scholarly journals Longitudinal immune dynamics of mild COVID-19 define signatures of recovery and persistence

2021 ◽  
Author(s):  
Aarthi Talla ◽  
Suhas V Vasaikar ◽  
Maria P Lemos ◽  
Zoe Moodie ◽  
Mark-Phillip Lee Pebworth ◽  
...  
Keyword(s):  
Immune Responses ◽  
Acute Infection ◽  
Early Time ◽  
Chromatin Accessibility ◽  
Outpatient Setting ◽  
Correlated Data ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Serum Proteomics ◽  
Humoral Responses

SARS-CoV-2 has infected over 160 million and caused more than 3 million deaths to date. Most individuals (>80%) have mild symptoms and recover in the outpatient setting, but detailed studies of immune responses have focused primarily on moderate to severe COVID-19. We deeply profiled the longitudinal immune response in individuals with mild COVID beginning with early time points post-infection (1-15 days) and proceeding through convalescence to >100 days after symptom onset. We correlated data from single cell analyses of peripheral blood cells, serum proteomics, virus-specific cellular and humoral immune responses, and clinical metadata. Acute infection was characterized by vigorous coordinated innate and adaptive activation, including an early cellular and proteomic signature that correlated with the amplitude of virus-specific humoral responses after day 30. We characterized signals associated with recovery and convalescence to define a new signature of inflammatory cytokines, gene expression, and chromatin accessibility that persists in individuals with post-acute sequelae of SARS-CoV-2 infection (PASC).

scholarly journals Autoantibodies in COVID-19 correlate with anti-viral humoral responses and distinct immune signatures

2022 ◽  
Author(s):  
Patrick Taeschler ◽  
Carlo Cervia ◽  
Yves Zurbuchen ◽  
Sara Hasler ◽  
Christian Pou ◽  
...  
Keyword(s):  
Indirect Immunofluorescence ◽  
Autoantibody Production ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Serum Proteomics ◽  
Immune Signatures ◽  
Autoimmune Pathology ◽  
Highly Sensitive ◽  
One Year ◽  
Humoral Responses

Background: Several autoimmune features occur during coronavirus disease 2019 (COVID-19), with possible implications for disease course, immunity, and autoimmune pathology. Objective: We longitudinally screened for clinically relevant systemic autoantibodies to assess their prevalence, temporal trajectory, and association with immunity, comorbidities, and severity of COVID-19. Methods: We performed highly sensitive indirect immunofluorescence assays to detect anti-nuclear antibodies (ANA) and anti-neutrophil cytoplasmic antibodies (ANCA), along with serum proteomics and virome-wide serological profiling in a multicentric cohort of 175 COVID-19 patients followed-up to one year after infection, eleven vaccinated individuals, and 41 unexposed controls. Results: Compared to healthy controls, similar prevalence and patterns of ANA were present in patients during acute COVID-19 and recovery. However, paired analysis revealed a subgroup of patients with transient presence of certain ANA patterns during acute COVID-19. Furthermore, patients with severe COVID-19 exhibited a high prevalence of ANCA during acute disease. These autoantibodies were quantitatively associated with higher SARS-CoV-2-specific antibody titers in COVID-19 patients and in vaccinated individuals, thus linking autoantibody production to increased antigen-specific humoral responses. Notably, the qualitative breadth of antibodies cross-reactive with other coronaviruses was comparable in ANA-positive and ANA-negative individuals during acute COVID-19. In autoantibody-positive patients, multiparametric characterization demonstrated an inflammatory signature during acute COVID-19 and alterations of the B cell compartment after recovery. Conclusion: Highly sensitive indirect immunofluorescence assays revealed transient autoantibody production during acute SARS-CoV-2 infection, while the presence of autoantibodies in COVID-19 patients correlated with increased anti-viral humoral immune responses and inflammatory immune signatures.

scholarly journals Overcoming Immunity to a Viral Vaccine by DNA Priming before Vector Boosting

2003 ◽  
Vol 77 (1) ◽  
pp. 799-803 ◽  
Author(s):  
Zhi-yong Yang ◽  
Linda S. Wyatt ◽  
Wing-pui Kong ◽  
Zoe Moodie ◽  
Bernard Moss ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Vectors ◽  
Ebola Virus ◽  
Viral Vector ◽  
Hemorrhagic Fever ◽  
Viral Immunity ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Viral Vaccine ◽  
Humoral Responses

ABSTRACT Replication-defective adenovirus (ADV) and poxvirus vectors have shown potential as vaccines for pathogens such as Ebola or human immunodeficiency virus in nonhuman primates, but prior immunity to the viral vector in humans may limit their clinical efficacy. To overcome this limitation, the effect of prior viral exposure on immune responses to Ebola virus glycoprotein (GP), shown previously to protect against lethal hemorrhagic fever in animals, was studied. Prior exposure to ADV substantially reduced the cellular and humoral immune responses to GP expressed by ADV, while exposure to vaccinia inhibited vaccine-induced cellular but not humoral responses to GP expressed by vaccinia. This inhibition was largely overcome by priming with a DNA expression vector before boosting with the viral vector. Though heterologous viral vectors for priming and boosting can also overcome this effect, the paucity of such clinical viral vectors may limit their use. In summary, it is possible to counteract prior viral immunity by priming with a nonviral, DNA vaccine.

Pathogenic and humoral immune responses to porcine reproductive and respiratory syndrome virus (PRRSV) are related to viral load in acute infection

2004 ◽  
Vol 102 (3) ◽  
pp. 233-247 ◽  
Author(s):  
Wesley Johnson ◽  
Michael Roof ◽  
Eric Vaughn ◽  
Jane Christopher-Hennings ◽  
Craig R. Johnson ◽  
...  
Keyword(s):  
Viral Load ◽  
Immune Responses ◽  
Acute Infection ◽  
Respiratory Syndrome Virus ◽  
Humoral Immune ◽  
Humoral Immune Responses

scholarly journals Humoral Immune Responses against the Mycobacteriumtuberculosis 38-Kilodalton, MTB48, and CFP-10/ESAT-6 Antigens in Tuberculosis

2010 ◽  
Vol 17 (3) ◽  
pp. 372-375 ◽  
Author(s):  
Xueqiong Wu ◽  
Yourong Yang ◽  
Junxian Zhang ◽  
Bangying Li ◽  
Yan Liang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Healthy Subjects ◽  
Enzyme Linked Immunosorbent Assay ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Single Antigen ◽  
Human Sera ◽  
Low Sensitivity ◽  
Humoral Responses ◽  
Culture Negative

ABSTRACT The diagnosis of smear-negative and culture-negative patients with active tuberculosis (TB) is challenging. The detection of Mycobacterium tuberculosis-specific antibodies in human sera has been an important diagnostic aid. However, detection of antibody responses to a single antigen usually has a low sensitivity for diagnosis of TB. In this study, humoral immune responses against recombinant M. tuberculosis 38-kDa, MTB48, and CFP-10/ESAT-6 (culture filtrate protein 10/6-kDa early secreted antigen target of M. tuberculosis) antigens in 250 Chinese TB patients and 260 healthy subjects were evaluated by an enzyme-linked immunosorbent assay (ELISA). The levels of antibodies against those antigens in TB patients, even in bacterium-negative ones, were significantly higher than those in healthy subjects (P < 0.001). The serodiagnostic sensitivities to detect antibodies against individual antigens, i.e., recombinant M. tuberculosis 38-kDa, MTB48, and CFP-10/ESAT-6 antigens, in TB patients were 73.6%, 73.2%, and 60.4%, respectively, with specificities of 85.4%, 77.7%, and 73.8%, respectively. Importantly, the sensitivity to positively detect humoral responses to one of the antigens increased further. Our data suggest that the humoral immune responses to M. tuberculosis antigens in TB patients are heterogeneous. The 38-kDa, MTB48, and CFP-10/ESAT-6 antigens can be used as the cocktail antigens in the serodiagnosis of active TB, especially for smear- or culture-negative TB cases.

scholarly journals Asymptomatic or mild symptomatic SARS-CoV-2 infection elicits durable neutralizing antibody responses in children and adolescents

2021 ◽  
Author(s):  
Carolina Garrido ◽  
Jillian H Hurst ◽  
Cynthia G. Lorang ◽  
Jhoanna N. Aquino ◽  
Javier Rodriguez ◽  
...  
Keyword(s):  
Immune Responses ◽  
Children And Adolescents ◽  
Acute Infection ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Symptomatic Infection ◽  
Neutralizing Activity ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Broad Array

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.

scholarly journals Strong humoral immune responses against SARS-CoV-2 Spike after BNT162b2 mRNA vaccination with a sixteen-week interval between doses

2021 ◽  
Author(s):  
Alexandra Tauzin ◽  
Shang Yu Gong ◽  
Guillaume Beaudoin-Bussieres ◽  
Dani Vezina ◽  
Romain Gasser ◽  
...  
Keyword(s):  
Public Health ◽  
Immune Responses ◽  
Vaccine Efficacy ◽  
Standard Regimen ◽  
Effector Functions ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Health Authorities ◽  
Public Health Authorities ◽  
Humoral Responses

While the standard regimen of the BNT162b2 mRNA vaccine includes two doses administered three weeks apart, some public health authorities decided to space them, raising concerns about vaccine efficacy. Here, we analyzed longitudinal humoral responses including antibody binding, Fc-mediated effector functions and neutralizing activity against the D614G strain but also variants of concern and SARS-CoV-1 in a cohort of SARS-CoV-2 naive and previously infected individuals, with an interval of sixteen weeks between the two doses. While the administration of a second dose to previously infected individuals did not significantly improve humoral responses, we observed a significant increase of humoral responses in naive individuals after the 16-weeks delayed second shot, achieving similar levels as in previously infected individuals. Our results highlight strong vaccine-elicited humoral responses with an extended interval BNT162b2 vaccination for naive individuals.

Optimization of Expression and Purification of Recombinant Mouse plac1

2022 ◽  
Author(s):  
Shaghayegh Rahdan ◽  
Seyed Alireza Razavi ◽  
Mahboobeh Nazari ◽  
Sorour Shojaeian ◽  
Fazel Shokri ◽  
...  
Keyword(s):  
Immune Responses ◽  
Recombinant Proteins ◽  
Culture Medium ◽  
Ectopic Expression ◽  
Expression And Purification ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Wide Range ◽  
Humoral Responses ◽  
And Control

Background: Placenta-specific 1 (PLAC1) is one of the recently-discovered Cancer-Testis-Placenta (CTP) antigen with restricted normal tissue and ectopic expression in a wide range of cancer cells from different histological origins. The production of recombinant human PLAC1 has already been optimized; however, no study has been reported so far on the production and purification of mouse plac1. In this study, mouse plac1 expression and purification was optimized in a prokaryotic system and the effects of the generated proteins on inducing humoral responses in mice were investigated. Methods: A fusion protein containing full extracellular domain of mouse plac1, immunostimulatory peptides, tetanus toxin P2P30 and PADRE and KDEL3 signal (main plac1), and the same fragment without immunostimulatory peptides (control plac1) was produced. To optimize production and purification steps, different parameters including bacterial strain, cultivation temperature, cultivation time, IPTG concentration, culture medium, and also different buffers for purification of the recombinant proteins were tested. After confirming the identity of recombinant plac1 proteins with Western Blotting (WB) and ELISA assays, these proteins were subcutaneously injected in mice with Freund's adjuvant and the anti-plac1 antibody response was detected by ELISA. Results: The optimal expression level of main and control plac1 was obtained in BL21 (DE3) and TB culture medium in the presence of 0.25 mM IPTG after 24 hr of induction at 15°C. The buffer containing 2% sarkosyl produced higher yield and purity. Our results showed specific reactivity of anti-human recombinant plac1 polyclonal antibody with both main and control plac1 recombinant proteins in WB and ELISA analysis. Both proteins induced humoral responses in mice; however, anti-plac1  antibody titer was significantly higher in sera of mice immunized with main compared to control plac1. Conclusion: In this study, an optimized protocol for production and purification of mouse plac1 was reported and it was shown that insertion of immunostimulatory peptides in gene construct could efficiently enhance humoral immune responses against mouse plac1, which could potentially augment cellular immune responses against plac1 leading to more effective anti-cancer responses.

scholarly journals Humoral Immune Responses of Tuberculosis Patients in Brazil Indicate Recognition of Mycobacterium tuberculosis MPT-51 and GlcB

2008 ◽  
Vol 15 (3) ◽  
pp. 579-581 ◽  
Author(s):  
Cristina Melo Cardoso Almeida ◽  
Arioldo C. Vasconcelos ◽  
André Kipnis ◽  
Ana Lúcia Andrade ◽  
Ana Paula Junqueira-Kipnis
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Immunosorbent Assay ◽  
Immunoglobulin M ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tuberculosis Patients ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Humoral Responses

ABSTRACT The humoral responses to recombinant MPT-51 and GlcB was determined by using an enzyme-linked immunosorbent assay. Levels of immunoglobulin M (IgM) against MPT-51 and IgG against GlcB were higher among tuberculosis (TB) patients than among control individuals. When the MPT-51 and GlcB assays were combined, 90.8% specificity and 75.5% sensitivity were observed. MPT-51 and GlcB were recognized in the humoral responses of Brazilian TB patients.

scholarly journals Humoral Responses and Serological Assays in SARS-CoV-2 Infections

2020 ◽  
Vol 11 ◽  
Author(s):  
Yannick Galipeau ◽  
Matthew Greig ◽  
George Liu ◽  
Matt Driedger ◽  
Marc-André Langlois
Keyword(s):  
Immune Responses ◽  
Vaccine Development ◽  
Cross Reactivity ◽  
The Novel ◽  
Epidemiological Models ◽  
Humoral Immune ◽  
Health Measures ◽  
Humoral Immune Responses ◽  
Humoral Responses ◽  
Vaccination Campaigns

In December 2019, the novel betacoronavirus Severe Acute Respiratory Disease Coronavirus 2 (SARS-CoV-2) was first detected in Wuhan, China. SARS-CoV-2 has since become a pandemic virus resulting in hundreds of thousands of deaths and deep socioeconomic implications worldwide. In recent months, efforts have been directed towards detecting, tracking, and better understanding human humoral responses to SARS-CoV-2 infection. It has become critical to develop robust and reliable serological assays to characterize the abundance, neutralization efficiency, and duration of antibodies in virus-exposed individuals. Here we review the latest knowledge on humoral immune responses to SARS-CoV-2 infection, along with the benefits and limitations of currently available commercial and laboratory-based serological assays. We also highlight important serological considerations, such as antibody expression levels, stability and neutralization dynamics, as well as cross-reactivity and possible immunological back-boosting by seasonal coronaviruses. The ability to accurately detect, measure and characterize the various antibodies specific to SARS-CoV-2 is necessary for vaccine development, manage risk and exposure for healthcare and at-risk workers, and for monitoring reinfections with genetic variants and new strains of the virus. Having a thorough understanding of the benefits and cautions of standardized serological testing at a community level remains critically important in the design and implementation of future vaccination campaigns, epidemiological models of immunity, and public health measures that rely heavily on up-to-date knowledge of transmission dynamics.

scholarly journals Antibodies from rabbits immunized with HIV-1 clade B SOSIP trimers can neutralize multiple clade B viruses by destabilizing the envelope glycoprotein

2021 ◽  
Author(s):  
M. M. van Haaren ◽  
L. E. McCoy ◽  
J. L. Torres ◽  
W Lee ◽  
C. A. Cottrell ◽  
...  
Keyword(s):  
Immune Responses ◽  
Envelope Glycoprotein ◽  
Neutralizing Antibodies ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Immunization Strategies ◽  
Clade B ◽  
Humoral Responses ◽  
Neutralization Ability ◽  
Hiv 1

The high HIV-1 viral diversity is a formidable hurdle for the development of an HIV-1 vaccine. Elicitation of broadly neutralizing antibodies (bNAbs) would offer a solution, but so far immunization strategies have failed to elicit bNAbs efficiently. To overcome the obstacles, it is important to understand the immune responses elicited by current HIV-1 envelope glycoprotein (Env) immunogens. To gain more insight, we characterized monoclonal antibodies (mAbs) isolated from rabbits immunized with Env SOSIP trimers based on the clade B isolate AMC008. Four rabbits that were immunized three times with AMC008 trimer developed robust autologous and sporadic low-titer heterologous neutralizing responses. Seventeen AMC008 trimer-reactive mAbs were isolated using antigen-specific single B cell sorting. Four of these mAbs neutralized the autologous AMC008 virus and several other clade B viruses. When visualized by electron microscopy, the complex of the neutralizing mAbs with the AMC008 trimer showed binding to the gp41 subunit with unusual approach angles and we observed that their neutralization ability depended on their capacity to induce Env trimer dissociation. Thus, AMC008 SOSIP trimer immunization induced clade B neutralizing mAbs with unusual approach angles with neutralizing effects that involve trimer destabilization. Optimizing these responses might provide an avenue to the induction of trimer dissociating bNAbs. IMPORTANCE Roughly 32 million people have died as a consequence of HIV-1 infection since the start of the epidemic and still 1.7 million people get infected with HIV-1 annually. Therefore, a vaccine to prevent HIV-1 infection is urgently needed. Current HIV-1 immunogens are not able to elicit the broad immune responses needed to provide protection against the large variation of HIV-1 strains circulating globally. A better understanding of the humoral immune responses elicited by immunization with state-of-the-art HIV-1 immunogens should facilitate the design of improved HIV-1 vaccine candidates. We identified antibodies with the ability to neutralize multiple HIV-1 viruses by destabilization of the envelope glycoprotein. Their weak but consistent cross-neutralization ability indicates the potential of this epitope to elicit broad responses. The trimer-destabilizing effect of the neutralizing mAbs combined with detailed characterization of the neutralization epitope can be used to shape the next generation of HIV-1 immunogens to elicit improved humoral responses after vaccination.

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