scholarly journals Insights into neutralizing antibody responses in individuals exposed to SARS-CoV-2 in Chile

2021 ◽  
Vol 7 (7) ◽  
pp. eabe6855 ◽  
Author(s):  
Carolina Beltrán-Pavez ◽  
Sebastián Riquelme-Barrios ◽  
Aarón Oyarzún-Arrau ◽  
Aracelly Gaete-Argel ◽  
Roxana González-Stegmaier ◽  
...  
Keyword(s):  
General Population ◽  
Local Level ◽  
Neutralizing Antibody ◽  
Host Immunity ◽  
Antibody Responses ◽  
Wild Type ◽  
Neutralization Activity ◽  
Future Studies

Chile has one of the worst numbers worldwide in terms of SARS-CoV-2 positive cases and COVID-19–related deaths per million inhabitants; thus, characterization of neutralizing antibody (NAb) responses in the general population is critical to understanding of immunity at the local level. Given our inability to perform massive classical neutralization assays due to the scarce availability of BSL-3 facilities in the country, we developed and fully characterized an HIV-based SARS-CoV-2 pseudotype, which was used in a 96-well plate format to investigate NAb responses in samples from individuals exposed to SARS-CoV-2 or treated with convalescent plasma. We also identified samples with decreased or enhanced neutralization activity against the D614G spike variant compared with the wild type, indicating the relevance of this variant in host immunity. The data presented here represent the first insights into NAb responses in individuals from Chile, serving as a guide for future studies in the country.

scholarly journals Immunogenicity of HIV-1-Based Virus-Like Particles with Increased Incorporation and Stability of Membrane-Bound Env

Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 239
Author(s):  
Christopher A. Gonelli ◽  
Hannah A. D. King ◽  
Charlene Mackenzie ◽  
Secondo Sonza ◽  
Rob J. Center ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Neutralization Activity ◽  
Virus Like Particles ◽  
Antibody Isotypes ◽  
Immunodeficiency Virus ◽  
Proline Substitution ◽  
Membrane Bound ◽  
Antibody Epitopes ◽  
Hiv 1

An optimal prophylactic vaccine to prevent human immunodeficiency virus (HIV-1) transmission should elicit protective antibody responses against the HIV-1 envelope glycoprotein (Env). Replication-incompetent HIV-1 virus-like particles (VLPs) offer the opportunity to present virion-associated Env with a native-like structure during vaccination that closely resembles that encountered on infectious virus. Here, we optimized the incorporation of Env into previously designed mature-form VLPs (mVLPs) and assessed their immunogenicity in mice. The incorporation of Env into mVLPs was increased by replacing the Env transmembrane and cytoplasmic tail domains with those of influenza haemagglutinin (HA-TMCT). Furthermore, Env was stabilized on the VLP surface by introducing an interchain disulfide and proline substitution (SOSIP) mutations typically employed to stabilize soluble Env trimers. The resulting mVLPs efficiently presented neutralizing antibody epitopes while minimizing exposure of non-neutralizing antibody sites. Vaccination of mice with mVLPs elicited a broader range of Env-specific antibody isotypes than Env presented on immature VLPs or extracellular vesicles. The mVLPs bearing HA-TMCT-modified Env consistently induced anti-Env antibody responses that mediated modest neutralization activity. These mVLPs are potentially useful immunogens for eliciting neutralizing antibody responses that target native Env epitopes on infectious HIV-1 virions.

scholarly journals Characterization of broadly neutralizing antibody responses to HIV-1 in a cohort of long term non-progressors

PLoS ONE ◽  
2018 ◽  
Vol 13 (3) ◽  
pp. e0193773 ◽  
Author(s):  
Nuria González ◽  
Krisha McKee ◽  
Rebecca M. Lynch ◽  
Ivelin S. Georgiev ◽  
Laura Jimenez ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Broadly Neutralizing Antibody ◽  
Hiv 1

scholarly journals Glycosylation of Immunodominant Linear Epitopes in the Carboxy-Terminal Region of the Caprine Arthritis-Encephalitis Virus Surface Envelope Enhances Vaccine-Induced Type-Specific and Cross-Reactive Neutralizing Antibody Responses

2004 ◽  
Vol 78 (17) ◽  
pp. 9190-9202 ◽  
Author(s):  
J. D. Trujillo ◽  
N. M. Kumpula-McWhirter ◽  
K. J. Hötzel ◽  
M. Gonzalez ◽  
W. P. Cheevers
Keyword(s):  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Fold Increase ◽  
Antibody Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Wild Type ◽  
Virus Surface ◽  
Antibody Titers ◽  
Linear Epitopes ◽  
Carboxy Terminal

ABSTRACT This study evaluated type-specific and cross-reactive neutralizing antibodies induced by immunization with modified surface glycoproteins (SU) of the 63 isolate of caprine arthritis-encephalitis lentivirus (CAEV-63). Epitope mapping of sera from CAEV-infected goats localized immunodominant linear epitopes in the carboxy terminus of SU. Two modified SU (SU-M and SU-T) and wild-type CAEV-63 SU (SU-W) were produced in vaccinia virus and utilized to evaluate the effects of glycosylation or the deletion of immunodominant linear epitopes on neutralizing antibody responses induced by immunization. SU-M contained two N-linked glycosylation sites inserted into the target epitopes by R539S and E542N mutations. SU-T was truncated at 518A, upstream from the target epitopes, by introduction of termination codons at 519Y and 521Y. Six yearling Saanen goats were immunized subcutaneously with 30 μg of SU-W, SU-M, or SU-T in Quil A adjuvant and boosted at 3, 7, and 16 weeks. SU antibody titers determined by indirect enzyme-linked immunosorbent assay demonstrated anamnestic responses after each boost. Wild-type and modified SU-induced type-specific CAEV-63 neutralizing antibodies and cross-reactive neutralizing antibodies against CAEV-Co, a virus isolate closely related to CAEV-63, and CAEV-1g5, an isolate geographically distinct from CAEV-63, were determined. Immunization with SU-T resulted in altered recognition of SU linear epitopes and a 2.8- to 4.6-fold decrease in neutralizing antibody titers against CAEV-63, CAEV-Co, and CAEV-1g5 compared to titers of SU-W-immunized goats. In contrast, immunization with SU-M resulted in reduced recognition of glycosylated epitopes and a 2.4- to 2.7-fold increase in neutralizing antibody titers compared to titers of SU-W-immunized goats. Thus, the glycosylation of linear immunodominant nonneutralization epitopes, but not epitope deletion, is an effective strategy to enhance neutralizing antibody responses by immunization.

scholarly journals Impaired Vaccine-Induced Antibody Response Against Clade 6B H1N1 Viruses in Individuals Before Viral Emergence

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Kuan-Ying A Huang ◽  
Yhu-Chering Huang ◽  
Cheng-Hsun Chiu ◽  
Kuo-Chien Tsao ◽  
Tzou-Yien Lin
Keyword(s):  
Age Groups ◽  
Antigenic Site ◽  
Neutralizing Antibody ◽  
Influenza Viruses ◽  
Antibody Responses ◽  
Human Antibody ◽  
Antigenic Characterization ◽  
Before And After ◽  
Viral Emergence

Abstract Background Clade 6B H1N1 pdm09 influenza viruses cause substantial morbidity and mortality worldwide. Human antibody profiles elicited upon vaccination against the clade 6B virus are largely unclear before viral emergence. Methods Healthy volunteers, including children aged 3–8 years, adolescents aged 9–17 years, and adults, were enrolled before the clade 6B H1N1 outbreak and received the 2013–2014 inactivated influenza vaccine. We determined antibody responses before and after vaccination. Vaccine-induced plasmablast-derived antibodies were tested against H1N1 pdm09 reference and clade 6B viruses. Results The majority of the subjects generated robust hemagglutination inhibition and neutralizing antibody responses upon vaccination across the different age groups. Nevertheless, a subset of young adults preferentially produced antibodies that failed to neutralize clade 6B viruses that emerged and circulated in 2014–2016. The hemagglutinin K163Q change at the Sa antigenic site, one of the substitutions that define clade 6B viruses, was responsible for resistance to neutralization by both postvaccination sera and vaccine-induced plasmablast-derived antibodies. Conclusions Vaccine-induced antibody immunity is compromised by the antigenic change of H1N1 pdm09 virus in a subset of adults, and this may warrant the incorporation of human serology in the antigenic characterization of virus and vaccine strain selection.

scholarly journals Comparison of Human H3N2 Antibody Responses Elicited by Egg-Based, Cell-Based, and Recombinant Protein–Based Influenza Vaccines During the 2017–2018 Season

2019 ◽  
Vol 71 (6) ◽  
pp. 1447-1453 ◽  
Author(s):  
Sigrid Gouma ◽  
Seth J Zost ◽  
Kaela Parkhouse ◽  
Angela Branche ◽  
David J Topham ◽  
...  
Keyword(s):  
Recombinant Protein ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Influenza Vaccines ◽  
Vaccine Antigen ◽  
H3n2 Virus ◽  
High Dose ◽  
Wild Type ◽  
H1n1 Vaccine ◽  
Antibody Titers

Abstract Background The H3N2 component of egg-based 2017–2018 influenza vaccines possessed an adaptive substitution that alters antigenicity. Several influenza vaccines include antigens that are produced through alternative systems, but a systematic comparison of different vaccines used during the 2017–2018 season has not been completed. Methods We compared antibody responses in humans vaccinated with Fluzone (egg-based, n = 23), Fluzone High-Dose (egg-based, n = 16), Flublok (recombinant protein–based, n = 23), or Flucelvax (cell-based, n = 23) during the 2017–2018 season. We completed neutralization assays using an egg-adapted H3N2 virus, a cell-based H3N2 virus, wild-type 3c2.A and 3c2.A2 H3N2 viruses, and the H1N1 vaccine strain. We also performed enzyme-linked immunosorbent assays using a recombinant wild-type 3c2.A hemagglutinin. Antibody responses were compared in adjusted analysis. Results Postvaccination neutralizing antibody titers to 3c2.A and 3c2.A2 were higher in Flublok recipients compared with Flucelvax or Fluzone recipients (P < .01). Postvaccination titers to 3c2.A and 3c2.A2 were similar in Flublok and Fluzone High-Dose recipients, though seroconversion rates trended higher in Flublok recipients. Postvaccination titers in Flucelvax recipients were low to all H3N2 viruses tested, including the cell-based H3N2 strain. Postvaccination neutralizing antibody titers to H1N1 were similar among the different vaccine groups. Conclusions These data suggest that influenza vaccine antigen match and dose are both important for eliciting optimal H3N2 antibody responses in humans. Future studies should be designed to determine if our findings directly impact vaccine effectiveness. Clinical Trials Registration NCT03068949.

scholarly journals Redundancy and Plasticity of Neutralizing Antibody Responses Are Cornerstone Attributes of the Human Immune Response to the Smallpox Vaccine

2008 ◽  
Vol 82 (7) ◽  
pp. 3751-3768 ◽  
Author(s):  
Mohammed Rafii-El-Idrissi Benhnia ◽  
Megan M. McCausland ◽  
Hua-Poo Su ◽  
Kavita Singh ◽  
Julia Hoffmann ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Safety Net ◽  
Antibody Responses ◽  
Smallpox Vaccine ◽  
Human Antibody ◽  
Neutralization Activity ◽  
Antibody Titers ◽  
Human Immune Response ◽  
Human Immune

ABSTRACT The smallpox vaccine is widely considered the gold standard for human vaccines, yet the key antibody targets in humans remain unclear. We endeavored to identify a stereotypic, dominant, mature virion (MV) neutralizing antibody target in humans which could be used as a diagnostic serological marker of protective humoral immunity induced by the smallpox vaccine (vaccinia virus [VACV]). We have instead found that diversity is a defining characteristic of the human antibody response to the smallpox vaccine. We show that H3 is the most immunodominant VACV neutralizing antibody target, as determined by correlation analysis of immunoglobulin G (IgG) specificities to MV neutralizing antibody titers. It was determined that purified human anti-H3 IgG is sufficient for neutralization of VACV; however, depletion or blockade of anti-H3 antibodies revealed no significant reduction in neutralization activity, showing anti-H3 IgG is not required in vaccinated humans (or mice) for neutralization of MV. Comparable results were obtained for human (and mouse) anti-L1 IgG and even for anti-H3 and anti-L1 IgG in combination. In addition to H3 and L1, human antibody responses to D8, A27, D13, and A14 exhibited statistically significant correlations with virus neutralization. Altogether, these data indicate the smallpox vaccine succeeds in generating strong neutralizing antibody responses not by eliciting a stereotypic response to a single key antigen but instead by driving development of neutralizing antibodies to multiple viral proteins, resulting in a “safety net” of highly redundant neutralizing antibody responses, the specificities of which can vary from individual to individual. We propose that this is a fundamental attribute of the smallpox vaccine.

scholarly journals Four SARS-CoV-2 vaccines induce quantitatively different antibody responses against SARS-CoV-2 variants

2021 ◽  
Author(s):  
Marit J. van Gils ◽  
Ayesha H.A. Lavell ◽  
Karlijn van der Straten ◽  
Brent Appelman ◽  
Ilja Bontjer ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Adenovirus Vector ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Wild Type ◽  
Fold Reduction ◽  
Antibody Titers ◽  
Alpha Beta ◽  
Vaccination Campaigns

Emerging and future SARS-CoV-2 variants may jeopardize the effectiveness of vaccination campaigns. We performed a head-to-head comparison of the ability of sera from individuals vaccinated with either one of four vaccines (BNT162b2, mRNA-1273, AZD1222 or Ad26.COV2.S) to recognize and neutralize the four SARS-CoV-2 variants of concern (VOCs; Alpha, Beta, Gamma and Delta). Four weeks after completing the vaccination series, SARS-CoV-2 wild-type neutralizing antibody titers were highest in recipients of BNT162b2 and mRNA-1273 (median titers of 1891 and 3061, respectively), and substantially lower in those vaccinated with the adenovirus vector-based vaccines AZD1222 and Ad26.COV2.S (median titers of 241 and 119, respectively). VOCs neutralization was reduced in all vaccine groups, with the largest (5.8-fold) reduction in neutralization being observed against the Beta variant. Overall, the mRNA vaccines appear superior to adenovirus vector-based vaccines in inducing neutralizing antibodies against VOCs four weeks after the final vaccination.

scholarly journals Vaccination with SARS-CoV-2 variants of concern protects mice from challenge with wild-type virus

PLoS Biology ◽  
2021 ◽  
Vol 19 (12) ◽  
pp. e3001384
Author(s):  
Fatima Amanat ◽  
Shirin Strohmeier ◽  
Philip Meade ◽  
Nicholas Dambrauskas ◽  
Barbara Mühlemann ◽  
...  
Keyword(s):  
Mouse Model ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
Fold Reduction ◽  
Reactive Antibody

Vaccines against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) have been highly efficient in protecting against Coronavirus Disease 2019 (COVID-19). However, the emergence of viral variants that are more transmissible and, in some cases, escape from neutralizing antibody responses has raised concerns. Here, we evaluated recombinant protein spike antigens derived from wild-type SARS-CoV-2 and from variants B.1.1.7, B.1.351, and P.1 for their immunogenicity and protective effect in vivo against challenge with wild-type SARS-CoV-2 in the mouse model. All proteins induced high neutralizing antibodies against the respective viruses but also induced high cross-neutralizing antibody responses. The decline in neutralizing titers between variants was moderate, with B.1.1.7-vaccinated animals having a maximum fold reduction of 4.8 against B.1.351 virus. P.1 induced the most cross-reactive antibody responses but was also the least immunogenic in terms of homologous neutralization titers. However, all antigens protected from challenge with wild-type SARS-CoV-2 in a mouse model.

scholarly journals Coronavirus antibody titres in sera of healthy adults and experimentally infected volunteers

1972 ◽  
Vol 70 (2) ◽  
pp. 235-244 ◽  
Author(s):  
A. F. Bradburne ◽  
B. A. Somerset
Keyword(s):  
General Population ◽  
Virus Strain ◽  
High Frequency ◽  
Haemagglutination Inhibition ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Normal Adult ◽  
Apparent Increase ◽  
Antibody Titres ◽  
Heterologous Antibody

SUMMARYSix coronaviruses isolated in the U.S.A. have been inoculated into volunteers and all produced colds. Between 10 and 20 % of infected volunteers developed heterologous antibody responses after these and other experimental infections with coronaviruses. The haemagglutination-inhibition test with the OC43 virus strain was found to detect antibody rises after infection with a variety of strains.Studies on normal adult sera taken between 1965 and 1970 revealed a high frequency of neutralizing antibody to one strain (229E) and a frequency of HI antibody to strain OC43 which fluctuated from year to year. Complement-fixing antibodies to these two viruses were also found, revealing an apparent increase in the activity of coronaviruses in the general population of the U.K., during the winter of 1968–9.

scholarly journals Characterization of an attenuated SARS-CoV-2 variant with a deletion at the S1/S2 junction of the spike protein

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pui Wang ◽  
Siu-Ying Lau ◽  
Shaofeng Deng ◽  
Pin Chen ◽  
Bobo Wing-Yee Mok ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
T Cell Response ◽  
Spike Protein ◽  
Wild Type Virus ◽  
Wild Type ◽  
Cleavage Motif ◽  
Sterilizing Immunity

AbstractSARS-CoV-2 is of zoonotic origin and contains a PRRA polybasic cleavage motif which is considered critical for efficient infection and transmission in humans. We previously reported on a panel of attenuated SARS-CoV-2 variants with deletions at the S1/S2 junction of the spike protein. Here, we characterize pathogenicity, immunogenicity, and protective ability of a further cell-adapted SARS-CoV-2 variant, Ca-DelMut, in in vitro and in vivo systems. Ca-DelMut replicates more efficiently than wild type or parental virus in Vero E6 cells, but causes no apparent disease in hamsters, despite replicating in respiratory tissues. Unlike wild type virus, Ca-DelMut causes no obvious pathological changes and does not induce elevation of proinflammatory cytokines, but still triggers a strong neutralizing antibody and T cell response in hamsters and mice. Ca-DelMut immunized hamsters challenged with wild type SARS-CoV-2 are fully protected, with little sign of virus replication in the upper or lower respiratory tract, demonstrating sterilizing immunity.

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