scholarly journals Diverse Humoral Immune Responses in Younger and Older Adult COVID-19 Patients

Author(s):  
Jennifer M. Sasson ◽  
Joseph J. Campo ◽  
Rebecca M. Carpenter ◽  
Mary K. Young ◽  
Arlo Z. Randall ◽  
...  

AbstractWe sought to discover links between antibody responses to SARS-CoV-2 and patient clinical variables, cytokine profiles and antibodies to endemic coronaviruses. Serum from patients of varying ages and clinical severity were collected and used to probe a novel multi-coronavirus protein microarray containing SARS-CoV-2 proteins and overlapping protein fragments of varying length as well as SARS-CoV, MERS-CoV, HCoV-OC43 and HCoV-NL63 proteins. IgG, IgA and IgM antibody responses to specific epitopes within the spike (S), nucleocapsid (N) and membrane proteins (M) were higher in older adult patients. Moreover, the older age group displayed more consistent correlations of antibody reactivity with systemic cytokine and chemokine responses when compared to the younger adult group. A subset of patients, however, had little or no response to SARS-CoV-2 antigens and disproportionately severe clinical outcomes. Further characterization of these serosilent individuals with cytokine analysis revealed significant differences in IL-10, IL-15, IP-10, EGF and sCD40L levels when compared to seroreactive patients in the cohort.

2001 ◽  
Vol 46 (No. 9–10) ◽  
pp. 241-243 ◽  
Author(s):  
S. Rahman M ◽  
K. Baek B ◽  
T. Hong S ◽  
H. Lee J

The antibody responses to toxoids were measured to investigate whether Clostridium perfringens beta and epsilon toxoids induced protective humoral immune responses in buffalos. Total of 24 buffalos were divided into 4 groups (n = 6), beta toxoid, epsilon toxoid, combination and control groups. These buffalo groups were administered each of the designated toxoids. Immunizations in the beta and epsilon toxoid groups induced strong antibody responses. The neutralizing antibody titres from the beta and epsilon toxoid groups were equally log101.2 on day 21 after inoculation whereas there was no antibody titre detected from the control group. A statistically significant (P < 0.01) increase in antibody titre was observed from day 0 to day 14 and 21 after inoculation. The antibody production did not vary significantly due to day of inoculation and toxoid interactions.


2010 ◽  
Vol 18 (2) ◽  
pp. 298-304 ◽  
Author(s):  
E. K. Hoebe ◽  
S. H. Hutajulu ◽  
J. van Beek ◽  
S. J. Stevens ◽  
D. K. Paramita ◽  
...  

ABSTRACTWHO type III nasopharyngeal carcinoma (NPC) is highly prevalent in Indonesia and 100% associated with Epstein-Barr virus (EBV). NPC tumor cells express viral proteins, including BARF1, which is secreted and is considered to have oncogenic and immune-modulating properties. Recently, we found conserved mutations in the BARF1 gene in NPC isolates. This study describes the expression and purification of NPC-derived BARF1 and analyzes humoral immune responses against prototype BARF1 (B95-8) and purified native hexameric BARF1 in sera of Indonesian NPC patients (n= 155) compared to healthy EBV-positive (n= 56) and EBV-negative (n= 16) individuals. BARF1 (B95-8) expressed inEscherichia coliand baculovirus, as well as BARF1-derived peptides, did not react with IgG or IgA antibodies in NPC. Purified native hexameric BARF1 protein isolated from culture medium was used in enzyme-linked immunosorbent assay (ELISA) and revealed relatively weak IgG and IgA responses in human sera, although it had strong antibody responses to other EBV proteins. Higher IgG reactivity was found in NPC patients (P= 0.015) than in regional Indonesian controls or EBV-negative individuals (P< 0.001). IgA responses to native BARF1 were marginal. NPC sera with the highest IgG responses to hexameric BARF1 in ELISA showed detectable reactivity with denatured BARF1 by immunoblotting. In conclusion, BARF1 has low immunogenicity for humoral responses and requires native conformation for antibody binding. The presence of antibodies against native BARF1 in the blood of NPC patients provides evidence that the protein is expressed and secreted as a hexameric protein in NPC patients.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Helen Parry ◽  
Gokhan Tut ◽  
Rachel Bruton ◽  
Sian Faustini ◽  
Christine Stephens ◽  
...  

Age is the major risk factor for mortality after SARS-CoV-2 infection and older people have received priority consideration for COVID-19 vaccination. However, vaccine responses are often suboptimal in this age group and few people over the age of 80 years were included in vaccine registration trials. We determined the serological and cellular response to spike protein in 100 people aged 80–96 years at 2 weeks after the second vaccination with the Pfizer BNT162b2 mRNA vaccine. Antibody responses were seen in every donor with high titers in 98%. Spike-specific cellular immune responses were detectable in only 63% and correlated with humoral response. Previous SARS-CoV-2 infection substantially increased antibody responses after one vaccine and antibody and cellular responses remained 28-fold and 3-fold higher, respectively, after dual vaccination. Post-vaccine sera mediated strong neutralization of live Victoria infection and although neutralization titers were reduced 14-fold against the P.1 variant first discovered in Brazil they remained largely effective. These data demonstrate that the mRNA vaccine platform delivers strong humoral immunity in people up to 96 years of age and retains broad efficacy against the P.1 variant of concern.


2000 ◽  
Vol 20 (15) ◽  
pp. 5363-5369 ◽  
Author(s):  
Klaus-Peter Knobeloch ◽  
Mark D. Wright ◽  
Adrian F. Ochsenbein ◽  
Oliver Liesenfeld ◽  
Jürgen Löhler ◽  
...  

ABSTRACT CD37 is a membrane protein of the tetraspanin superfamily, which includes CD9, CD53, CD63, CD81, and CD82. Many of these molecules are expressed on leukocytes and have been implicated in signal transduction, cell-cell interactions, and cellular activation and development. We generated and analyzed mice deficient for CD37. Despite the high expression of CD37 on cells of the immune system, no changes in development and cellular composition of lymphoid organs were observed in mice lacking CD37. Analyses of humoral immune responses revealed a reduced level of immunoglobulin G1 (IgG1) in the sera of nonimmunized mice and an alteration of responses to T-cell-dependent antigens. Antibody responses to model antigen administered in the absence of adjuvant and to viral infections were generally poor in CD37-deficient mice. These poor antibody responses could be overcome by the immunization of antigen together with adjuvant. These results suggest a role for CD37 in T-cell–B-cell interactions which manifests itself under suboptimal costimulatory conditions.


1999 ◽  
Vol 67 (8) ◽  
pp. 3937-3946 ◽  
Author(s):  
Spencer R. Hedges ◽  
Matthew S. Mayo ◽  
Jiri Mestecky ◽  
Edward W. Hook ◽  
Michael W. Russell

ABSTRACT Repeated infections with Neisseria gonorrhoeae are common among patients attending sexually transmitted disease clinics. We examined whether previous infections or site of infection altered the local and systemic antigonococcal antibody levels in males and females. Antibodies against N. gonorrhoeae MS11 and the patients’ homologous infecting isolates were measured by enzyme-linked immunosorbent assay. In general, the local and systemic immune responses to gonococci were extremely modest. There was a slight increase in serum immunoglobulin G (IgG) against the MS11 strain and the homologous isolates in infected males. Levels of serum IgA1 antibodies against MS11 were slightly higher in infected than in uninfected females. A history of previous infections with N. gonorrhoeae did not alter the antibody levels in patients with a current infection, suggesting that immunological memory is not induced by uncomplicated gonococcal infections. Antibody responses to infected subjects’ homologous isolates were observed in cervical mucus; IgA1 levels increased while IgG levels decreased. The decline in mucosal IgG against the homologous isolates was less common in subjects having both rectal and cervical infections; otherwise, no effect of rectal involvement was observed. The absence of substantially higher antibody levels to gonococci where there is infection at a site known to contain organized lymphoid tissue suggests that the low levels of responses to uncomplicated infections may not be due simply to an absence of inductive sites in the genital tract. We propose that in addition to its potential ability to avoid the effects of an immune response,N. gonorrhoeae does not elicit strong humoral immune responses during uncomplicated genital infections.


1981 ◽  
Vol 98 (4) ◽  
pp. 506-513 ◽  
Author(s):  
Istvan Berczi ◽  
Eva Nagy ◽  
Kalman Kovacs ◽  
Eva Horvath

Abstract. Hypophysectomized female Fischer 344 and Wistar-Furth rats had severely impaired primary and secondary antibody responses to sheep red blood cells (SRBC). Mercaptoethanol-sensitive (IgM) and mercaptoethanol-resistant (IgG) antibodies were similarly affected. Titers to E. Coli 055:B5 lipopolysaccharide were also significantly decreased in such animals. The antibody response of hypophysectomized rats could be restored by syngeneic pituitary grafts when placed under the kidney capsule or by prolactin treatment. Growth hormone was less effective in this respect than prolactin. Treatment of normal rats with ACTH suppressed their antibody formation to SRBC. These results indicate that the pituitary gland has the potential to regulate humoral immune responses.


2001 ◽  
Vol 69 (12) ◽  
pp. 7437-7444 ◽  
Author(s):  
Austin Vaz ◽  
Lisa Glickstein ◽  
Jodie A. Field ◽  
Gail McHugh ◽  
Vijay K. Sikand ◽  
...  

ABSTRACT We determined cellular and humoral immune responses toBorrelia burgdorferi lysate and to recombinant flagellin (FlaB), OspC, and OspA in acute- and convalescent-phase samples from 39 culture-positive patients with erythema migrans and in 20 healthy control subjects. During the acute illness, a median of 4 days after the onset of erythema migrans, 51% of the patients had proliferative cellular responses and 72% had antibody responses to at least one of the borrelial antigens tested. During convalescence, at the conclusion of antibiotic therapy, 64% of the patients had proliferative cellular reactivity and 95% had antibody reactivity with at least one of the spirochetal antigens tested. In both acute- and convalescent-phase samples, cellular immune responses were found as frequently to OspA as to OspC and FlaB. Although antibody responses were also frequently seen to OspC and FlaB, only a few patients had marginal antibody reactivity with OspA. The percentage of patients with proliferative responses was similar in those with clinical evidence of localized or disseminated infection, whereas humoral reactivity was found more often in those with disseminated disease. We conclude that cellular and humoral responses to B. burgdorferi antigens are often found among patients with early Lyme disease. In contrast with the other antigens tested, cellular but not humoral reactivity was often found with OspA.


2006 ◽  
Vol 203 (3) ◽  
pp. 599-606 ◽  
Author(s):  
Silvia B. Boscardin ◽  
Julius C.R. Hafalla ◽  
Revati F. Masilamani ◽  
Alice O. Kamphorst ◽  
Henry A. Zebroski ◽  
...  

Resistance to several prevalent infectious diseases requires both cellular and humoral immune responses. T cell immunity is initiated by mature dendritic cells (DCs) in lymphoid organs, whereas humoral responses to most antigens require further collaboration between primed, antigen-specific helper T cells and naive or memory B cells. To determine whether antigens delivered to DCs in lymphoid organs induce T cell help for antibody responses, we targeted a carrier protein, ovalbumin (OVA), to DCs in the presence of a maturation stimulus and assayed for antibodies to a hapten, (4-hydroxy-3-nitrophenyl) acetyl (NP), after boosting with OVA-NP. A single DC-targeted immunization elicited long-lived T cell helper responses to the carrier protein, leading to large numbers of antibody-secreting cells and high titers of high-affinity antihapten immunoglobulin Gs. Small doses of DC-targeted OVA induced higher titers and a broader spectrum of anti-NP antibody isotypes than large doses of OVA in alum adjuvant. Similar results were obtained when the circumsporozoite protein of Plasmodium yoelii was delivered to DCs. We conclude that antigen targeting to DCs combined with a maturation stimulus produces broad-based and long-lived T cell help for humoral immune responses.


2021 ◽  
Author(s):  
Daniel M. Williams ◽  
Hayley Hornsby ◽  
Ola M. Shehata ◽  
Rebecca Brown ◽  
Domen Zafred ◽  
...  

The strong humoral immune response produced against the SARS-CoV-2 nucleocapsid (N) and spike (S) proteins has underpinned serological testing but the prevalence of antibody responses to other SARS-CoV-2 proteins, which may be of use as further serological markers, is still unclear. Cell-based serological screening platforms can fulfil a crucial niche in the identification of antibodies which recognise more complex folded epitopes or those incorporating post-translation modifications which may be undetectable by other methods used to investigate the antigenicity of the SARS-CoV-2 proteome. Here, we employed automated high content immunofluorescence microscopy (AHCIM) to assess the viability of such an approach as a method capable of assaying humoral immune responses against full length SARS-CoV-2 proteins in their native cellular state. We first demonstrate that AHCIM provides high sensitivity and specificity in the detection of SARS-CoV-2 N and S IgG. Assessing the prevalence of antibody responses to the SARS-CoV-2 structural membrane protein (M), we further find that 85% of COVID-19 patients within our sample set developed detectable M IgG responses (M sensitivity 85%, N sensitivity 93%, combined N + M sensitivity 95%). The identification of M as a serological marker of high prevalence may be of value in detecting additional COVID-19 cases during the era of mass SARS-CoV-2 vaccinations, where serological screening for SARS CoV-2 infections in vaccinated individuals is dependent on detection of antibodies against N. These findings highlight the advantages of using cell-based systems as serological screening platforms and raise the possibility of using M as a widespread serological marker alongside N and S.


2021 ◽  
Author(s):  
Carolina Garrido ◽  
Jillian H Hurst ◽  
Cynthia G. Lorang ◽  
Jhoanna N. Aquino ◽  
Javier Rodriguez ◽  
...  

As SARS-CoV-2 continues to spread globally, questions have emerged regarding the strength and durability of immune responses in specific populations. In this study, we evaluated humoral immune responses in 69 children and adolescents with asymptomatic or mild symptomatic SARS-CoV-2 infection. We detected robust IgM, IgG, and IgA antibody responses to a broad array of SARS-CoV-2 antigens at the time of acute infection and 2 and 4 months after acute infection in all participants. Notably, these antibody responses were associated with virus neutralizing activity that was still detectable 4 months after acute infection in 94% of children. Moreover, antibody responses and neutralizing activity in sera from children and adolescents were comparable or superior to those observed in sera from 24 adults with mild symptomatic infection. Taken together, these findings indicate children and adolescents with mild or asymptomatic SARS-CoV-2 infection generate robust and durable humoral immune responses that are likely to protect from reinfection.


Sign in / Sign up

Export Citation Format

Share Document