Humoral immune responses during SARS-CoV-2 mRNA vaccine administration in seropositive and seronegative individuals

Abstract Background The global pandemic of coronavirus disease 2019 (COVID-19) is caused by infection with the SARS-CoV-2 virus. Currently, there are three approved vaccines against SARS-CoV-2 in the USA, including two based on messenger RNA (mRNA) technology that has demonstrated high vaccine efficacy. We sought to characterize humoral immune responses, at high resolution, during immunization with the BNT162b2 (Pfizer-BioNTech) vaccine in individuals with or without prior history of natural SARS-CoV-2 infection. Methods We determined antibody responses after each dose of the BNT162b2 SARS-CoV-2 vaccine in individuals who had no prior history of SARS-CoV-2 infection (seronegative) and individuals that had previous viral infection 30–60 days prior to first vaccination (seropositive). To do this, we used both an antibody isotype-specific multiplexed bead-based binding assays targeting multiple SARS-CoV-2 viral protein antigens and an assay that identified potential SARS-CoV-2 neutralizing antibody levels. Moreover, we mapped antibody epitope specificity after immunization using SARS-CoV-2 spike protein peptide arrays. Results Antibody levels were significantly higher after a single dose in seropositive individuals compared to seronegative individuals and were comparable to levels observed in seronegative individuals after two doses. While IgG was boosted by vaccination for both seronegative and seropositive individuals, only seronegative individuals had increased IgA or IgM antibody titers after primary immunization. We identified immunodominant peptides targeted on both SARS-CoV-2 spike S1 and S2 subunits after vaccination. Conclusion These findings demonstrated the antibody responses to SARS-CoV-2 immunization in seropositive and seronegative individuals and provide support for the concept of using prior infection history as a guide for the consideration of future vaccination regimens. Moreover, we identified key epitopes on the SARS-CoV-2 spike protein that are targeted by antibodies after vaccination that could guide future vaccine and immune correlate development.

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Limited Local and Systemic Antibody Responses toNeisseria gonorrhoeae during Uncomplicated Genital Infections

Infection and Immunity ◽

10.1128/iai.67.8.3937-3946.1999 ◽

1999 ◽

Vol 67 (8) ◽

pp. 3937-3946 ◽

Cited By ~ 77

Author(s):

Spencer R. Hedges ◽

Matthew S. Mayo ◽

Jiri Mestecky ◽

Edward W. Hook ◽

Michael W. Russell

Keyword(s):

Immune Responses ◽

Transmitted Disease ◽

Antibody Responses ◽

Enzyme Linked Immunosorbent Assay ◽

Genital Infections ◽

Sexually Transmitted ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Repeated Infections ◽

Antibody Levels

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.

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Vaccination strategy and anti - SARS-CoV-2 S titers in healthcare workers of the INT – IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy)

Infectious Agents and Cancer ◽

10.1186/s13027-021-00375-2 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Ernesta Cavalcanti ◽

Maria Antonietta Isgrò ◽

Domenica Rea ◽

Lucia Di Capua ◽

Giusy Trillò ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Healthcare Workers ◽

Geometric Mean ◽

Vaccination Strategy ◽

Antibody Responses ◽

Cancer Center ◽

Serum Samples ◽

Humoral Immune ◽

History Of

Abstract Background Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and the resulting disease, coronavirus disease 2019 (COVID-19), have spread to millions of people globally, requiring the development of billions of different vaccine doses. The SARS-CoV-2 spike mRNA vaccine (named BNT162b2/Pfizer), authorized by the FDA, has shown high efficacy in preventing SARS-CoV-2 infection after administration of two doses in individuals 16 years of age and older. In the present study, we retrospectively evaluated the differences in the SARS-CoV-2 humoral immune response after vaccine administration in the two different cohorts of workers at the INT - IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy): previously infected to SARS-CoV-2 subjects and not infected to SARS-CoV-2 subjects. Methods We determined specific anti-RBD (receptor-binding domain) titers against trimeric spike glycoprotein (S) of SARS-CoV-2 by Roche Elecsys Anti-SARS-CoV-2 S immunoassay in serum samples of 35 healthcare workers with a previous documented history of SARS-CoV-2 infection and 158 healthcare workers without, after 1 and 2 doses of vaccine, respectively. Moreover, geometric mean titers and relative fold changes (FC) were calculated. Results Both previously infected and not infected to SARS-CoV-2 subjects developed significant immune responses to SARS-CoV-2 after the administration of 1 and 2 doses of vaccine, respectively. Anti-S antibody responses to the first dose of vaccine were significantly higher in previously SARS-CoV-2-infected subjects in comparison to titers of not infected subjects after the first as well as the second dose of vaccine. Fold changes for subjects previously infected to SARS-CoV-2 was very modest, given the high basal antibody titer, as well as the upper limit of 2500.0 BAU/mL imposed by the Roche methods. Conversely, for naïve subjects, mean fold change following the first dose was low ($$ \overline{x} $$ x ¯ =1.6), reaching 3.8 FC in 72 subjects (45.6%) following the second dose. Conclusions The results showed that, as early as the first dose, SARS-CoV-2-infected individuals developed a remarkable and statistically significant immune response in comparison to those who did not contract the virus previously, suggesting the possibility of administering only one dose in previously SARS-CoV-2-infected subjects. FC for previously infected subjects should not be taken into account for the generally high pre-vaccination values. Conversely, FC for not infected subjects, after the second dose, were = 3.8 in > 45.0% of vaccinees, and ≤ 3.1 in 19.0%, the latter showing a potential susceptibility to further SARS-CoV-2 infection.

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Adenoviral expression of a truncated S1 subunit of SARS-CoV spike protein results in specific humoral immune responses against SARS-CoV in rats

Virus Research ◽

10.1016/j.virusres.2005.02.009 ◽

2005 ◽

Vol 112 (1-2) ◽

pp. 24-31 ◽

Cited By ~ 35

Author(s):

Ran-Yi Liu ◽

Li-Zhi Wu ◽

Bi-Jun Huang ◽

Jia-Ling Huang ◽

Yan-Ling Zhang ◽

...

Keyword(s):

Immune Responses ◽

Spike Protein ◽

Humoral Immune ◽

Humoral Immune Responses

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mRNA vaccination in people over 80 years of age induces strong humoral immune responses against SARS-CoV-2 with cross neutralization of P.1 Brazilian variant

eLife ◽

10.7554/elife.69375 ◽

2021 ◽

Vol 10 ◽

Author(s):

Helen Parry ◽

Gokhan Tut ◽

Rachel Bruton ◽

Sian Faustini ◽

Christine Stephens ◽

...

Keyword(s):

Immune Responses ◽

Cellular Response ◽

Humoral Response ◽

Antibody Responses ◽

Vaccine Platform ◽

Humoral Immune ◽

Vaccine Responses ◽

Cellular Immune Responses ◽

Humoral Immune Responses ◽

Cellular Immune

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.

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The in vivo function of a noncanonical TRAF2-binding domain in the C-terminus of CD40 in driving B-cell growth and differentiation

Blood ◽

10.1182/blood-2006-07-038414 ◽

2007 ◽

Vol 110 (1) ◽

pp. 193-200 ◽

Cited By ~ 18

Author(s):

Li-Fan Lu ◽

Cory L. Ahonen ◽

Evan F. Lind ◽

Vanitha S. Raman ◽

W. James Cook ◽

...

Keyword(s):

Immune Responses ◽

B Cell ◽

Cell Activation ◽

Affinity Maturation ◽

Functional Domain ◽

Antibody Isotype ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Cell Immunity

The recruitment of tumor necrosis factor receptor–associated factors (TRAFs) 1, 2, 3, 5, and 6 to the CD40 cytoplasmic tail upon CD40 trimerization results in downstream signaling events that ultimately lead to CD40-dependent, thymus-dependent (TD) humoral immune responses. Previously, we have shown signaling through the C-terminal tail of CD40 in the absence of canonical TRAF-binding sites is capable of signaling through an alternative TRAF2-binding site. Here, we demonstrate that B cells from mice harboring CD40 with only the C-terminal tail can activate both canonical and noncanonical NFκB signaling pathways. Moreover, while lacking germinal center formation, several hallmarks of humoral immune responses including clonal B-cell activation/expansion, antibody isotype switching, and affinity maturation remain normal. This study demonstrates a new functional domain in CD40 that controls critical aspects of B-cell immunity in an in vivo setting.

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Similar humoral immune responses against the SARS-CoV-2 spike protein in HIV and non-HIV individuals after COVID-19

Journal of Infection ◽

10.1016/j.jinf.2021.11.002 ◽

2021 ◽

Author(s):

María Martín-Vicente ◽

Juan Berenguer ◽

María José Muñoz-Gómez ◽

Cristina Díez ◽

Rafael Micán ◽

...

Keyword(s):

Immune Responses ◽

Spike Protein ◽

Humoral Immune ◽

Humoral Immune Responses

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Regulation of humoral immunity in rats by pituitary hormones

Acta Endocrinologica ◽

10.1530/acta.0.0980506 ◽

1981 ◽

Vol 98 (4) ◽

pp. 506-513 ◽

Cited By ~ 159

Author(s):

Istvan Berczi ◽

Eva Nagy ◽

Kalman Kovacs ◽

Eva Horvath

Keyword(s):

Immune Responses ◽

Antibody Formation ◽

Pituitary Hormones ◽

Antibody Responses ◽

Igg Antibodies ◽

E Coli ◽

Humoral Immune ◽

Fischer 344 ◽

Humoral Immune Responses ◽

Hypophysectomized Rats

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.

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Cellular and Humoral Immune Responses toBorrelia burgdorferi Antigens in Patients with Culture-Positive Early Lyme Disease

Infection and Immunity ◽

10.1128/iai.69.12.7437-7444.2001 ◽

2001 ◽

Vol 69 (12) ◽

pp. 7437-7444 ◽

Cited By ~ 51

Author(s):

Austin Vaz ◽

Lisa Glickstein ◽

Jodie A. Field ◽

Gail McHugh ◽

Vijay K. Sikand ◽

...

Keyword(s):

Lyme Disease ◽

Immune Responses ◽

Erythema Migrans ◽

Antibody Responses ◽

Humoral Immune ◽

Convalescent Phase ◽

Humoral Immune Responses ◽

Antibody Reactivity ◽

Disseminated Disease ◽

Culture Positive

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.

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Diverse humoral immune responses and changes in IgG antibody levels against mycobacterial lipid antigens in active tuberculosis

Microbiology ◽

10.1099/mic.0.27790-0 ◽

2005 ◽

Vol 151 (6) ◽

pp. 2065-2074 ◽

Cited By ~ 24

Author(s):

Yukiko Fujita ◽

Takeshi Doi ◽

Koji Sato ◽

Ikuya Yano

Keyword(s):

Immune Responses ◽

Response Patterns ◽

Igg Antibody ◽

Lipid Antigens ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Antigen Elisa ◽

Positive Rate ◽

Smear Negative ◽

Antibody Levels

Humoral immune responses of active TB patients against six mycobacterial lipid antigens [trehalose 6,6′-dimycolate (TDM) from Mycobacterium bovis BCG (TDM-T) and Mycobacterium avium complex (TDM-M), trehalose 6-monomycolate (TMM) from M. bovis BCG (TMM-T) and M. avium complex (TMM-M), triacyl (PL-2) and tetraacyl (PL-1) phosphatidylinositol dimannosides] were examined by ELISA. IgG antibodies of TB patients with active disease reacted against the six lipid antigens distinctively, but heterogeneously. If tests were combined and an overall positive was scored cumulatively when any one of the six tests was positive, a good discrimination between patient and normal subject was obtained. A positive result in any one of the six tests was obtained in 91·5 % of all 924 hospitalized patients and 93·3 % of 210 patients at their first visit to the outpatient clinic. The IgG antibody response differed considerably from patient to patient, and the response patterns were grouped into several types. IgG antibody levels paralleled the bacterial burden; however, the smear-negative (culture-positive) patient group also showed high positive rates and mean ELISA ΔA values against the six lipid antigens. There were also marked differences in positive rate and mean ΔA values between cavity-positive and -negative groups, the former being higher than the latter. After anti-TB chemotherapy was initiated, IgG antibody levels decreased dramatically, paralleling the decrease in the amount of excretion of bacteria. Since multiple-antigen ELISA using particular lipid antigens was highly sensitive, and IgG antibody levels vary greatly at different stages of the disease, this technique is applicable for early diagnosis of smear-negative (and -positive) active TB and the prognosis for completion of anti-TB chemotherapy.

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Antigen targeting to dendritic cells elicits long-lived T cell help for antibody responses

Journal of Experimental Medicine ◽

10.1084/jem.20051639 ◽

2006 ◽

Vol 203 (3) ◽

pp. 599-606 ◽

Cited By ~ 182

Author(s):

Silvia B. Boscardin ◽

Julius C.R. Hafalla ◽

Revati F. Masilamani ◽

Alice O. Kamphorst ◽

Henry A. Zebroski ◽

...

Keyword(s):

Dendritic Cells ◽

T Cell ◽

Immune Responses ◽

Lymphoid Organs ◽

Antibody Responses ◽

Carrier Protein ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Maturation Stimulus ◽

T Cell Help

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.

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