elena E Giorgi ◽  
Joshua J Tu ◽  
David R Martinez ◽  
Joshua Eudailey ◽  
...  
Keyword(s):  
Vertical Transmission ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Maternal Plasma ◽  
Pediatric Hiv ◽  
World Health ◽  
Autologous Plasma ◽  
Maternal Risk ◽  
Health Organization ◽  
Hiv 1

Despite considerable reduction of mother-to-child transmission (MTCT) of HIV through use of maternal and infant antiretroviral therapy (ART), over 150,000 infants continue to become infected with HIV annually, falling far short of the World Health Organization goal of reaching <20,000 annual pediatric HIV cases worldwide by 2020. Prior to the widespread use of ART in the setting of pregnancy, over half of infants born to HIV-infected mothers were protected against HIV acquisition. Yet, the role of maternal immune factors in this protection against vertical transmission is still unclear, hampering the development of synergistic strategies to further reduce MTCT. It has been established that infant transmitted/founder (T/F) viruses are often resistant to maternal plasma, yet it is unknown if the neutralization resistance profile of circulating viruses predicts the maternal risk of transmission to her infant. In this study, we amplified HIV-1 envelope genes (env) by single genome amplification and produced representative Env variants from plasma of 19 non-transmitting mothers from the U.S. Women Infant Transmission Study (WITS), enrolled in the pre-ART era. Maternal HIV Env variants from non-transmitting mothers had similar sensitivity to autologous plasma as observed for non-transmitting variants from transmitting mothers. In contrast, infant variants were on average 30% less sensitive to paired plasma neutralization compared to non-transmitted maternal variants from both transmitting and non-transmitting mothers (p=0.015). Importantly, a signature sequence analysis revealed that motifs enriched in env sequences from transmitting mothers were associated with broadly neutralizing antibody (bnAb) resistance. Altogether, our findings suggest that circulating maternal virus resistance to bnAb-mediated neutralization, but not autologous plasma neutralization, near the time of delivery, predicts increased MTCT risk. These results caution that enhancement of maternal plasma neutralization through passive or active vaccination during pregnancy could drive the evolution of variants fit for vertical transmission.

scholarly journals Coronavirus Disease in South Korea: Antibody Testing from the Perspective of Effective Quarantine Measures

2021 ◽  
Author(s):  
Insuk Sim ◽  
Yun-Jung Kang
Keyword(s):  
Neutralizing Antibodies ◽  
Control Measure ◽  
Population Level ◽  
Asymptomatic Infection ◽  
Control Measures ◽  
World Health ◽  
Asian Countries ◽  
Antibody Testing ◽  
The Public ◽  
Health Organization

The coronavirus disease (COVID-19) pandemic, which began in December 2019, spread rapidly across Asian countries in January and February 2020 and again after March 2020. COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by fever, cough, and dyspnea. On January 31, 2020, the World Health Organization declared the Public Health Emergency of International Concern. Quarantine authorities are constantly working to prevent the spread of COVID-19. One of the control measures is preparing for national antibody testing, as another wave of infection is expected to occur in the fall of 2021. There are three reasons for antibody testing from a prevention perspective. First, it can identify people with asymptomatic infection. Second, it can detect whether neutralizing antibodies are produced in individuals who have already been infected. Third, it can confirm collective immunity at a community or population level. Considering the lack of effective antiviral drugs or vaccines, the strategy of implementing an effective antibody testing program is an important control measure to minimize the damage caused by the COVID-19 pandemic.

scholarly journals An Overview on Lambda, Epsilon, Kappa, Iota and Zeta Variants of Covid-19 and its Probability to Merge with Delta & Delta Plus, why it is a Concern

2021 ◽  
Vol 12 (5) ◽  
pp. 6895-6914
Keyword(s):  
World Health Organization ◽  
Neutralizing Antibodies ◽  
Spike Protein ◽  
World Health ◽  
South American ◽  
Infected Person ◽  
High Prevalence ◽  
The World ◽  
Health Organization

COVID-19 is caused by the virus SARS-CoV-2 that belongs to the Corona groups. The subgroups of the coronavirus families are α, β, γ, and δ coronavirus. On June 15, 2021, the string λ of SARS-CoV-2 was evaluated as a variant of interest via the World Health Organization. This string has a high prevalence in some parts of South American countries, but it occurred only occasionally in Brazil. This study confirms that mutations in the λ -spike protein can be destroyed the neutralizing antibodies and increase infectivity. Coronaviruses such as SARS-CoV-2 have an evolutionary superpower called “recombination” which permits the mixing of their genomes into novel combinations. Unlike regular mutation, which precedes slowly one change at a time, recombination can produce whole changes in a coronavirus genome. Although right now, δ-variant is a concern, a mixing of λ with other variants such as δ-variant is much more of a concern compared to alone variants. There is another item: the recombination can arise within the sample after it was taken from the infected person, not while it was inside their body.

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