Antibody Responses after SARS-CoV-2 Vaccination in Lymphoma

Individuals with lymphoid malignancies have an increased mortality risk from COVID-19. Paradoxically, this population is least likely to be protected by SARS-CoV-2 vaccination as a result of disease- or treatment-related immunosuppression. Current data on vaccine responses in persons with lymphoid malignancies is limited. PROSECO is a UK multi-centre prospective observational study evaluating COVID-19 vaccine immune responses in individuals with lymphoma. This early interim analysis details the antibody responses to first- and second- SARS-CoV-2 vaccination with either BNT162b2 (Pfizer-BioNTech) and ChAdOx1 (AstraZeneca), in 129 participants. Responses are compared to those obtained in healthy volunteers. The key findings of this interim analysis are first, 61% of participants who are vaccinated during or within 6 months of receiving systemic anti-lymphoma treatment, do not have detectable antibodies despite two doses of vaccine. Second, individuals with curable disease such has Hodgkin (100%) and aggressive B-cell non-Hodgkin lymphoma (81%) develop robust antibody levels to either first or second doses, when vaccinated > 6 months after treatment completion. Third, participants incurable, indolent lymphomas have reduced antibody levels to first and second vaccine doses, irrespective of treatment history. Finally, whilst there was no difference in antibody responses between BNT162b2 and ChAdOx1 in lymphoma participants, BNT162b2 induces 11-fold higher antibody responses than ChAdOx1 after the second dose in healthy donors. These findings serve to reassure the community that individuals with treated Hodgkin and aggressive B-NHL can develop antibody responses to SARS-CoV-2 vaccine. Simultaneously it also highlights the critical need to identify an alternative strategy against COVID-19 for those undergoing systemic anti-lymphoma treatment, and for individuals with indolent lymphomas.

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Direct Comparison of Antibody Responses to Four SARS-CoV-2 Vaccines in Mongolia

10.1101/2021.08.22.21262161 ◽

2021 ◽

Author(s):

Naranjargal J. Dashdorj ◽

Oliver F. Wirz ◽

Katharina Roeltgen ◽

Emily Haraguchi ◽

Anthony S. Buzzanco ◽

...

Keyword(s):

Antibody Responses ◽

Health Interventions ◽

High Antibody ◽

Antibody Testing ◽

Public Health Interventions ◽

Vaccine Responses ◽

Blocking Activity ◽

Antibody Titers ◽

Alpha Variant ◽

Antibody Levels

Different vaccines for SARS-CoV-2 are approved in various countries, but few direct comparisons of the antibody responses they stimulate have been reported. We collected plasma specimens in July 2021 from 196 Mongolian participants fully vaccinated with one of four Covid vaccines: Pfizer/BioNTech, AstraZeneca, Sputnik V and Sinopharm. Functional antibody testing with a panel of nine SARS-CoV-2 viral variant RBD proteins reveal marked differences in the vaccine responses, with low antibody levels and RBD-ACE2 blocking activity stimulated by the Sinopharm and Sputnik V vaccines in comparison to the AstraZeneca or Pfizer/BioNTech vaccines. The Alpha variant caused 97% of infections in Mongolia in June and early July 2021. Individuals who recover from SARS-CoV-2 infection after vaccination achieve high antibody titers in most cases. These data suggest that public health interventions such as vaccine boosting, potentially with more potent vaccine types, may be needed to control the COVID-19 pandemic in Mongolia and worldwide.

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Durability of antibody response to vaccination and surrogate neutralization of emerging variants based on SARS-CoV-2 exposure history

Scientific Reports ◽

10.1038/s41598-021-96879-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Thomas W. McDade ◽

Alexis R. Demonbreun ◽

Amelia Sancilio ◽

Brian Mustanski ◽

Richard T. D’Aquila ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Messenger Rna ◽

Booster Vaccination ◽

Neutralizing Antibody ◽

Antibody Responses ◽

Post Vaccination ◽

Vaccine Responses ◽

Clinical Protection ◽

Exposure History ◽

Antibody Levels

AbstractTwo-dose messenger RNA vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are highly effective in preventing symptomatic COVID-19 infection. However, the durability of protection is not known, nor is the effectiveness against emerging viral variants. Additionally, vaccine responses may differ based on prior SARS-CoV-2 exposure history. To investigate protection against SARS-CoV-2 variants we measured binding and neutralizing antibody responses following both vaccine doses. We document significant declines in antibody levels three months post-vaccination, and reduced neutralization of emerging variants, highlighting the need to identify correlates of clinical protection to inform the timing of and indications for booster vaccination.

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Lenalidomide in non-Hodgkin lymphoma: biological perspectives and therapeutic opportunities

Blood ◽

10.1182/blood-2014-11-567792 ◽

2015 ◽

Vol 125 (16) ◽

pp. 2471-2476 ◽

Cited By ~ 33

Author(s):

Athena Kritharis ◽

Michael Coyle ◽

Jaya Sharma ◽

Andrew M. Evens

Keyword(s):

T Cell ◽

Immune Modulation ◽

Nk Cell ◽

Predictive Biomarkers ◽

Immune Synapse ◽

Antiproliferative Effects ◽

Lymphoid Malignancies ◽

Non Hodgkin Lymphoma ◽

Lymphoma Treatment ◽

Mantle Cell

AbstractLenalidomide is an immunomodulatory drug (IMiD) with activity in lymphoid malignancies occurring primarily through immune modulation (eg, T-cell immune synapse enhancement and NK-cell/T-cell effector augmentation) and antiproliferative effects. Food and Drug Administration–approved for bortezomib-resistant, relapsed/refractory mantle-cell lymphoma, lenalidomide has demonstrated efficacy in several additional lymphoma subtypes. There are many ongoing clinical trials examining the use of lenalidomide alone or in combinatorial therapy. It will be important in these studies to delineate reliable, predictive biomarkers to optimally integrate lenalidomide into lymphoma treatment paradigms.

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The metabolic hormone leptin promotes the function of TFH cells and supports vaccine responses

Nature Communications ◽

10.1038/s41467-021-23220-x ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Jun Deng ◽

Qian Chen ◽

Zhian Chen ◽

Kaili Liang ◽

Xin Gao ◽

...

Keyword(s):

Leptin Receptor ◽

Serum Levels ◽

Affinity Maturation ◽

Antibody Responses ◽

Vaccine Failure ◽

Vaccine Responses ◽

Follicular Helper ◽

B Virus ◽

And Function ◽

Metabolic Hormone

AbstractFollicular helper T (TFH) cells control antibody responses by supporting antibody affinity maturation and memory formation. Inadequate TFH function has been found in individuals with ineffective responses to vaccines, but the mechanism underlying TFH regulation in vaccination is not understood. Here, we report that lower serum levels of the metabolic hormone leptin associate with reduced vaccine responses to influenza or hepatitis B virus vaccines in healthy populations. Leptin promotes mouse and human TFH differentiation and IL-21 production via STAT3 and mTOR pathways. Leptin receptor deficiency impairs TFH generation and antibody responses in immunisation and infection. Similarly, leptin deficiency induced by fasting reduces influenza vaccination-mediated protection for the subsequent infection challenge, which is mostly rescued by leptin replacement. Our results identify leptin as a regulator of TFH cell differentiation and function and indicate low levels of leptin as a risk factor for vaccine failure.

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Low Immunogenicity of Intravesical Phage Therapy for Urogenitary Tract Infections

Antibiotics ◽

10.3390/antibiotics10060627 ◽

2021 ◽

Vol 10 (6) ◽

pp. 627

Author(s):

Sławomir Letkiewicz ◽

Marzanna Łusiak-Szelachowska ◽

Ryszard Międzybrodzki ◽

Maciej Żaczek ◽

Beata Weber-Dąbrowska ◽

...

Keyword(s):

Clinical Trial ◽

Bacterial Infections ◽

Phage Therapy ◽

Serum Antibody ◽

Multidrug Resistant ◽

Antibody Responses ◽

Urogenital Infections ◽

Reliable Model ◽

Tract Infections ◽

Antibody Levels

Patients with chronic urinary and urogenital multidrug resistant bacterial infections received phage therapy (PT) using intravesical or intravesical and intravaginal phage administration. A single course of PT did not induce significant serum antibody responses against administered phage. Whilst the second cycle of PT caused a significant increase in antibody levels, they nevertheless remained quite low. These data combined with good therapy results achieved in some patients suggest that this mode of PT may be an efficient means of therapy for urogenital infections and a reliable model for a clinical trial of PT.

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CD4+ CD25+ Regulatory T Cells Modulate the T-Cell and Antibody Responses in Helicobacter-Infected BALB/c Mice

Infection and Immunity ◽

10.1128/iai.01314-05 ◽

2006 ◽

Vol 74 (6) ◽

pp. 3519-3529 ◽

Cited By ~ 41

Author(s):

Maria Kaparakis ◽

Karen L. Laurie ◽

Odilia Wijburg ◽

John Pedersen ◽

Martin Pearse ◽

...

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Bacterial Colonization ◽

Antibody Responses ◽

T Helper 1 ◽

Time Of Infection ◽

Lymph Node Cells ◽

Antibody Levels ◽

And Control

ABSTRACT Gastric Helicobacter spp. induce chronic gastritis that may lead to ulceration and dysplasia. The host elicits a T helper 1 (Th1) response that is fundamental to the pathogenesis of these bacteria. We analyzed immune responses in Helicobacter-infected, normal mice depleted of CD4+ CD25+ T cells to investigate the in vivo role of regulatory T cells (Tregs) in the modulation of Helicobacter immunopathology. BALB/c and transgenic mice were depleted of CD4+ CD25+ T cells by administration of an anti-CD25 antibody either at the time of infection with Helicobacter or during chronic infection and gastritis. Depletion of CD25+ Tregs prior to and during infection of mice with Helicobacter spp. did not affect either bacterial colonization or severity of gastritis. Depletion of CD25+ Tregs was associated with increased Helicobacter-specific antibody levels and an altered isotype distribution. Paragastric lymph node cells from CD25+ Treg-depleted and control infected mice showed similar proliferation to Helicobacter antigens, but only cells from anti-CD25-treated animals secreted Th2 cytokines. CD25+ Tregs do not control the level of gastritis induced by gastric Helicobacter spp. in normal, thymus-intact BALB/c mice. However, CD25+ Tregs influence the cytokine and antibody responses induced by infection. Autoimmune gastritis is not induced in Helicobacter-infected mice depleted of CD25+ Tregs but is induced in CD25+ Treg-depleted mice, which have a higher frequency of autoreactive T cells.

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Determinants of Protection Against Measles Infection in a Vaccinated Healthcare Worker

Infection Control and Hospital Epidemiology ◽

10.1017/ice.2020.722 ◽

2020 ◽

Vol 41 (S1) ◽

pp. s185-s185

Author(s):

Annie St-Pierre ◽

Anne-Marie Charron ◽

Pamela Doyon-Plourde ◽

Caroline Quach

Keyword(s):

Vaccination Status ◽

Secondary Case ◽

Enzyme Linked Immunosorbent Assay ◽

Demographic Information ◽

Vaccine Response ◽

Vaccine Responses ◽

Equivocal Result ◽

Commercial Enzyme Immunoassay ◽

Antibody Levels ◽

Care Worker

Background: In 2019, a measles community outbreak resulted in a secondary case in a health care worker (HCW) working in a pediatric hospital in Montral, Canada. Following the event, HCWs were screened to identify individuals susceptible to measles infection based on serology results. Objective: Our aim was to assess measles seroprotection rates and to evaluate vaccine responses of susceptible HCWs using commercial enzyme immunoassay (EIA) or enzyme linked immunosorbent assay (ELISA). Methods: Emergency department (ED) employees, including doctors, were screened for measles susceptibility as part of a postoutbreak measure by the hospital occupational health service. Demographic information was collected. Measles history and vaccination information were collected using a personal vaccination booklet, employee vaccination profile, or the Qubec vaccination registry. According to the Quebec Immunization Protocol (PIQ), individuals born before 1970, or who have received 2 doses of a measles-containing vaccines are considered protected. Individuals with undetectable or equivocal antibody levels were considered at risk of measles infection. These individuals were offered vaccination and were tested for vaccine response 4 weeks after vaccination. Results: Anti-IgG measles antibody results, demographic information, and vaccination information were obtained for 257 employees. The results are currently available for 233 HCWs: 224 HCWs (96%) were seropositive, 7 (3%) were seronegative, and 2 were equivocal. Among seronegative individuals, 6 (85.7%) were born after 1980 and 3 (42.9%) had received 2 doses of a measles-containing vaccine. Of those with an equivocal result, 1 (50%) had received 2 doses and 1 (50%), born after 1970, did not confirm vaccination status. Finally, 9 (4%) of seropositive individuals were not vaccinated; of whom 8 (88.9%) were born before 1970. Conclusions: Our preliminary results suggest that the 95% immunity threshold that is usually required to prevent secondary transmission of measles has been reached in our ED HCW cohort. Even years after the second MMR dose, HCWs remain well protected. Relying on documented vaccination status is thus acceptable.Funding: NoneDisclosures: None

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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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Molecular characterization of Plasmodium falciparum PHISTb proteins as potential targets of naturally-acquired immunity against malaria

Wellcome Open Research ◽

10.12688/wellcomeopenres.15919.1 ◽

2020 ◽

Vol 5 ◽

pp. 136

Author(s):

Tony I. Isebe ◽

Joel L. Bargul ◽

Bonface M. Gichuki ◽

James M. Njunge ◽

James Tuju ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Malaria Transmission ◽

The Gambia ◽

Antibody Responses ◽

Transmission Intensity ◽

Parasite Development ◽

Natural Immunity ◽

Malaria Transmission Intensity ◽

Transmission Region ◽

Antibody Levels

Background: Plasmodium falciparum causes the deadliest form of malaria in humans. Upon infection, the host’s infected red blood cells (iRBCs) are remodelled by exported parasite proteins in order to provide a niche for parasite development and maturation. Methods: Here we analysed the role of three PHISTb proteins Pf3D7_0532400, Pf3D7_1401600, and Pf3D7_1102500 by expressing recombinant proteins and evaluated antibody responses against these proteins using immune sera from malaria-exposed individuals from Kenya and The Gambia in Africa. Results: Our findings show that children and adults from malaria-endemic regions recognized the three PHISTb proteins. Responses against the PHISTb proteins varied with malaria transmission intensity in three different geographical sites in Kenya (Siaya and Takaungu) and The Gambia (Sukuta). Antibody responses against PHISTb antigens Pf3D7_1102500 and Pf3D7_1401600 were higher in Sukuta, a low transmission region in the Gambia, as compared to Siaya, a high transmission region in western Kenya, unlike Pf3D7_0532400. Anti-PHIST responses show a negative correlation between antibody levels and malaria transmission intensity for two PHIST antigens, Pf3D7_1102500 and Pf3D7_1401600. However, we report a correlation in antibody responses between schizont extract and Pf3D7_0532400 (p=0.00582). Acquisition of anti-PHIST antibodies was correlated with exposure to malaria for PHISTb protein Pf3D7_0532400 (p=0.009) but not the other PHIST antigens Pf3D7_1102500 and Pf3D7_1401600 (p=0.507 and p=0.15, respectively, CI=95%). Children aged below 2 years had the lowest antibody levels, but the responses do not correlate with age differences. Conclusions: Collectively, these findings provide evidence of natural immunity against PHISTb antigens that varies with level of malaria exposure and underscore potential for these parasite antigens as possible serological markers to P. falciparum infection aimed at contributing to malaria control through vaccine development.

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Mucosal versus systemic antibody responses to SARS-CoV-2 antigens in COVID-19 patients

10.1101/2020.08.01.20166553 ◽

2020 ◽

Cited By ~ 10

Author(s):

Baweleta Isho ◽

Kento T Abe ◽

Michelle Zuo ◽

Alainna J Jamal ◽

Bhavisha Rathod ◽

...

Keyword(s):

Antibody Response ◽

Upper Airway ◽

Mucosal Immune Response ◽

Antibody Responses ◽

Igg Antibodies ◽

Blood Draw ◽

Neutralization Activity ◽

Surrogate Measure ◽

Antibody Levels ◽

Negative Controls

While the antibody response to SARS-CoV-2 has been extensively studied in blood, relatively little is known about the mucosal immune response and its relationship to systemic antibody levels. Since SARS-CoV-2 initially replicates in the upper airway, the antibody response in the oral cavity is likely an important parameter that influences the course of infection, but how it correlates to the antibody response in serum is not known. Here, we profile by enzyme linked immunosorbent assays (ELISAs) IgG, IgA and IgM responses to the SARS-CoV-2 spike protein (full length trimer) and its receptor binding domain (RBD) in serum (n=496) and saliva (n=90) of acute and convalescent patients with laboratory-diagnosed COVID-19 ranging from 3-115 days post-symptom onset (PSO), compared to negative controls. Anti-CoV-2 antibody responses were readily detected in serum and saliva, with peak IgG levels attained by 16-30 days PSO. Whereas anti-CoV-2 IgA and IgM antibodies rapidly decayed, IgG antibodies remained relatively stable up to 105 days PSO in both biofluids. In a surrogate neutralization ELISA (snELISA), neutralization activity peaks by 31-45 days PSO and slowly declines, though a clear drop is detected at the last blood draw (105-115 days PSO). Lastly, IgG, IgM and to a lesser extent IgA responses to spike and RBD in the serum positively correlated with matched saliva samples. This study confirms that systemic and mucosal humoral IgG antibodies are maintained in the majority of COVID-19 patients for at least 3 months PSO. Based on their correlation with each other, IgG responses in saliva may serve as a surrogate measure of systemic immunity.

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