scholarly journals Immunization with Modified Vaccinia Virus Ankara-Based Recombinant Vaccine against Severe Acute Respiratory Syndrome Is Associated with Enhanced Hepatitis in Ferrets

2004 ◽  
Vol 78 (22) ◽  
pp. 12672-12676 ◽  
Author(s):  
Hana Weingartl ◽  
Markus Czub ◽  
Stefanie Czub ◽  
James Neufeld ◽  
Peter Marszal ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Severe Acute Respiratory Syndrome ◽  
Antibody Response ◽  
Vaccinia Virus ◽  
Inflammatory Responses ◽  
Neutralizing Antibody ◽  
Mustela Putorius ◽  
S Protein ◽  
Modified Vaccinia Virus Ankara ◽  
Human Infectious Disease

ABSTRACT Severe acute respiratory syndrome (SARS) caused by a newly identified coronavirus (SARS-CoV) is a serious emerging human infectious disease. In this report, we immunized ferrets (Mustela putorius furo) with recombinant modified vaccinia virus Ankara (rMVA) expressing the SARS-CoV spike (S) protein. Immunized ferrets developed a more rapid and vigorous neutralizing antibody response than control animals after challenge with SARS-CoV; however, they also exhibited strong inflammatory responses in liver tissue. Inflammation in control animals exposed to SARS-CoV was relatively mild. Thus, our data suggest that vaccination with rMVA expressing SARS-CoV S protein is associated with enhanced hepatitis.

scholarly journals Recombinant Modified Vaccinia Virus Ankara Expressing the Surface gp120 of Simian Immunodeficiency Virus (SIV) Primes for a Rapid Neutralizing Antibody Response to SIV Infection in Macaques

2000 ◽  
Vol 74 (6) ◽  
pp. 2960-2965 ◽  
Author(s):  
Ilnour Ourmanov ◽  
Miroslawa Bilska ◽  
Vanessa M. Hirsch ◽  
David C. Montefiori
Keyword(s):  
Antibody Response ◽  
Vaccinia Virus ◽  
Simian Immunodeficiency Virus ◽  
Neutralizing Antibodies ◽  
Rhesus Macaques ◽  
Neutralizing Antibody ◽  
Anamnestic Response ◽  
Modified Vaccinia Virus Ankara ◽  
Immunodeficiency Virus ◽  
Before And After

ABSTRACT Neutralizing antibodies were assessed before and after intravenous challenge with pathogenic SIVsmE660 in rhesus macaques that had been immunized with recombinant modified vaccinia virus Ankara expressing one or more simian immunodeficiency virus gene products (MVA-SIV). Animals received either MVA-gag-pol, MVA-env, MVA-gag-pol-env, or nonrecombinant MVA. Although no animals were completely protected from infection with SIV, animals immunized with recombinant MVA-SIV vaccines had lower virus loads and prolonged survival relative to control animals that received nonrecombinant MVA (I. Ourmanov et al., J. Virol. 74:2740–2751, 2000). Titers of neutralizing antibodies measured with the vaccine strain SIVsmH-4 were low in the MVA-env and MVA-gag-pol-env groups of animals and were undetectable in the MVA-gag-pol and nonrecombinant MVA groups of animals on the day of challenge (4 weeks after final immunization). Titers of SIVsmH-4-neutralizing antibodies remained unchanged 1 week later but increased approximately 100-fold 2 weeks postchallenge in the MVA-env and MVA-gag-pol-env groups while the titers remained low or undetectable in the MVA-gag-pol and nonrecombinant MVA groups. This anamnestic neutralizing antibody response was also detected with T-cell-line-adapted stocks of SIVmac251 and SIV/DeltaB670 but not with SIVmac239, as this latter virus resisted neutralization. Most animals in each group had high titers of SIVsmH-4-neutralizing antibodies 8 weeks postchallenge. Titers of neutralizing antibodies were low or undetectable until about 12 weeks of infection in all groups of animals and showed little or no evidence of an anamnestic response when measured with SIVsmE660. The results indicate that recombinant MVA is a promising vector to use to prime for an anamnestic neutralizing antibody response following infection with primate lentiviruses that cause AIDS. However, the Env component of the present vaccine needs improvement in order to target a broad spectrum of viral variants, including those that resemble primary isolates.

scholarly journals A single immunization with a rhabdovirus-based vector expressing severe acute respiratory syndrome coronavirus (SARS-CoV) S protein results in the production of high levels of SARS-CoV-neutralizing antibodies

2005 ◽  
Vol 86 (5) ◽  
pp. 1435-1440 ◽  
Author(s):  
Milosz Faber ◽  
Elaine W. Lamirande ◽  
Anjeanette Roberts ◽  
Amy B. Rice ◽  
Hilary Koprowski ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Protein S ◽  
S Protein ◽  
Cellular Immune Responses ◽  
Glycoprotein G ◽  
Cellular Immune ◽  
Animal Reservoirs ◽  
S Genes

Foreign viral proteins expressed by rabies virus (RV) have been shown to induce potent humoral and cellular immune responses in immunized animals. In addition, highly attenuated and, therefore, very safe RV-based vectors have been constructed. Here, an RV-based vaccine vehicle was utilized as a novel vaccine against severe acute respiratory syndrome coronavirus (SARS-CoV). For this approach, the SARS-CoV nucleocapsid protein (N) or envelope spike protein (S) genes were cloned between the RV glycoprotein G and polymerase L genes. Recombinant vectors expressing SARS-CoV N or S protein were recovered and their immunogenicity was studied in mice. A single inoculation with the RV-based vaccine expressing SARS-CoV S protein induced a strong SARS-CoV-neutralizing antibody response. The ability of the RV-SARS-CoV S vector to confer immunity after a single inoculation makes this live vaccine a promising candidate for eradication of SARS-CoV in animal reservoirs, thereby reducing the risk of transmitting the infection to humans.

scholarly journals The antibody response of rabbits to inactivated vaccinia virus

1965 ◽  
Vol 63 (4) ◽  
pp. 525-535 ◽  
Author(s):  
T. A. McNeill
Keyword(s):  
Antibody Response ◽  
Vaccinia Virus ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Single Factor

Inactivated vaccinia virus vaccines were prepared from purified virus inactivated by either formalin, hydroxylamine or heat. The immunogenicity of these vaccines was assessed in rabbits by measurement of virus neutralizing antibody following each of two inoculations. It was concluded that inactivated vaccinia virus stimulates the production of neutralizing antibody and that the most important single factor in this immunogenicity is the concentration of virus in the vaccine. Vaccines prepared from virus suspensions containing 107 to 108 pfu/ml. before inactivation give variable antibody responses.

scholarly journals Response and Duration of Serum Anti-SARS-CoV-2 Antibodies After Inactivated Vaccination Within 160 Days

2021 ◽  
Vol 12 ◽  
Author(s):  
Qiu-Yan Xu ◽  
Jian-Hang Xue ◽  
Yao Xiao ◽  
Zhi-Juan Jia ◽  
Meng-Juan Wu ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Severe Acute Respiratory Syndrome ◽  
Antibody Response ◽  
Predictive Value ◽  
Neutralizing Antibodies ◽  
Logistic Regression Model ◽  
Neutralizing Antibody ◽  
Effective Protection ◽  
Seropositivity Rate ◽  
Antibody Persistence

BackgroundA vaccine against coronavirus disease 2019 (COVID-19) with highly effective protection is urgently needed. The anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody response and duration after vaccination are crucial predictive indicators.ObjectivesTo evaluate the response and duration for 5 subsets of anti-SARS-CoV-2 antibodies after vaccination and their predictive value for protection.MethodsWe determined the response and duration for 5 subsets of anti-SARS-CoV-2 antibodies (neutralizing antibody, anti-RBD total antibody, anti-Spike IgG, anti-Spike IgM, and anti-Spike IgA) in 61 volunteers within 160 days after the CoronaVac vaccine. A logistic regression model was used to determine the predictors of the persistence of neutralizing antibody persistence.ResultsThe seropositivity rates of neutralizing antibody, anti-RBD total antibody, anti-Spike IgG, anti-Spike IgM, and anti-Spike IgA were only 4.92%, 27.87%, 21.31%, 3.28% and 0.00%, respectively, at the end of the first dose (28 days). After the second dose, the seropositivity rates reached peaks of 95.08%, 100.00%, 100.00%, 59.02% and 31.15% in two weeks (42 days). Their decay was obvious and the seropositivity rate remained at 19.67%, 54.10%, 50.82%, 3.28% and 0.00% on day 160, respectively. The level of neutralizing antibody reached a peak of 149.40 (101.00–244.60) IU/mL two weeks after the second dose (42 days) and dropped to 14.23 (7.62–30.73) IU/mL at 160 days, with a half-life of 35.61(95% CI, 32.68 to 39.12) days. Younger participants (≤31 years) had 6.179 times more persistent neutralizing antibodies than older participants (>31 years) (P<0.05). Participants with anti-Spike IgA seropositivity had 4.314 times greater persistence of neutralizing antibodies than participants without anti-Spike IgA seroconversion (P<0.05).ConclusionsAntibody response for the CoronaVac vaccine was intense and comprehensive with 95.08% neutralizing seropositivity rate, while decay was also obvious after 160 days. Therefore, booster doses should be considered in the vaccine strategies.

scholarly journals Evaluation of Human Monoclonal Antibody 80R for Immunoprophylaxis of Severe Acute Respiratory Syndrome by an Animal Study, Epitope Mapping, and Analysis of Spike Variants

2005 ◽  
Vol 79 (10) ◽  
pp. 5900-5906 ◽  
Author(s):  
Jianhua Sui ◽  
Wenhui Li ◽  
Anjeanette Roberts ◽  
Leslie J. Matthews ◽  
Akikazu Murakami ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Amino Acid ◽  
Severe Acute Respiratory Syndrome ◽  
Human Monoclonal Antibody ◽  
Neutralizing Antibody ◽  
Index Patient ◽  
Binding Domain ◽  
S Protein

ABSTRACT In this report, the antiviral activity of 80R immunoglobulin G1 (IgG1), a human monoclonal antibody against severe acute respiratory syndrome coronavirus (SARS-CoV) spike (S) protein that acts as a viral entry inhibitor in vitro, was investigated in vivo in a mouse model. When 80R IgG1 was given prophylactically to mice at doses therapeutically achievable in humans, viral replication was reduced by more than 4 orders of magnitude to below assay limits. The essential core region of S protein required for 80R binding was identified as a conformationally sensitive fragment (residues 324 to 503) that overlaps the receptor ACE2-binding domain. Amino acids critical for 80R binding were identified. In addition, the effects of various 80R-binding domain amino acid substitutions which occur in SARS-like-CoV from civet cats, and which evolved during the 2002/2003 outbreak and in a 2003/2004 Guangdong index patient, were analyzed. The results demonstrated that the vast majority of SARS-CoVs are sensitive to 80R. We propose that by establishing the susceptibility and resistance profiles of newly emerging SARS-CoVs through early S1 genotyping of the core 180-amino-acid neutralizing epitope of 80R, an effective immunoprophylaxis strategy with 80R should be possible in an outbreak setting. Our study also cautions that for any prophylaxis strategy based on neutralizing antibody responses, whether by passive or active immunization, a genotyping monitor will be necessary for effective use.

scholarly journals Robust neutralizing antibodies to SARS-CoV-2 infection persist for months

Science ◽  
2020 ◽  
Vol 370 (6521) ◽  
pp. 1227-1230 ◽  
Author(s):  
Ania Wajnberg ◽  
Fatima Amanat ◽  
Adolfo Firpo ◽  
Deena R. Altman ◽  
Mark J. Bailey ◽  
...  
Keyword(s):  
New York ◽  
New York City ◽  
Severe Acute Respiratory Syndrome ◽  
Antibody Response ◽  
York City ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Spike Protein ◽  
Global Pandemic

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic with millions infected and more than 1 million fatalities. Questions regarding the robustness, functionality, and longevity of the antibody response to the virus remain unanswered. Here, on the basis of a dataset of 30,082 individuals screened at Mount Sinai Health System in New York City, we report that the vast majority of infected individuals with mild-to-moderate COVID-19 experience robust immunoglobulin G antibody responses against the viral spike protein. We also show that titers are relatively stable for at least a period of about 5 months and that anti-spike binding titers significantly correlate with neutralization of authentic SARS-CoV-2. Our data suggest that more than 90% of seroconverters make detectable neutralizing antibody responses. These titers remain relatively stable for several months after infection.

scholarly journals Identifying Epitopes Responsible for Neutralizing Antibody and DC-SIGN Binding on the Spike Glycoprotein of the Severe Acute Respiratory Syndrome Coronavirus

2006 ◽  
Vol 80 (21) ◽  
pp. 10315-10324 ◽  
Author(s):  
Yi-Ping Shih ◽  
Chia-Yen Chen ◽  
Shih-Jen Liu ◽  
Kuan-Hsuan Chen ◽  
Yuan-Ming Lee ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Binding Capacity ◽  
Neutralizing Antibody ◽  
Observation Data ◽  
S Protein ◽  
Angiotensin Converting Enzyme 2 ◽  
Capture Assay ◽  
Immature Dendritic Cells ◽  
Glycosylation Sites ◽  
Peptide Display

ABSTRACT The severe acute respiratory syndrome-associated coronavirus (SARS-CoV) uses dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN) to facilitate cell entry via cellular receptor-angiotensin-converting enzyme 2. For this project, we used recombinant baculoviruses expressing different lengths of SARS-CoV spike (S) protein in a capture assay to deduce the minimal DC-SIGN binding region. Our results identified the region location between amino acid (aa) residues 324 to 386 of the S protein. We then generated nine monoclonal antibodies (MAbs) against the S protein to map the DC-SIGN-binding domain using capture assays with pseudotyped viruses and observed that MAb SIa5 significantly blocked S protein-DC-SIGN interaction. An enhancement assay using the HKU39849 SARS-CoV strain and human immature dendritic cells confirmed our observation. Data from a pepscan analysis and M13 phage peptide display library system mapped the reactive MAb SIa5 epitope to aa residues 363 to 368 of the S protein. Results from a capture assay testing three pseudotyped viruses with mutated N-linked glycosylation sites of the S protein indicate that only two pseudotyped viruses (N330Q and N357Q, both of which lost glycosylation sites near the SIa5 epitope) had diminished DC-SIGN-binding capacity. We also noted that MAb SIb4 exerted a neutralizing effect against HKU39849; its reactive epitope was mapped to aa residues 435 to 439 of the S protein. We offer the data to facilitate the development of therapeutic agents and preventive vaccines against SARS-CoV infection.

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