SARS-CoV-2 naïve and recovered individuals show qualitatively different antibody responses following mRNA vaccination

mRNA-based vaccines effectively induce protective neutralizing antibody responses against SARS-CoV-2, the etiological agent of COVID-19. The specific compositional patterns of these responses remain largely unknown. We found that SARS-CoV-2-naïve individuals receiving the first dose of an mRNA vaccine developed a SARS-CoV-2-specific antibody response with a subclass profile comparable to that induced by the natural infection, except IgA2, which did not increase. SARS-CoV-2-naïve subjects also mounted a robust virus-specific recall response after receiving the second dose. This response increased all IgG subclasses, but boosted neither IgM nor IgA1 and IgA2 subclasses. In contrast, individuals recovered from COVID-19 mounted peak virus-specific antibody responses upon primary immunization and did not further augment such responses following secondary immunization. Remarkably, compared to SARS-CoV-2-naïve subjects, individuals with pre-existing immunity showed increased levels of all virus-specific antibodies but IgG3 following primary vaccination. By dissecting the heterogeneity of mRNA vaccine-induced humoral responses to SARS-CoV-2, our findings indicate that the induction of optimal immune protection may require the development of personalized vaccination programs.

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Respiratory syncytial virus-specific antibody responses in immunoglobulin A and E isotypes to the F and G proteins and to intact virus after natural infection.

Journal of Clinical Microbiology ◽

10.1128/jcm.27.2.295-299.1989 ◽

1989 ◽

Vol 27 (2) ◽

pp. 295-299 ◽

Cited By ~ 18

Author(s):

R C Welliver ◽

M Sun ◽

S W Hildreth ◽

R Arumugham ◽

P L Ogra

Keyword(s):

Respiratory Syncytial Virus ◽

G Proteins ◽

Specific Antibody ◽

Natural Infection ◽

Immunoglobulin A ◽

Antibody Responses ◽

Intact Virus ◽

Virus Specific Antibody ◽

Syncytial Virus

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IgA dominates the early neutralizing antibody response to SARS-CoV-2

Science Translational Medicine ◽

10.1126/scitranslmed.abd2223 ◽

2020 ◽

pp. eabd2223 ◽

Cited By ~ 4

Author(s):

Delphine Sterlin ◽

Alexis Mathian ◽

Makoto Miyara ◽

Audrey Mohr ◽

François Anna ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Antibody Responses ◽

Immune Memory ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Virus Specific Antibody ◽

Iga Response ◽

Humoral Responses ◽

Antibody Secreting Cells

Humoral immune responses are typically characterized by primary IgM antibody responses followed by secondary antibody responses associated with immune memory and comprised of of IgG, IgA and IgE. Here we measured acute humoral responses to SARS-CoV-2, including the frequency of antibody-secreting cells and the presence of SARS-CoV-2-specific neutralizing antibodies in the serum, saliva and broncho-alveolar fluid of 159 patients with COVID-19. Early SARS-CoV-2-specific humoral responses were dominated by IgA antibodies. Peripheral expansion of IgA plasmablasts with mucosal-homing potential was detected shortly after the onset of symptoms and peaked during the third week of the disease. The virus-specific antibody responses included IgG, IgM and IgA, but IgA contributed to virus neutralization to a greater extent compared with IgG. Specific IgA serum concentrations decreased notably one month after the onset of symptoms, but neutralizing IgA remained detectable in saliva for a longer time (days 49 to 73 post symptoms). These results represent a critical observation given the emerging information as to the types of antibodies associated with optimal protection against re-infection, and whether vaccine regimens should consider targeting a potent but potentially short-lived IgA response.

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IgA dominates the early neutralizing antibody response to SARS-CoV-2

10.1101/2020.06.10.20126532 ◽

2020 ◽

Cited By ~ 28

Author(s):

Delphine Sterlin ◽

Alexis Mathian ◽

Makoto Miyara ◽

Audrey Mohr ◽

François Anna ◽

...

Keyword(s):

Antibody Response ◽

Specific Antibody ◽

Neutralizing Antibodies ◽

Humoral Response ◽

Neutralizing Antibody ◽

Serum Levels ◽

Virus Neutralization ◽

Secondary Memory ◽

Specific Antibody Response ◽

Humoral Responses

AbstractA major dogma in immunology has it that the IgM antibody response precedes secondary memory responses built on the production of IgG, IgA and, occasionaly, IgE. Here, we measured acute humoral responses to SARS-CoV-2, including the frequency of antibody-secreting cells and the presence of specific, neutralizing, antibodies in serum and broncho-alveolar fluid of 145 patients with COVID-19. Surprisingly, early SARS-CoV-2-specific humoral responses were found to be typically dominated by antibodies of the IgA isotype. Peripheral expansion of IgA-plasmablasts with mucosal-homing potential was detected shortly after the onset of symptoms and peaked during the third week of the disease. While the specific antibody response included IgG, IgM and IgA, the latter contributed to a much larger extent to virus neutralization, as compared to IgG. However, specific IgA serum levels notably decrease after one month of evolution. These results represent a challenging observation given the present uncertainty as to which kind of humoral response would optimally protect against re-infection, and whether vaccine regimens should consider boosting a potent, although, at least in blood, fading IgA response.One sentence SummaryWhile early specific antibody response included IgG, IgM and IgA, the latter contributed to a much larger extent to virus neutralization.

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An Adjuvanted A(H5N1) Subvirion Vaccine Elicits Virus-Specific Antibody Response and Improves Protection Against Lethal Influenza Viral Challenge in Mouse Model of Protein Energy Malnutrition

The Journal of Infectious Diseases ◽

10.1093/infdis/jiw585 ◽

2017 ◽

Vol 216 (suppl_4) ◽

pp. S560-S565 ◽

Cited By ~ 1

Author(s):

Enitra N Jones ◽

Samuel Amoah ◽

Weiping Cao ◽

Suryaprakash Sambhara ◽

Shivaprakash Gangappa

Keyword(s):

Mouse Model ◽

Antibody Response ◽

Specific Antibody ◽

Protein Energy Malnutrition ◽

Specific Antibody Response ◽

Viral Challenge ◽

Protein Energy ◽

Virus Specific Antibody

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Specificity and effector functions of non-neutralizing gB-specific monoclonal antibodies isolated from healthy individuals with human cytomegalovirus infection

10.1101/2020.01.14.907204 ◽

2020 ◽

Author(s):

Matthew L. Goodwin ◽

Helen S. Webster ◽

Hsuan-Yuan Wang ◽

Jennifer A. Jenks ◽

Cody S. Nelson ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Human Cytomegalovirus ◽

Effector Cell ◽

Natural Infection ◽

Congenital Infection ◽

Neutralizing Antibody ◽

Antibody Responses ◽

Domain Specificity ◽

Cell Functions ◽

The Impact

AbstractHuman cytomegalovirus (HCMV) is the most common congenital infection, and the leading nongenetic cause of sensorineural hearing loss (SNHL) in newborns globally. A gB subunit vaccine administered with adjuvent MF59 (gB/MF59) is the most efficacious tested to-date, achieving 50% efficacy in preventing infection of HCMV-seronegative mothers. We recently discovered that gB/MF59 vaccination elicited primarily non-neutralizing antibody responses, that HCMV strains acquired by vaccinees more often included strains with gB genotypes that are distinct from the vaccine antigen, and that protection against HCMV acquisition correlated with ability of vaccine-elicited antibodies to bind to membrane associated gB. Thus, we hypothesized that gB-specific non-neutralizing antibody binding breadth and function are dependent on their epitope and genotype specificity as well as their ability to interact with membrane-associated gB. Twenty-four gB-specific monoclonal antibodies (mAbs) isolated from naturally HCMV-infected individuals were mapped for gB domain specificity by binding antibody multiplex assay (BAMA) and for genotype preference binding to membrane-associated gB presented on transfected cells. We defined their non-neutralizing functions including antibody dependent cellular phagocytosis (ADCP) and antibody dependent cellular cytotoxicity (ADCC). The isolated gB-specific non-neutralizing mAbs were primarily specific for Domain II and linear antigenic domain 2 site 2 (AD2). We observed variability in mAb gB genotype binding preference, with increased binding to gB genotypes 2 and 4. Functional studies identified two gB-specific mAbs that facilitate ADCP and have binding specificities of AD2 and Domain II. This investigation provides novel understanding on the impact of gB domain specificity and antigenic variability on gB-specific non-neutralizing antibody responses.ImportanceHCMV is the most common congenital infection worldwide, but development of a successful vaccine remains elusive. gB-specific non-neutralizing mAbs, represent a distinct anti-HCMV Ab subset implicated in the protection against primary infection during numerous phase-II gB/MF59 vaccine trials. By studying non-neutralizing gB-specific mAbs from naturally infected individuals, this study provides novel characterization of binding site specificity, genotypic preference, and effector cell functions mediated by mAbs elicited in natural infection. We found that a panel of twenty-four gB-specific non-neutralizing mAbs bind across multiple regions of the gB protein, traditionally through to be targeted by neutralizing mAbs only, and bind differently to gB depending if the protein is soluble versus embedded in a membrane. This investigation provides novel insight into the gB-specific binding characteristics and effector cell functions mediated by non-neutralizing gB-specific mAbs elicited through natural infection, providing new endpoints for future vaccine development.

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Delayed virus‐specific antibody responses associate with COVID‐19 mortality

Allergy ◽

10.1111/all.14546 ◽

2020 ◽

Author(s):

Feng Wang ◽

Yin Yao ◽

Hongyan Hou ◽

Shiji Wu ◽

Cuilian Guo ◽

...

Keyword(s):

Specific Antibody ◽

Antibody Responses ◽

Virus Specific Antibody

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Interferon activation status underlies higher antibody response to viral antigens in patients with systemic lupus erythematosus receiving no or light treatment

Rheumatology ◽

10.1093/rheumatology/keaa611 ◽

2020 ◽

Author(s):

Albin Björk ◽

Rui Da Silva Rodrigues ◽

Elina Richardsdotter Andersson ◽

Jorge I Ramírez Sepúlveda ◽

Johannes Mofors ◽

...

Keyword(s):

Antibody Response ◽

Specific Antibody ◽

Lupus Erythematosus ◽

Serum Proteins ◽

Light Treatment ◽

Antibody Responses ◽

Type I ◽

Specific Antibody Response ◽

Viral Antigens

Abstract Objectives Infections have been proposed as an environmental risk factor for autoimmune disease. Responses to microbial antigens may be studied in vivo during vaccination. We therefore followed patients with SLE and controls during split-virion influenza vaccination to quantify antibody responses against viral antigens and associated cellular and proteome parameters. Methods Blood samples and clinical data were collected from female patients with SLE with no or HCQ and/or low-dose prednisolone treatment (n = 29) and age- and sex-matched healthy controls (n = 17). Vaccine-specific antibody titres were measured by ELISA and IFN-induced gene expression in monocytes by quantitative PCR. Serum proteins were measured by proximity extension assay and disease-associated symptoms were followed by questionnaires. Results The vaccine-specific antibody response was significantly higher in patients compared with controls and titres of IgG targeting the viral proteins were higher in patients than controls at both 1 and 3 months after immunization. Clinical disease symptoms and autoantibody titres remained unchanged throughout the study. Notably, a positive pre-vaccination mRNA-based IFN score was associated with a significantly higher vaccine-specific antibody response and with a broader profile of autoantibody specificities. Screening of serum protein biomarkers revealed higher levels of IFN-regulated proteins in patients compared with controls and that levels of such proteins correlated with the vaccine-specific IgG response, with C-C motif chemokine ligand 3 exhibiting the strongest association. Conclusion Augmented antibody responses to viral antigens develop in patients with SLE on no or light treatment and associate with markers of type I IFN system activation at the RNA and protein levels.

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Nature and Specificity of the Required Protective Immune Response That Develops Postchallenge in Mice Vaccinated with the 19-Kilodalton Fragment of Plasmodium yoelii Merozoite Surface Protein 1

Infection and Immunity ◽

10.1128/iai.70.11.6013-6020.2002 ◽

2002 ◽

Vol 70 (11) ◽

pp. 6013-6020 ◽

Cited By ~ 11

Author(s):

Jiraprapa Wipasa ◽

Huji Xu ◽

Morris Makobongo ◽

Michelle Gatton ◽

Anthony Stowers ◽

...

Keyword(s):

Immune Response ◽

Antibody Response ◽

Specific Antibody ◽

Natural Infection ◽

Surface Protein ◽

Merozoite Surface Protein ◽

Plasmodium Yoelii ◽

Specific Antibody Response ◽

Specific Antibodies ◽

Merozoite Surface Protein 1

ABSTRACT Immunity induced by the 19-kDa fragment of Plasmodium yoelii merozoite surface protein 1 (MSP119) is dependent on high titers of specific antibodies present at the time of challenge and a continuing active immune response postinfection. However, the specificity of the active immune response postinfection has not been defined. In particular, it is not known whether anti-MSP119 antibodies that arise following infection alone are sufficient for protection. We developed systems to investigate whether an MSP119-specific antibody response alone both prechallenge and postchallenge is sufficient for protection. We were able to exclude antibodies with other specificities, as well as any contribution of MSP119-specific CD4+ T cells acting independent of antibody, and we concluded that an immune response focused solely on MSP119-specific antibodies is sufficient for protection. The data imply that the ability of natural infection to boost an MSP119-specific antibody response should greatly improve vaccine efficacy.

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