scholarly journals Efficient mucosal antibody response to SARS-CoV-2 vaccination is induced in previously infected individuals

2021 ◽  
Author(s):  
Kaori Sano ◽  
Disha Bhavsar ◽  
Gagandeep Singh ◽  
Daniel Floda ◽  
Komal Srivastava ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Immune Responses ◽  
Mucosal Immunity ◽  
Respiratory Infections ◽  
Antibody Responses ◽  
Secretory Iga ◽  
Mucosal Antibody ◽  
Before And After ◽  
Paired Serum ◽  
Study Participants

AbstractMucosal immune responses are critical to prevent respiratory infections but it is unclear to what extent antigen specific mucosal secretory IgA (SIgA) antibodies are induced by mRNA vaccination in humans. We analyzed, therefore, paired serum and saliva samples from study participants with and without COVID-19 at multiple timepoints before and after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination. Our results suggest that the level of mucosal SIgA responses induced by mRNA vaccination depend on pre-existing immunity. Indeed, vaccination induced only a weak mucosal SIgA response in individuals without pre-existing mucosal antibody responses to SARS-CoV-2 while SIgA induction after vaccination was efficient in COVID-19 survivors. Our data indicate that vaccinated seropositive individuals were able to swiftly induce relatively high anti-spike SIgA responses by boosting pre-existing mucosal immunity. In contrast, seronegative individuals did not have pre-existing anti-SARS-CoV-2 or cross-reacting anti-HCoV SIgA antibodies prior to vaccination, and, thus, little or no anti-SARS-CoV-2 SIgA antibodies were induced by vaccination in these individuals.

scholarly journals Immune profiling reveals early disease trajectories associated with COVID-19 mortality: a sub-study from the ACTT-1 trial

2021 ◽  
Author(s):  
Joshua M Thiede ◽  
Abigail R Gress ◽  
Samuel D Libby ◽  
Christine E Ronayne ◽  
William E Matchett ◽  
...  
Keyword(s):  
Immune Responses ◽  
Antiviral Therapy ◽  
Symptom Onset ◽  
Antibody Responses ◽  
Early Disease ◽  
Host Immune Responses ◽  
Study Enrollment ◽  
Cytokine Responses ◽  
Study Participants ◽  
Immune Profiling

Abstract COVID-19 outcomes are linked to host immune responses and may be impacted by antiviral therapy. We investigated antibody and cytokine responses in ACTT-1 study participants enrolled at our center. We studied serum specimens from 19 hospitalized adults with COVID-19 randomized to treatment with remdesivir or placebo. We assessed SARS-CoV-2 antibody responses and identified cytokine signatures using hierarchical clustering. We identified no clear immunologic trends attributable to remdesivir treatment. Seven subjects were initially seronegative at study enrollment, and all four deaths occurred in this group with more recent symptom onset. We identified three dominant cytokine signatures, demonstrating different disease trajectories.

scholarly journals Pneumococcal colonization impairs nasal and lung mucosal immune responses to Live Attenuated Influenza Vaccination in adults

2020 ◽  
Author(s):  
Beatriz F. Carniel ◽  
Fernando Marcon ◽  
Jamie Rylance ◽  
Seher Zaidi ◽  
Jesus Reine ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Influenza Vaccination ◽  
Cellular Responses ◽  
Antibody Responses ◽  
Virus Infections ◽  
Mucosal Antibody ◽  
Pneumococcal Colonization ◽  
Differential Immunity ◽  
Nasal Microbiota

ABSTRACTInfluenza virus infections affect millions of people annually. Current available vaccines provide varying rates of protection. There is a knowledge gap on how the nasal microbiota, particularly established pneumococcal colonization, shapes the response to influenza vaccination. In this study, we inoculated healthy adults with live S. pneumoniae and vaccinated them three days later with either TIV or LAIV. Vaccine-induced immune responses were assessed in nose, blood and lung. Nasal pneumococcal colonization had no impact upon TIV-induced antibody responses to influenza, which manifested in all compartments. However, pre-existing pneumococcal colonization dampened LAIV-mediated mucosal antibody responses, primarily IgA in the nose and IgG in the lung. Pulmonary influenza-specific cellular responses were more apparent in the LAIV group compared to either TIV or an unvaccinated group. These results indicate that TIV and LAIV elicit differential immunity to adults and that LAIV immunogenicity is diminished by the nasal presence of S. pneumoniae. This important confounder should be considered when assessing LAIV efficacy.

scholarly journals Intranasal Immunization with a Colloid-Formulated Bacterial Extract Induces an Acute Inflammatory Response in the Lungs and Elicits Specific Immune Responses

2004 ◽  
Vol 72 (5) ◽  
pp. 2679-2688 ◽  
Author(s):  
A. Rial ◽  
D. Lens ◽  
L. Betancor ◽  
H. Benkiel ◽  
J. S. Silva ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Immune Responses ◽  
Respiratory Infections ◽  
Interleukin 10 ◽  
Secretory Iga ◽  
Acute Inflammatory Response ◽  
Necrosis Factor Alpha ◽  
Bacterial Extract ◽  
Ifn Γ ◽  
Tract Infections

ABSTRACT Nonspecific stimulation of lung defenses by repeated oral administration of immunomodulators, such as bacterial extracts, has shown potential for the prevention of respiratory tract infections. Here, we show that intranasal (i.n.) immunization with a bacterial extract formulated as a colloid induces an acute inflammatory response in the lungs characterized by increased production of CCL and CXCL chemokines and a major influx of dendritic cells (DCs) and neutrophils, with a higher proportion of DCs showing an activated phenotype (high CD80/CD86 expression). Cytokine levels measured in bronchoalveolar-lavage samples showed a small increase in the production of tumor necrosis factor alpha and similar levels of the other cytokines measured (interleukin 10 [IL-10], IL-12, and gamma interferon [IFN-γ]) in immunized mice compared with control mice. However, the recall response of primed animals after antigenic challenge induced increased expression of IL-12 and IFN-γ mRNAs in lung homogenates. Overall, all these effects were not due to the lipopolysaccharide content in the bacterial extract. Furthermore, we found that three i.n. doses administered 2 to 3 weeks apart were enough to elicit long-lasting specific serum immunoglobulin G (IgG) and secretory IgA antibody responses. Assessment of IgG subclasses showed a balanced pattern of IgG1-IgG2a responses. The serum total IgE concentrations were also elevated in immunized mice 2 weeks after the third dose, but they significantly decreased soon afterwards. Our results suggest that simple formulations of bacterial extracts administered i.n. are highly immunogenic, eliciting local and systemic immune responses, and may serve as the basis for cost-effective immunotherapies for the prevention and treatment of respiratory infections.

scholarly journals SARS-CoV-2 vaccination induces neutralizing antibodies against pandemic and pre-emergent SARS-related coronaviruses in monkeys

2021 ◽  
Author(s):  
Kevin O. Saunders ◽  
Esther Lee ◽  
Robert Parks ◽  
David R. Martinez ◽  
Dapeng Li ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Geometric Mean ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Receptor Binding Domain ◽  
Neutralization Titer ◽  
The Uk ◽  
Further Development

SUMMARYBetacoronaviruses (betaCoVs) caused the severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) outbreaks, and now the SARS-CoV-2 pandemic. Vaccines that elicit protective immune responses against SARS-CoV-2 and betaCoVs circulating in animals have the potential to prevent future betaCoV pandemics. Here, we show that immunization of macaques with a multimeric SARS-CoV-2 receptor binding domain (RBD) nanoparticle adjuvanted with 3M-052-Alum elicited cross-neutralizing antibody responses against SARS-CoV-1, SARS-CoV-2, batCoVs and the UK B.1.1.7 SARS-CoV-2 mutant virus. Nanoparticle vaccination resulted in a SARS-CoV-2 reciprocal geometric mean neutralization titer of 47,216, and robust protection against SARS-CoV-2 in macaque upper and lower respiratory tracts. Importantly, nucleoside-modified mRNA encoding a stabilized transmembrane spike or monomeric RBD protein also induced SARS-CoV-1 and batCoV cross-neutralizing antibodies, albeit at lower titers. These results demonstrate current mRNA vaccines may provide some protection from future zoonotic betaCoV outbreaks, and provide a platform for further development of pan-betaCoV nanoparticle vaccines.

scholarly journals Enhanced Mucosal Immune Responses to HIV Virus-Like Particles Containing a Membrane-Anchored Adjuvant

mBio ◽  
2011 ◽  
Vol 2 (1) ◽  
Author(s):  
Elena V. Vassilieva ◽  
Bao-Zhong Wang ◽  
Andrei N. Vzorov ◽  
Li Wang ◽  
Ying-Chun Wang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Mucosal Immunity ◽  
Vaccine Development ◽  
Transmitted Disease ◽  
Hiv Vaccine ◽  
Antibody Responses ◽  
Significant Drop ◽  
Virus Like Particles ◽  
Hiv Virus ◽  
Mucosal Immune Responses

ABSTRACTPreviously, a modified HIV Env protein with a heterologous membrane anchor was found to be incorporated into HIV virus-like particles (VLPs) at 10-fold-higher levels than those of unmodified Env. To further improve the immunogenicity of such VLPs, membrane-anchored forms of bacterial flagellin (FliC) or a flagellin with a truncated variable region (tFliC) were constructed to be incorporated into the VLPs as adjuvants. HIV-specific immune responses induced by the resulting VLPs were determined in a guinea pig model. The VLPs induce enhanced systemic antibody responses by either systemic or mucosal vaccination and enhanced mucosal immunity by a mucosal immunization route, as demonstrated by high levels of HIV-specific serum IgG and mucosal IgG and IgA. The quality of the antibody responses was also improved, as shown by enhanced neutralization capacity. VLPs incorporating FliC were more effective in inducing systemic responses, while VLPs containing tFliC were more effective in inducing mucosal IgA responses. The IgG titers in sera were found to last for at least 5 months without a significant drop. These results indicate that HIV VLPs incorporating high levels of Env and a molecular adjuvant have excellent potential for further development as a prophylactic HIV vaccine.IMPORTANCEA prophylactic vaccine is urgently needed to control the spread of HIV/AIDS. Antigens inducing strong systemic and mucosal immune responses are promising as vaccines for this mucosally transmitted disease. We found that novel HIV virus-like particles (VLPs) presenting a high level of Env in its native membrane-bound form and coincorporating an innate immune-signaling adjuvant in the same particles were effective in inducing enhanced systemic and mucosal immunity. As new HIV vaccine candidates, these VLPs bridge the gaps of the innate and adaptive, as well as systemic and mucosal, immune responses, providing a new approach for HIV vaccine development.

scholarly journals Type IVB Pilus Operon Promoter Controlling Expression of the Severe Acute Respiratory Syndrome-Associated Coronavirus Nucleocapsid Gene in Salmonella enterica Serovar Typhi Elicits Full Immune Response by Intranasal Vaccination

2007 ◽  
Vol 14 (8) ◽  
pp. 990-997 ◽  
Author(s):  
Fengling Luo ◽  
Yong Feng ◽  
Min Liu ◽  
Pingfei Li ◽  
Qin Pan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Severe Acute Respiratory Syndrome ◽  
Immune Responses ◽  
Salmonella Enterica ◽  
Oral Delivery ◽  
Secretory Iga ◽  
N Gene ◽  
Foreign Gene ◽  
Th1 Cell ◽  
Vector Vaccine

ABSTRACT Attenuated Salmonella enterica serovar Typhi strains have been considered to be attractive as potential live oral delivery vector vaccines because of their ability to elicit the full array of immune responses in humans. In this study, we constructed an attenuated S. enterica serovar Typhi strain stably expressing conserved nucleocapsid (N) protein of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) by integrating the N gene into the pilV gene, which was under the control of the type IVB pilus operon promoter in S. enterica serovar Typhi. BALB/c mice were immunized with this recombinant strain through different routes: intranasally, orogastrically, intraperitoneally, and intravenously. Results showed that the intranasal route caused the highest production of specific immunoglobulin G (IgG), IgG2a, and secretory IgA, where IgG2a was imprinted as a Th1 cell bias. Moreover, this recombinant live vaccine induced significantly high levels of specific cytotoxic T-lymphocyte activities and increased gamma interferon-producing T cells compared with the parental strain. Our work provides insights into how the type IVB pilus operon promoter controlling SARS-CoV N gene expression in Salmonella might be attractive for a live-vector vaccine against SRAS-CoV infection, for it could induce mucosal, humoral, and cellular immune responses. Our work also indicates that the type IVB pilus operon promoter controlling foreign gene expression in Salmonella can elicit full immune responses by intranasal vaccination.

scholarly journals Anti-severe acute respiratory syndrome coronavirus-2 antibody responses following Pfizer-BioNTech vaccination in a patient with multiple sclerosis treated with ocrelizumab: a case report

2021 ◽  
Vol 49 (9) ◽  
pp. 030006052110443
Author(s):  
Hubert Mado ◽  
Katarzyna Kubicka-Bączyk ◽  
Monika Adamczyk-Sowa
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
Case Report ◽  
Severe Acute Respiratory Syndrome ◽  
Immune Responses ◽  
B Lymphocyte ◽  
Neurological Society ◽  
Antibody Responses ◽  
Post Vaccination ◽  
Lymphocyte Depletion

Patients with multiple sclerosis (MS) repeatedly receive therapies that cause B-lymphocyte depletion. This may lead to abnormal immune responses following coronavirus disease 2019 (COVID-19) vaccination, as has been suggested previously. We therefore evaluated post-vaccination immune responses in a patient with MS treated with ocrelizumab. The intervals between ocrelizumab infusions and vaccination were as recommended by the Section of Multiple Sclerosis and Neuroimmunology of the Polish Neurological Society. A reactive immune response was observed in this patient following vaccination. This suggests that appropriate intervals between ocrelizumab infusions and COVID-19 vaccinations may permit the generation of efficacious immune responses in patients receiving B-lymphocyte depleting therapies.

scholarly journals Pegylated Interferon-Alfa Suppresses Clonal Hematopoiesis in Polycythemia Vera and Essential Thrombocythemia and Is Associated with Immune Responses to Tumor Antigens

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1691-1691
Author(s):  
Tsewang Tashi ◽  
Tim Luetkens ◽  
Stephanie Avila ◽  
Soo Jin Kim ◽  
Josef T. Prchal
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Interferon Therapy ◽  
Tumor Antigens ◽  
Response Rate ◽  
Pegylated Interferon ◽  
Antibody Responses ◽  
Molecular Response ◽  
Before And After ◽  
Allelic Burden

Hydroxyurea is usually the first line treatment for high-risk polycythemia vera (PV) and essential thrombocythemia (ET), but interferon is an equally effective treatment. However, unlike hydroxyurea, several studies have shown higher rate of molecular response with pegylated interferon-alpha (PegINFa) and tolerable toxicity. We had reported earlier that in some female patients, polyclonal hematopoiesis is restored (Liu E et al, Blood, 2003) after interferon therapy. However, the mechanism of action of interferon on rescue of normal dormant hematopoiesis in PV and ET is not fully understood. Presence of immune response against PV & ET clone is long speculated and we had previously screened human testis cDNA library in plasma from a PV subject who converted to polyclonal hematopoiesis after interferon therapy, where presence of immune response were noted. We analyzed 48 patients diagnosed with PV and ET per WHO 2012 criteria who were treated with PegINFa at our institution. The majority of patients receiving PegINFa - 28 (58%) were second-line treatments after receiving hydroxyurea. The overall hematological response rate for PegINFa treated patients was 46 (95.8%), but 14 (29%) had to discontinue due to various toxicities. Of the 48 patients, 31 had evaluable JAK2V617F allelic burden at least at 2 time points, and the overall molecular response rate was 45% (14 of 31) with a median time of 24 months. In 4 (12.9%) patients, JAK2V617F allelic burden decreased to <1% after PegINFa treatment, with a median time of 29.5 months; however, no patients achieved complete molecular remission when examined by sensitive quantitative assay (Nussenzveig RH et al, Exp Hematol 2007) and also by digital PCR. In this pilot study, using plasma samples from 7 PV patients collected before and after treatment with PegINFa, we screened for antibody responses to a panel of 16 commercially available and 11 custom generated recombinant tumor-associated antigens (TAA) by enzyme-linked immunosorbent assay (ELISA) as previously described (Luetkens T et al., Leukemia Research 2010). In brief, we coated 96-well MaxiSorp (Nunc) plates over night at 4°C with 5mg/ml recombinant protein, blocked plates in 4% non-fat milk PBS (M-PBS) and incubated antigens with patient sera diluted 1:100 in M-PBS for 2h at room temperature. Bound antibodies were detected using a secondary anti-human immunoglobulin G antibody linked to alkaline phosphatase (Southern Biotech) followed by development with p-nitrophenyl phosphate. In patients #1, #2 and #3, who showed a decrease in JAK2V617F allelic burden after PegINFa treatment, we observed antibody responses against antigens MAGEB1, MAGEH1, MAGEA1, and DKK1 before and after PegINFa treatment. In patients #4, #5 and #7, JAK2V617F allelic burden increased after PegINFa treatment, and we did not detect substantial immune responses against any antigens in our panel. In patient #6, no immune response was seen against any antigen on the panel even though there was a decrease in JAK2V617F allele burden. These preliminary data suggest that PegINFa can induce deep molecular responses in a subset of PV and ET patients, and is associated with presence of immune responses against tumor antigens. We speculate that PegINFa may augment the efficacy of pre-existing TAA-specific immune responses against PV and ET clone. We are in the process of validating these findings in a larger cohort of PV and ET patients treated with PegINFa. Disclosures No relevant conflicts of interest to declare.

scholarly journals Salivary anti-SARS-CoV-2 IgA as an accessible biomarker of mucosal immunity against COVID-19.

2020 ◽  
Author(s):  
Atul Varadhachary ◽  
Dev Chatterjee ◽  
Javier Garza ◽  
Robert Patrick Garr ◽  
Christopher Foley ◽  
...  
Keyword(s):  
Immune Responses ◽  
Disease Severity ◽  
Mucosal Immunity ◽  
Serum Antibody ◽  
Quantitative Measure ◽  
Secretory Iga ◽  
Respiratory Pathogens ◽  
Predictive Values ◽  
Salivary Iga ◽  
Mucosal Immune Responses

Background: Mucosal immunity, including secretory IgA (sIgA), plays an important role in early defenses against respiratory pathogens. Salivary testing, the most convenient way to measure sIgA, has been used to characterize mucosal immune responses to many viral infections including SARS, MERS, influenza, HIV, and RSV. However, its role has not yet been characterized in the COVID-19 pandemic. Here, we report development and validation of a rapid immunoassay for measuring salivary IgA against the SARS-CoV-2 virus, and report quantitative results in both pre-COVID-19 and muco-converted subjects. Methods: We developed and refined a specific test for salivary IgA against SARS-CoV-2 on the Brevitest platform, a rapid immunoassay system designed for point-of-care use. A qualitative test was validated as per FDA guidelines with saliva obtained from subjects prior to the emergence of COVID-19, and from PCR-confirmed COVID-19 patients. We also generated a quantitative measure of anti-SARS-CoV-2 salivary IgA. Time taken for saliva self-collection was measured and its ease-of-use assessed. Results: We successfully validated a qualitative salivary assay for SARS-CoV-2 IgA antibodies, with positive and negative predictive values of 92% and 97%, respectively, and no observable cross-reactivity with any of seven potential confounders. Pre-COVID-19 saliva samples showed an 8-fold range of IgA concentrations, suggesting a broad continuum of natural antibody resistance against the novel virus, though at levels lower than that observed in COVID-19 PCR-confirmed subjects. Samples from muco-positive subjects also shown a ~9-fold variation in salivary IgA levels, with elevated salivary IgA observed beyond three months after onset of symptoms. We observed a correlation (r=0.4405) between salivary IgA levels and COVID-19 disease severity. In anecdotal observations, we observed individuals who exhibited antibodies early in the course of their disease, contemporaneously with a positive PCR test, as well as individuals who muco-converted despite no known direct exposure to a COVID-19 patient, no symptoms, and negative molecular and/or serum antibody tests. Salivary collection took 5-10 minutes, and was reported as being easy (mean of 1.1 on a scale of 1 to 10). Implications: Mucosal immunity, including secretory IgA, plays an important role in host defense against respiratory pathogens, and our early data suggest it may do so in COVID-19. Salivary IgA, an accessible marker of mucosal immunity, may be a useful indicator of several key parameters including individual and community immune response, disease severity, clinical risk, and herd immunity. The non-invasive nature and ease of saliva collection facilitates its potential use as a biomarker for ongoing patient assessment and management, as well as a community surveillance tool. By measuring mucosal immune responses directly and systemic immune responses indirectly, salivary IgA could be useful in developing and deploying a vaccine(s) against COVID-19. Quantitative IgA assessment could also potentially serve as a tool to segment the population into different risk categories and inform individual and collective decisions relating to appropriate activities and vaccine prioritization/delivery. These data reinforce the importance of further investigation into the role of mucosal immunity and IgA in host responses against COVID-19.

Oral Immune Activation by Disgust and Disease-Related Pictures

2015 ◽  
Vol 29 (3) ◽  
pp. 119-129 ◽  
Author(s):  
Richard J. Stevenson ◽  
Deborah Hodgson ◽  
Megan J. Oaten ◽  
Luba Sominsky ◽  
Mehmet Mahmut ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Innate Immune Response ◽  
Negative Control ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Immune Markers ◽  
Before And After ◽  
Secondary Analyses ◽  
Image Set

Abstract. Both disgust and disease-related images appear able to induce an innate immune response but it is unclear whether these effects are independent or rely upon a common shared factor (e.g., disgust or disease-related cognitions). In this study we directly compared these two inductions using specifically generated sets of images. One set was disease-related but evoked little disgust, while the other set was disgust evoking but with less disease-relatedness. These two image sets were then compared to a third set, a negative control condition. Using a wholly within-subject design, participants viewed one image set per week, and provided saliva samples, before and after each viewing occasion, which were later analyzed for innate immune markers. We found that both the disease related and disgust images, relative to the negative control images, were not able to generate an innate immune response. However, secondary analyses revealed innate immune responses in participants with greater propensity to feel disgust following exposure to disease-related and disgusting images. These findings suggest that disgust images relatively free of disease-related themes, and disease-related images relatively free of disgust may be suboptimal cues for generating an innate immune response. Not only may this explain why disgust propensity mediates these effects, it may also imply a common pathway.

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