Functional convalescent plasma antibodies and pre-infusion titers shape the early severe COVID-19 immune response

AbstractTransfer of convalescent plasma (CP) had been proposed early during the SARS-CoV-2 pandemic as an accessible therapy, yet trial results worldwide have been mixed, potentially due to the heterogeneous nature of CP. Here we perform deep profiling of SARS-CoV-2-specific antibody titer, Fc-receptor binding, and Fc-mediated functional assays in CP units, as well as in plasma from hospitalized COVID-19 patients before and after CP administration. The profiling results show that, although all recipients exhibit expanded SARS-CoV-2-specific humoral immune responses, CP units contain more functional antibodies than recipient plasma. Meanwhile, CP functional profiles influence the evolution of recipient humoral immunity in conjuncture with the recipient’s pre-existing SARS-CoV2-specific antibody titers: CP-derived SARS-CoV-2 nucleocapsid-specific antibody functions are associated with muted humoral immune evolution in patients with high titer anti-spike IgG. Our data thus provide insights into the unexpected impact of CP-derived functional anti-spike and anti-nucleocapsid antibodies on the evolution of SARS-CoV-2-specific response following severe infection.

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Subtle immunological differences in mRNA-1273 and BNT162b2 COVID-19 vaccine induced Fc-functional profiles

10.1101/2021.08.31.458247 ◽

2021 ◽

Author(s):

Paulina Kaplonek ◽

Deniz Cizmeci ◽

Stephanie Fischinger ◽

Ai-ris Collier ◽

Todd Suscovich ◽

...

Keyword(s):

Immune Responses ◽

Specific Antibody ◽

Neutralizing Antibodies ◽

Humoral Response ◽

Hospital Staff ◽

Differential Protection ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Functional Antibodies ◽

Functional Profiles

The successful development of several COVID-19 vaccines has substantially reduced morbidity and mortality in regions of the world where the vaccines have been deployed. However, in the wake of the emergence of viral variants, able to evade vaccine induced neutralizing antibodies, real world vaccine efficacy has begun to show differences across the mRNA platforms, suggesting that subtle variation in immune responses induced by the BNT162b2 and mRNA1273 vaccines may provide differential protection. Given our emerging appreciation for the importance of additional antibody functions, beyond neutralization, here we profiled the post-boost binding and functional capacity of the humoral response induced by the BNT162b2 and mRNA-1273 in a cohort of hospital staff. Both vaccines induced robust humoral immune responses to WT SARS-CoV-2 and VOCs. However, differences emerged across epitope-specific responses, with higher RBD- and NTD- specific IgA, as well as functional antibodies (ADNP and ADNK) in mRNA-1273 vaccine recipients. Additionally, RBD-specific antibody depletion highlighted the different roles of non-RBD-specific antibody effector function induced across the mRNA vaccines, providing novel insights into potential differences in protective immunity generated across these vaccines in the setting of newly emerging VOCs.

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Immunological Distinctions between Acellular and Whole-Cell Pertussis Immunizations of Baboons Persist for at Least One Year after Acellular Vaccine Boosting

Vaccines ◽

10.3390/vaccines8040729 ◽

2020 ◽

Vol 8 (4) ◽

pp. 729

Author(s):

Leah E. Cole ◽

Jinrong Zhang ◽

Kristl M. Pacheco ◽

Philippe Lhéritier ◽

Natalie G. Anosova ◽

...

Keyword(s):

Immune Responses ◽

Disease Burden ◽

Memory B Cells ◽

Whole Cell ◽

Humoral Immune ◽

Serum Bactericidal Activity ◽

Humoral Immune Responses ◽

Specific Memory ◽

Antibody Titers ◽

One Year

While both whole-cell (wP) and acellular pertussis (aP) vaccines have been highly effective at reducing the global pertussis disease burden, there are concerns that compared to wP vaccination, the immune responses to aP vaccination may wane more rapidly. To gain insights into the vaccine elicited immune responses, pre-adult baboons were immunized with either aP or wP vaccines, boosted with an aP vaccine, and observed over a nearly two-year period. Priming with a wP vaccine elicited a more Th17-biased response than priming with aP, whereas priming with an aP vaccine led to a more Th2-biased response than priming with wP. These differences were maintained after aP vaccine boost immunizations. Compared to aP, animals primed with a wP vaccine exhibited greater numbers of pertussis specific memory B cells. While aP and wP vaccine priming initially elicited similar levels of anti-pertussis toxin antibody, titers declined more rapidly in aP vaccine primed animals leading to a 4-fold difference. Both wP and aP vaccine immunization could induce serum bactericidal activity (SBA); however, only one wP vaccine immunization was required to elicit SBA while multiple aP vaccine immunizations were required to elicit lower, less durable SBA titers. In conclusion, when compared to aP vaccine, priming with wP vaccine elicits distinct cellular and humoral immune responses that persist after aP vaccine boosting.

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Durability of Antibody Responses to SARS-CoV-2 Infection and Its Relationship to Disease Severity Assessed Using a Commercially Available Assay

Frontiers in Microbiology ◽

10.3389/fmicb.2021.770727 ◽

2021 ◽

Vol 12 ◽

Author(s):

Alanoud Alshami ◽

Rabab Al Attas ◽

Hadeel Anan ◽

Aroub Al Maghrabi ◽

Salim Ghandorah ◽

...

Keyword(s):

Disease Severity ◽

Seroconversion Rate ◽

Strongly Correlated ◽

Icu Patients ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Asymptomatic Patients ◽

Antibody Titers ◽

Polymerase Chain ◽

Antibody Dynamics

Background: Assessing the humoral immune response to SARS-CoV-2 is crucial for inferring protective immunity from reinfection and for assessing vaccine efficacy. Data regarding the durability and sustainability of SARS-CoV-2 antibodies are conflicting. In this study, we aimed to determine the seroconversion rate of SARS-CoV-2 infection in a cohort of reverse-transcriptase polymerase chain reaction (RT–PCR)-confirmed SARS-CoV-2 infections and the antibody dynamics, durability, and the correlation of antibody titers with disease severity using the commercially available SARS-CoV-2 anti-spike (S1/S2) protein.Methods: A total of 342 subjects with PCR-confirmed COVID-19 were enrolled. A total of 395 samples were collected at different time points (0–204) after the onset of symptoms or from the day of positive PCR in asymptomatic patients. Demographics, clinical presentation and the date of PCR were collected. All samples were tested using the automated commercial chemiluminescent system (DiaSorin SARS-CoV-2 S1/S2 IgG) on the LIAISONXL® platform (LIAISON).Results: The seroconversion rate for samples collected 14 days after the onset of infection was much higher than that for samples collected before 14 days (79.4% vs. 39.4%). The rate of seroconversion in symptomatic participants (62.1%) was similar to that of asymptomatic participants (56.1%) (p = 0.496). The IgG titer distribution was also similar across both groups (p = 0.142), with a median IgG level of 27.86 AU/ml (3.8–85.5) and 15 AU/ml (3.8–58.85) in symptomatic and asymptomatic participants, respectively. However, IgG titers were significantly higher in ICU patients, with a median of 104 AU/ml (3.8–179) compared to 34 AU/ml (3.8–70) in the non-ICU participants (p < 0.0001). Furthermore, the median time to seroconversion occurred significantly faster in ICU patients than in non-ICU participants (19 versus 47 days) (P < 0.0001). IgG titers were also higher in subjects ≥50 years compared to those <50 years (p < 0.009), male compared to female (p < 0.054) and non-Saudi compared to Saudi (p < 0.003). Approximately 74% of all samples tested beyond 120 days were positive.Conclusion: Antibodies can persist in circulation for longer than 4 months after COVID-19 infection. The majority of patients with COVID-19 mounted humoral immune responses to SARS-CoV-2 infection that strongly correlated with disease severity, older age and male gender. However, the population of individuals who tested negative should be further evaluated.

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Modulations on inflammatory and humoral immune responses to oxidized LDL and apolipoprotein B-100 epitope before and after coronary angioplasty

Hellenic Journal of Cardiology ◽

10.1016/j.hjc.2020.08.001 ◽

2020 ◽

Author(s):

Viviane Aparecida Rodrigues Sant’Anna ◽

Rodrigo Almeida Souza ◽

Adriano Henrique Pereira Barbosa ◽

José Marconi Almeida Sousa ◽

Antônio Carlos de Camargo Carvalho ◽

...

Keyword(s):

Immune Responses ◽

Coronary Angioplasty ◽

Apolipoprotein B ◽

Oxidized Ldl ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Before And After

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Effect of mannanoligosaccharides and/or enzymes on antibody titers against infectious bursal and Newcastle disease viruses

Arquivo Brasileiro de Medicina Veterinária e Zootecnia ◽

10.1590/s0102-09352009000100002 ◽

2009 ◽

Vol 61 (1) ◽

pp. 6-11 ◽

Cited By ~ 13

Author(s):

M.C. Oliveira ◽

D.F. Figueiredo-Lima ◽

D.E. Faria Filho ◽

R.H. Marques ◽

V.M.B. Moraes

Keyword(s):

Immune Responses ◽

Disease Virus ◽

Newcastle Disease ◽

Control Diet ◽

Positive Control ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Randomized Experimental Design ◽

Bursal Disease ◽

Antibody Titers

The effect of including mannanoligosaccharides (MOS) and/or enzymes in broiler diets on antibody titers against infectious bursal disease virus (IBDV) and Newcastle disease virus (NDV) was evaluated. A total of 750 broilers were distributed into a completely randomized experimental design in a factorial arrangement 2 x 2 + 1 with two levels of MOS (0 and 0.1% until 21 days and 0.05% from 22 to 42 days of age), two levels of enzymes (0 and 0.05%) and a positive control diet containing antibiotic, totaling five treatments with five replicates each. For antibody analyses, blood samples were weekly collected by jugular vein puncture in the same two birds per replicate. The first and last collections were done at 7 and 42 days of age, respectively. The inclusion of MOS resulted in increased antibody titers against IBDV in the fourth (P<0.03) and fifth (P<0.02) weeks, and against NDV in the third (P<0.01), fourth (P<0.03) and fifth (P<0.03) weeks of age. MOS was effective in stimulating the humoral immune responses against IBDV and NDV vaccine viruses.

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Rubella virus-specific humoral immune responses and their interrelationships before and after a third dose of measles-mumps-rubella vaccine in women of childbearing age

Vaccine ◽

10.1016/j.vaccine.2019.11.004 ◽

2020 ◽

Vol 38 (5) ◽

pp. 1249-1257 ◽

Cited By ~ 2

Author(s):

Iana H. Haralambieva ◽

Inna G. Ovsyannikova ◽

Richard B. Kennedy ◽

Krista M. Goergen ◽

Diane E. Grill ◽

...

Keyword(s):

Immune Responses ◽

Rubella Virus ◽

Women Of Childbearing Age ◽

Childbearing Age ◽

Rubella Vaccine ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Before And After

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Potent SARS-CoV-2-Specific T Cell Immunity and Low Anaphylatoxin Levels Correlate With Mild Disease Progression in COVID-19 Patients

Frontiers in Immunology ◽

10.3389/fimmu.2021.684014 ◽

2021 ◽

Vol 12 ◽

Author(s):

Eliott Lafon ◽

Gabriel Diem ◽

Christina Witting ◽

Viktoria Zaderer ◽

Rosa Maria Bellmann-Weiler ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Immune Responses ◽

Disease Progression ◽

Color Flow ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Cell Immunity ◽

Antibody Titers ◽

Anaphylatoxin C3a

T cells play a fundamental role in the early control and clearance of many viral infections of the respiratory system. In SARS-CoV-2-infected individuals, lymphopenia with drastically reduced CD4+ and CD8+ T cells correlates with Coronavirus disease 2019 (COVID-19)-associated disease severity and mortality. In this study, we characterized cellular and humoral immune responses induced in patients with mild, severe and critical COVID-19. Peripheral blood mononuclear cells of 37 patients with mild, severe and critical COVID-19 and 10 healthy individuals were analyzed by IFNγ ELISpot and multi-color flow cytometry upon stimulation with peptide pools covering complete immunodominant SARS-CoV-2 matrix, nucleocapsid and spike proteins. In addition SARS-CoV-2 antibody levels, neutralization abilities and anaphylatoxin levels were evaluated by various commercially available ELISA platforms. Our data clearly demonstrates a significantly stronger induction of SARS-CoV-2 specific CD8+ T lymphocytes and higher IFNγ production in patients with mild compared to patients with severe or critical COVID-19. In all patients SARS-CoV-2-specific antibodies with similar neutralizing activity were detected, but highest titers of total IgGs were observed in critical patients. Finally, elevated anaphylatoxin C3a and C5a levels were identified in severe and critical COVID-19 patients probably caused by aberrant immune complex formation due to elevated antibody titers in these patients. Crucially, we provide a full picture of cellular and humoral immune responses of COVID-19 patients and prove that robust polyfunctional CD8+ T cell responses concomitant with low anaphylatoxin levels correlate with mild infections. In addition, our data indicates that high SARS-CoV-2 antibody titers are associated with severe disease progression.

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The effect of <i>Myrtus communis</i> oil extract on growth performance, serum biochemistry and humoral immune responses in broiler chicks fed diet containing aflatoxin B1

Archives Animal Breeding ◽

10.7482/0003-9438-56-084 ◽

2013 ◽

Vol 56 (1) ◽

pp. 842-850 ◽

Cited By ~ 3

Author(s):

M. M. Saei ◽

A. A. Sadeghi ◽

H. Ahmadvand

Keyword(s):

Immune Responses ◽

Growth Performance ◽

Aflatoxin B1 ◽

Broiler Chickens ◽

Serum Biochemistry ◽

Influenza Viruses ◽

Myrtus Communis ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Antibody Titers

Abstract. A study was conducted to investigate the capability of Myrtus communis essential oil (MCE) in counteracting the deleterious effects of aflatoxin B1 (AFB1) on growth performance, serum biochemistry and humoral immune responses in broiler chickens. In a completely randomized design, 300 day-old male chicks were assigned to four treatments with five replicates of 15 birds for 42 days. Chickens, up to day 7 of age, were fed the same diet and then, they were fed the experimental diets. The dietary treatments were 1) the negative control (no dietary aflatoxin or MCE), 2) the positive control (diet containing AFB1 at 0.5 mg/kg, without MCE), 3) diet containing AFB1 at 0.5 mg/kg plus 500 mg/kg MCE, and 4) basal diet containing 500 mg/kg MCE, without AFB1. Growth performance was measured from day 7 to 42. Serum biochemical parameters, organ weights on day 42 and the antibody titers against Newcastle and influenza viruses on day 28 of age were determined. Addition of aflatoxin to diet decreased (P<0.05) the weight gain and feed intake and MCE supplementation diminished (P<0.05) the inhibitory effects of AFB1 on the growth performance. Addition of AFB1 to diet of chicks increased the serum activities of aspartate aminotransferase (AST), alkaline aminotransferase (ALT), alkaline phosphatase (ALP), and decreased the antibody titers against Newcastle and influenza viruses. Addition of MCE to diet alleviated the negative effects of AFB1 on these parameters (P<0.05). In conclusion, our results showed that addition of MCE may reduce the adverse effects of AFB1 on broiler chickens.

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Specific IgA antibodies in the diagnosis of acute brucellosis

The Journal of Infection in Developing Countries ◽

10.3855/jidc.1411 ◽

2011 ◽

Vol 6 (02) ◽

pp. 192-200 ◽

Cited By ~ 1

Author(s):

Hanan El-Mohammady ◽

Hind Ibrahim Shaheen ◽

John David Klena ◽

Isabelle Antoun Nakhla ◽

Mattew A Weiner ◽

...

Keyword(s):

Disease Onset ◽

Immunoblot Analysis ◽

Acute Stage ◽

North African ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Before And After ◽

Night Sweats ◽

Weight Protein ◽

Immunogenic Proteins

An Egyptian female with night sweats, headache, and back pain was diagnosed with acute brucellosis one week after returning from a North African country. Humoral immune responses to specific immunogenic proteins were investigated before and after treatment. ELISA was performed to detect levels of specific antibody (Ab) titers. Immunoblot analysis of Ab recognizing specific Brucella antigenic bands was also performed. IgA was detected on the day of disease onset. Specific agglutination titer was 1:160; it doubled three days later and treatment was implemented. Blood culture yielded Gram-negative coccobacilli after one month, confirmed as B. melitensis by AMOS-PCR. Immunoblotting revealed IgM Abs against two protein bands of 112 and 130-kDa observed only during the acute stage. On the other hand, the intensity of IgG Abs against 21 and 21.5-kDa protein bands positively correlated with the time of convalescence. Based on our observations we conclude that specific IgA levels may be used as an early diagnostic marker for Brucella and high molecular weight protein bands may be useful in the differentiation between acute and chronic brucellosis.

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Live Oral Salmonella enterica Serovar Typhi Vaccines Ty21a and CVD 909 Induce Opsonophagocytic Functional Antibodies in Humans That Cross-React withS. Paratyphi A andS. Paratyphi B

Clinical and Vaccine Immunology ◽

10.1128/cvi.00786-13 ◽

2014 ◽

Vol 21 (3) ◽

pp. 427-434 ◽

Cited By ~ 30

Author(s):

Rezwanul Wahid ◽

Shah J. Zafar ◽

Monica A. McArthur ◽

Marcela F. Pasetti ◽

Myron M. Levine ◽

...

Keyword(s):

Salmonella Enterica ◽

Content Type ◽

Before And After ◽

Human Sera ◽

Antibody Titers ◽

Paratyphi B ◽

Iga Antibody ◽

Functional Antibodies ◽

New Generation

ABSTRACTLive oralSalmonella entericaserovar Typhi vaccine Ty21a induces specific antibodies that cross-react againstSalmonella entericaserovar Paratyphi A andSalmonella entericaserovar Paratyphi B, although their functional role in clearance remains unknown. We utilized anin vitroassay with THP-1 macrophages to compare the phagocytosis and survival ofSalmonellaopsonized with heat-inactivated human sera obtained before and after vaccination with Ty21a or a live oralS. Typhi vaccine, CVD 909. Opsonization with postvaccination sera predominantly increased the phagocytosis ofS. Typhi relative to the corresponding prevaccination sera, and increases were also observed withS. Paratyphi A andS. Paratyphi B, albeit of lower magnitudes. Relative to prevaccination sera, opsonization with the postvaccination sera reduced the survival inside macrophages ofS. Typhi but not ofS. Paratyphi A orS. Paratyphi B. Higher anti-S. Typhi O antigen (lipopolysaccharide [LPS]) IgG, but not IgA, antibody titers correlated significantly with postvaccination increases in opsonophagocytosis. No differences were observed between immunization with four doses of Ty21a or one dose of CVD 909. Ty21a and CVD 909 induced cross-reactive functional antibodies, predominantly againstS. Typhi. IgG anti-LPS antibodies may be important in phagocytic clearance of these organisms. Therefore, measurement of functional antibodies might be important in assessing the immunogenicity of a new generation of typhoid and paratyphoid A vaccines. (The CVD 909 study has been registered at ClinicalTrials.gov under registration no. NCT00326443.)

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