SARS-CoV-2 Antibody Response is Associated with Age in Convalescent Outpatients

COVID-19 has had an unprecedented global impact on human health. Understanding the antibody memory responses to infection is one tool needed to effectively control the pandemic. Among 173 outpatients who had virologically confirmed SARS-CoV-2 infection, we evaluated serum antibody concentrations, microneutralization activity, and enumerated SARS-CoV-2 specific B cells in convalescent blood specimens. Serum antibody concentrations were variable, allowing for stratification of the cohort into high and low responders. Serum antibody concentration was associated with microneutralization activity and participant age, with participants under the age of 30 showing the lowest antibody level. Neither participant sex, the timing of blood sampling following the onset of illness, nor the number of SARS-CoV-2 spike protein specific B cells correlated with serum antibody concentration. These data suggest that young adult outpatients did not generate as robust antibody memory, compared with older adults. Further, serum antibody concentration or neutralizing activity trended but did not significantly correlate with the number of SARS-CoV-2 memory B cells. These findings have direct implications for public health policy and current vaccine efforts. Knowledge gained regarding antibody memory following infection will inform the need for vaccination in those previously infected and allow for a better approximation of population-wide protective immunity.

Download Full-text

Variant proteins stimulate more IgM+ GC B-cells revealing a mechanism of cross-reactive recognition by antibody memory

eLife ◽

10.7554/elife.26832 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 7

Author(s):

Bronwen R Burton ◽

Richard K Tennant ◽

John Love ◽

Richard W Titball ◽

David C Wraith ◽

...

Keyword(s):

B Cells ◽

Serum Antibody ◽

Primary Response ◽

Affinity Maturation ◽

Memory B Cells ◽

Virus Envelope ◽

B Cell Memory ◽

The Hierarchical Structure ◽

V Genes ◽

Variant Protein

Vaccines induce memory B-cells that provide high affinity secondary antibody responses to identical antigens. Memory B-cells can also re-instigate affinity maturation, but how this happens against antigenic variants is poorly understood despite its potential impact on driving broadly protective immunity against pathogens such as Influenza and Dengue. We immunised mice sequentially with identical or variant Dengue-virus envelope proteins and analysed antibody and germinal-centre (GC) responses. Variant protein boosts induced GCs with a higher proportion of IgM+ B cells. The most variant protein re-stimulated GCs with the highest proportion of IgM+ cells with the most diverse, least mutated V-genes and with a slower but efficient serum antibody response. Recombinant antibodies from GC B-cells showed a higher affinity for the variant antigen than antibodies from a primary response, confirming a memory origin. This reveals a new process of antibody memory, that IgM memory cells with fewer mutations participate in secondary responses to variant antigens, demonstrating how the hierarchical structure of B-cell memory is used and indicating the potential and limits of cross-reactive antibody based immunity.

Download Full-text

Comparison of the Influenza Virus-Specific Effector and Memory B-Cell Responses to Immunization of Children and Adults with Live Attenuated or Inactivated Influenza Virus Vaccines

Journal of Virology ◽

10.1128/jvi.01957-06 ◽

2006 ◽

Vol 81 (1) ◽

pp. 215-228 ◽

Cited By ~ 143

Author(s):

Sanae Sasaki ◽

Maria C. Jaimes ◽

Tyson H. Holmes ◽

Cornelia L. Dekker ◽

Kutubuddin Mahmood ◽

...

Keyword(s):

Influenza Virus ◽

B Cells ◽

B Cell ◽

Response Rate ◽

Serum Antibody ◽

Memory B Cells ◽

Antibody Responses ◽

Older Children ◽

Cell Responses ◽

Specific Effector

ABSTRACT Cellular immune responses to influenza virus infection and influenza virus vaccination have not been rigorously characterized. We quantified the effector and memory B-cell responses in children and adults after administration of either live attenuated (LAIV) or inactivated (TIV) influenza virus vaccines and compared these to antibody responses. Peripheral blood mononuclear cells were collected at days 0, 7 to 12, and 27 to 42 after immunization of younger children (6 months to 4 years old), older children (5 to 9 years old), and adults. Influenza virus-specific effector immunoglobulin A (IgA) and IgG circulating antibody-secreting cells (ASC) and stimulated memory B cells were detected using an enzyme-linked immunospot assay. Circulating influenza virus-specific IgG and IgA ASC were detected 7 to 12 days after TIV and after LAIV immunization. Seventy-nine percent or more of adults and older children had demonstrable IgG ASC responses, while IgA ASC responses were detected in 29 to 53% of the subjects. The IgG ASC response rate to LAIV immunization in adults was significantly higher than the response rate measured by standard serum antibody assays (26.3% and 15.8% by neutralization and hemagglutination inhibition assays, respectively). IgG ASC and serum antibody responses were relatively low in the younger children compared to older children and adults. TIV, but not LAIV, significantly increased the percentage of circulating influenza virus-specific memory B cells detected at 27 to 42 days after immunization in children and adults. In conclusion, although both influenza vaccines are effective, we found significant differences in the B-cell and antibody responses elicited after LAIV or TIV immunization in adults and older children and between young children and older age groups.

Download Full-text

Long-term persistence of neutralizing memory B cells in SARS-CoV-2

10.21203/rs.3.rs-92527/v1 ◽

2020 ◽

Author(s):

Rowena Bull ◽

Arunasingam Abayasingam ◽

Harikrishnan Balachandran ◽

David Agapiou ◽

Chaturaka Rodrigo ◽

...

Keyword(s):

B Cells ◽

Protective Immunity ◽

Memory B Cells ◽

Cell Repertoire ◽

Neutralising Antibodies ◽

Specific Memory ◽

B Cell Repertoire ◽

Antibody Titres ◽

Selected Subset

Abstract Considerable concerns relating to the duration of protective immunity against SARS-CoV-2 have been raised, with evidence of antibody titres declining rapidly after infection and reports of reinfection. Here we monitored antibody responses against SARS-CoV-2 receptor binding domain (RBD) for up to six months after infection. While antibody titres were maintained, half of the cohort’s neutralising responses had returned to background. However, encouragingly in a selected subset of 13 participants, 12 had detectable RBD-specific memory B cells and these generally increased out to 6 months. Furthermore, we were able to generate monoclonal antibodies with SARS-CoV-2 neutralising capacity from these memory B cells. Overall our study suggests that the loss of neutralising antibodies in plasma may be countered by the maintenance of neutralising capacity in the memory B cell repertoire.

Download Full-text

Antibody-Secreting Cell Responses and Protective Immunity Assessed in Gnotobiotic Pigs Inoculated Orally or Intramuscularly with Inactivated Human Rotavirus

Journal of Virology ◽

10.1128/jvi.72.1.330-338.1998 ◽

1998 ◽

Vol 72 (1) ◽

pp. 330-338 ◽

Cited By ~ 68

Author(s):

Lijuan Yuan ◽

S.-Y. Kang ◽

Lucy A. Ward ◽

Thanh L. To ◽

Linda J. Saif

Keyword(s):

B Cells ◽

Protective Immunity ◽

Memory B Cells ◽

Lymphoid Tissues ◽

Human Rotavirus ◽

Specific Igg ◽

Gnotobiotic Pigs ◽

Group 2 ◽

Intestinal Iga ◽

Group 1

ABSTRACT Newborn gnotobiotic pigs were inoculated twice perorally (p.o.) (group 1) or intramuscularly (i.m.) (group 2) or three times i.m. (group 3) with inactivated Wa strain human rotavirus and challenged with virulent Wa human rotavirus 20 to 24 days later. To assess correlates of protection, antibody-secreting cells (ASC) were enumerated in intestinal and systemic lymphoid tissues from pigs in each group at selected postinoculation days (PID) or postchallenge days. Few virus-specific ASC were detected in any tissues of group 1 pigs prior to challenge. By comparison, groups 2 and 3 had significantly greater numbers of virus-specific immunoglobulin M (IgM) ASC in intestinal and splenic tissues at PID 8 and significantly greater numbers of virus-specific IgG ASC and IgG memory B cells in spleen and blood at challenge. However, as for group 1, few virus-specific IgA ASC or IgA memory B cells were detected in any tissues of group 2 and 3 pigs. Neither p.o. nor i.m. inoculation conferred significant protection against virulent Wa rotavirus challenge (0 to 6% protection rate), and all groups showed significant anamnestic virus-specific IgG and IgA ASC responses. Hence, high numbers of IgG ASC or memory IgG ASC in the systemic lymphoid tissues at the time of challenge did not correlate with protection. Further, our findings suggest that inactivated Wa human rotavirus administered either p.o. or parenterally is significantly less effective in inducing intestinal IgA ASC responses and conferring protective immunity than live Wa human rotavirus inoculated orally, as reported earlier (L. Yuan, L. A. Ward, B. I. Rosen, T. L. To, and L. J. Saif, J. Virol. 70:3075–3083, 1996). Thus, more efficient mucosal delivery systems and rotavirus vaccination strategies are needed to induce intestinal IgA ASC responses, identified previously as a correlate of protective immunity to rotavirus.

Download Full-text

Human Memory B Cells TargetingStaphylococcus aureusExotoxins Are Prevalent with Skin and Soft Tissue Infection

mBio ◽

10.1128/mbio.02125-17 ◽

2018 ◽

Vol 9 (2) ◽

Cited By ~ 6

Author(s):

Adam J. Pelzek ◽

Bo Shopsin ◽

Emily E. Radke ◽

Kayan Tam ◽

Beatrix M. Ueberheide ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Acute Phase ◽

Serum Antibody ◽

Cross Reactivity ◽

Memory B Cells ◽

Host Defenses ◽

Cell Memory ◽

B Cell Memory

ABSTRACTStaphylococcus aureusis a Gram-positive opportunistic pathogen that causes superficial and invasive infections in the hospital and community. High mortality from infection emphasizes the need for improved methods for prevention and treatment. AlthoughS. aureuspossesses an arsenal of virulence factors that contribute to evasion of host defenses, few studies have examined long-term humoral and B-cell responses. Adults with acute-phase skin and soft tissue infections were recruited; blood samples were obtained; andS. aureusisolates, including methicillin-resistant strains, were subjected to genomic sequence analysis. In comparisons of acute-phase sera with convalescent-phase sera, a minority (37.5%) of patients displayed 2-fold or greater increases in antibody titers against three or moreS. aureusantigens, whereas nearly half exhibited no changes, despite the presence of toxin genes in most infecting strains. Moreover, enhanced antibody responses waned over time, which could reflect a defect in B-cell memory or long-lived plasma cells. However, memory B cells reactive with a range ofS. aureusantigens were prevalent at both acute-phase and convalescent-phase time points. While some memory B cells exhibited toxin-specific binding, those cross-reactive with structurally related leucocidin subunits were dominant across patients, suggesting the targeting of conserved epitopes. Memory B-cell reactivity correlated with serum antibody levels for selectedS. aureusexotoxins, suggesting a relationship between the cellular and humoral compartments. Overall, although there was no global defect in the representation of anti-S. aureusmemory B cells, there was evidence of restrictions in the range of epitopes recognized, which may suggest potential therapeutic approaches for augmenting host defenses.IMPORTANCEThe contribution of B-cell memory and long-term antibody responses to host defenses againstS. aureusexotoxins remains poorly understood. Our studies confirmed that infection did not commonly lead to enhanced long-term humoral responses. Whereas circulating memory B cells againstS. aureussecreted exotoxins were prevalent, they were dominated by cross-reactivity with structurally related leucocidin subunits, consistent with recognition of conserved epitopes. These findings also provide the first evidence of a relationship between the reactivity of antistaphylococcal circulating memory B cells and serum antibody levels. In general, infection was not associated with a global defect in B-cell memory forS. aureussecreted factors, and responses were highly dominated by cross-reactivity to structurally related exotoxins, which arguably may alone be suboptimal in providing host defenses. Our studies illuminate aspects of theS. aureus-host relationship that may better inform strategies for the development of an effective protective vaccine.

Download Full-text