scholarly journals IgA dominates the early neutralizing antibody response to SARS-CoV-2

2020 ◽  
pp. eabd2223 ◽  
Author(s):  
Delphine Sterlin ◽  
Alexis Mathian ◽  
Makoto Miyara ◽  
Audrey Mohr ◽  
François Anna ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Immune Memory ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Virus Specific Antibody ◽  
Iga Response ◽  
Humoral Responses ◽  
Antibody Secreting Cells

Humoral immune responses are typically characterized by primary IgM antibody responses followed by secondary antibody responses associated with immune memory and comprised of of IgG, IgA and IgE. Here we measured acute humoral responses to SARS-CoV-2, including the frequency of antibody-secreting cells and the presence of SARS-CoV-2-specific neutralizing antibodies in the serum, saliva and broncho-alveolar fluid of 159 patients with COVID-19. Early SARS-CoV-2-specific humoral responses were dominated by IgA antibodies. Peripheral expansion of IgA plasmablasts with mucosal-homing potential was detected shortly after the onset of symptoms and peaked during the third week of the disease. The virus-specific antibody responses included IgG, IgM and IgA, but IgA contributed to virus neutralization to a greater extent compared with IgG. Specific IgA serum concentrations decreased notably one month after the onset of symptoms, but neutralizing IgA remained detectable in saliva for a longer time (days 49 to 73 post symptoms). These results represent a critical observation given the emerging information as to the types of antibodies associated with optimal protection against re-infection, and whether vaccine regimens should consider targeting a potent but potentially short-lived IgA response.

scholarly journals The vaccinia-based Sementis Copenhagen Vector COVID-19 vaccine induces broad and durable cellular and humoral immune responses

2021 ◽  
Author(s):  
Preethi Eldi ◽  
Tamara H Cooper ◽  
Natalie A Prow ◽  
Liang Liu ◽  
Gary K Heinemann ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
First Generation ◽  
Neutralizing Antibody ◽  
Immune Memory ◽  
Antibody Activity ◽  
Post Vaccination ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Heterologous Boost

The ongoing COVID-19 pandemic perpetuated by SARS-CoV-2 variants, has highlighted the continued need for broadly protective vaccines that elicit robust and durable protection. Here, the vaccinia virus-based, replication-defective Sementis Copenhagen Vector (SCV) was used to develop a first-generation COVID-19 vaccine encoding the spike glycoprotein (SCV-S). Vaccination of mice rapidly induced polyfunctional CD8 T cells with cytotoxic activity and robust Th1-biased, spike-specific neutralizing antibodies, which are significantly increased following a second vaccination, and contained neutralizing activity against the alpha and beta variants of concern. Longitudinal studies indicated neutralizing antibody activity was maintained up to 9 months post-vaccination in both young and aging mice, with durable immune memory evident even in the presence of pre-existing vector immunity. This immunogenicity profile suggests a potential to expand protection generated by current vaccines in a heterologous boost format, and presents a solid basis for second-generation SCV-based COVID-19 vaccine candidates incorporating additional SARS-CoV-2 immunogens.

scholarly journals Antibody responses in buffalos immunized with Clostridium perfringens beta and epsilon toxoids

2001 ◽  
Vol 46 (No. 9–10) ◽  
pp. 241-243 ◽  
Author(s):  
S. Rahman M ◽  
K. Baek B ◽  
T. Hong S ◽  
H. Lee J
Keyword(s):  
Antibody Titre ◽  
Clostridium Perfringens ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Control Group ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Antibody Titres ◽  
Group A ◽  
And Control

The antibody responses to toxoids were measured to investigate whether Clostridium perfringens beta and epsilon toxoids induced protective humoral immune responses in buffalos. Total of 24 buffalos were divided into 4 groups (n = 6), beta toxoid, epsilon toxoid, combination and control groups. These buffalo groups were administered each of the designated toxoids. Immunizations in the beta and epsilon toxoid groups induced strong antibody responses. The neutralizing antibody titres from the beta and epsilon toxoid groups were equally log101.2 on day 21 after inoculation whereas there was no antibody titre detected from the control group. A statistically significant (P < 0.01) increase in antibody titre was observed from day 0 to day 14 and 21 after inoculation. The antibody production did not vary significantly due to day of inoculation and toxoid interactions.

scholarly journals Purified Hexameric Epstein-Barr Virus-Encoded BARF1 Protein for Measuring Anti-BARF1 Antibody Responses in Nasopharyngeal Carcinoma Patients

2010 ◽  
Vol 18 (2) ◽  
pp. 298-304 ◽  
Author(s):  
E. K. Hoebe ◽  
S. H. Hutajulu ◽  
J. van Beek ◽  
S. J. Stevens ◽  
D. K. Paramita ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Antibody Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Humoral Immune ◽  
Barr Virus ◽  
Humoral Immune Responses ◽  
Human Sera ◽  
Epstein Barr ◽  
Humoral Responses

ABSTRACTWHO type III nasopharyngeal carcinoma (NPC) is highly prevalent in Indonesia and 100% associated with Epstein-Barr virus (EBV). NPC tumor cells express viral proteins, including BARF1, which is secreted and is considered to have oncogenic and immune-modulating properties. Recently, we found conserved mutations in the BARF1 gene in NPC isolates. This study describes the expression and purification of NPC-derived BARF1 and analyzes humoral immune responses against prototype BARF1 (B95-8) and purified native hexameric BARF1 in sera of Indonesian NPC patients (n= 155) compared to healthy EBV-positive (n= 56) and EBV-negative (n= 16) individuals. BARF1 (B95-8) expressed inEscherichia coliand baculovirus, as well as BARF1-derived peptides, did not react with IgG or IgA antibodies in NPC. Purified native hexameric BARF1 protein isolated from culture medium was used in enzyme-linked immunosorbent assay (ELISA) and revealed relatively weak IgG and IgA responses in human sera, although it had strong antibody responses to other EBV proteins. Higher IgG reactivity was found in NPC patients (P= 0.015) than in regional Indonesian controls or EBV-negative individuals (P< 0.001). IgA responses to native BARF1 were marginal. NPC sera with the highest IgG responses to hexameric BARF1 in ELISA showed detectable reactivity with denatured BARF1 by immunoblotting. In conclusion, BARF1 has low immunogenicity for humoral responses and requires native conformation for antibody binding. The presence of antibodies against native BARF1 in the blood of NPC patients provides evidence that the protein is expressed and secreted as a hexameric protein in NPC patients.

scholarly journals Fast and long-lasting immune response to S-trimer COVID-19 vaccine adjuvanted by PIKA

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Yuan Liu ◽  
Lianpan Dai ◽  
Xiaoli Feng ◽  
Ran Gao ◽  
Nan Zhang ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Candidate ◽  
Neutralizing Antibody ◽  
Protein Vaccine ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
The Face ◽  
Potential Vaccine ◽  
High Level

AbstractIn the face of the emerging variants of SARS-CoV-2, there is an urgent need to develop a vaccine that can induce fast, effective, long-lasting and broad protective immunity against SARS-CoV-2. Here, we developed a trimeric SARS-CoV-2 S protein vaccine candidate adjuvanted by PIKA, which can induce robust cellular and humoral immune responses. The results showed a high level of neutralizing antibodies induced by the vaccine was maintained for at least 400 days. In the study of non-human primates, PIKA adjuvanted S-trimer induced high SARS-CoV-2 neutralization titers and protected from virus replication in the lung following SARS-CoV-2 challenge. In addition, the long-term neutralizing antibody response induced by S-trimer vaccine adjuvanted by PIKA could neutralize multiple SARS-CoV-2 variants and there is no obvious different among the SARS- CoV-2 variants of interest or concern, including B.1.351, B.1.1.7, P.1, B.1.617.1 and B.1.617.2 variants. These data support the utility of S-trimer protein adjuvanted by PIKA as a potential vaccine candidate against SARS-CoV-2 infection.

scholarly journals Humoral protection to SARS-CoV2 declines faster in patients on TNF alpha blocking therapies

RMD Open ◽  
2021 ◽  
Vol 7 (3) ◽  
pp. e002008
Author(s):  
Ulf M Geisen ◽  
Melike Sümbül ◽  
Florian Tran ◽  
Dennis K Berner ◽  
Hayley M Reid ◽  
...  
Keyword(s):  
T Cell ◽  
Neutralizing Antibodies ◽  
Inflammatory Diseases ◽  
Cd4 T Cell ◽  
Vulnerable Groups ◽  
Humoral Immune ◽  
Vaccine Responses ◽  
Humoral Immune Responses ◽  
Disease Modifying ◽  
Humoral Responses

BackgroundThe persistence of the SARS-CoV2 pandemic, partly due to the appearance of highly infectious variants, has made booster vaccinations necessary for vulnerable groups. Questions remain as to which cohorts require SARS-CoV2 boosters. However, there is a critical lack of data on the dynamics of vaccine responses in patients with chronic inflammatory diseases (CID) undergoing immunosuppressive/disease modifying anti-rheumatic (DMARD) treatment. Here, we present the first data regarding the decline of the vaccine-induced humoral immune responses in patients with CID.Methods23 patients with CID were monitored clinically and for anti-spike IgG and IgA levels, neutralization efficacy and antigen-specific CD4+ T cell responses over the first 6 months after SARS-CoV2 vaccination. 24 healthy individuals were included as controls.ResultsWhile anti-spike IgG-levels declined in CID patients and healthy controls, patients receiving anti-TNF treatment showed significantly greater declines at 6 months post second vaccination in IgG and especially neutralizing antibodies. IgA levels were generally lower in CID patients, particularly during anti-TNF therapy. No differences in SARS-CoV2 spike-specific CD4+ T-cell frequencies were detected.ConclusionAlthough the long-term efficacy of SARS-CoV2 vaccination in CID patients undergoing disease-modifying therapy is still not known, the pronounced declines in humoral responses towards SARS-CoV2 6 months after mRNA vaccination in the context of TNF blockade should be considered when formulating booster regimens. These patients should be considered for early booster vaccinations.

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 SARS-CoV-2 naïve and recovered individuals show qualitatively different antibody responses following mRNA vaccination

2021 ◽  
Author(s):  
Sonia Tejedor Vaquero ◽  
Leire de Campos-Mata ◽  
José María Ramada ◽  
Pilar Díaz ◽  
Juan Navarro-Barriuso ◽  
...  
Keyword(s):  
Specific Antibody ◽  
Natural Infection ◽  
Neutralizing Antibody ◽  
Primary Vaccination ◽  
Antibody Responses ◽  
Specific Antibody Response ◽  
Vaccination Programs ◽  
Virus Specific Antibody ◽  
Compositional Patterns ◽  
Humoral Responses

mRNA-based vaccines effectively induce protective neutralizing antibody responses against SARS-CoV-2, the etiological agent of COVID-19. The specific compositional patterns of these responses remain largely unknown. We found that SARS-CoV-2-naïve individuals receiving the first dose of an mRNA vaccine developed a SARS-CoV-2-specific antibody response with a subclass profile comparable to that induced by the natural infection, except IgA2, which did not increase. SARS-CoV-2-naïve subjects also mounted a robust virus-specific recall response after receiving the second dose. This response increased all IgG subclasses, but boosted neither IgM nor IgA1 and IgA2 subclasses. In contrast, individuals recovered from COVID-19 mounted peak virus-specific antibody responses upon primary immunization and did not further augment such responses following secondary immunization. Remarkably, compared to SARS-CoV-2-naïve subjects, individuals with pre-existing immunity showed increased levels of all virus-specific antibodies but IgG3 following primary vaccination. By dissecting the heterogeneity of mRNA vaccine-induced humoral responses to SARS-CoV-2, our findings indicate that the induction of optimal immune protection may require the development of personalized vaccination programs.

scholarly journals Features and Functions of Systemic and Mucosal Humoral Immunity Among SARS-CoV-2 Convalescent Individuals

2020 ◽  
Author(s):  
Savannah E Butler ◽  
Andrew R Crowley ◽  
Harini Natarajan ◽  
Shiwei Xu ◽  
Joshua A Weiner ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Critical Role ◽  
Health Assessment ◽  
Inverse Correlation ◽  
Antibody Responses ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Mucosal Antibody ◽  
Assessment Strategies

Understanding humoral immune responses to SARS-CoV-2 infection will play a critical role in the development of vaccines and antibody-based interventions. We report systemic and mucosal antibody responses in convalescent individuals who experienced varying disease severity. Robust antibody responses to diverse SARS-CoV-2 antigens and evidence of elevated responses to endemic CoV were observed among convalescent donors. SARS-CoV-2-specific IgA and IgG responses were often negatively correlated, particularly in mucosal samples, suggesting subject-intrinsic biases in isotype switching. Assessment of antibody-mediated effector functions revealed an inverse correlation between systemic and mucosal neutralization activity and site-dependent differences in the isotype of neutralizing antibodies. Serum neutralization correlated with systemic anti-SARS-CoV-2 IgG and IgM response magnitude, while mucosal neutralization was associated with nasal SARS-CoV-2-specific IgA. These findings begin to map how diverse Ab characteristics relate to Ab functions and outcomes of infection, informing public health assessment strategies and vaccine development efforts.

scholarly journals Polystyrene nanoparticles induce stronger cellular and more durable humoral immune responses against an inactivated bovine herpesvirus 1 isolate

2020 ◽  
Author(s):  
Xingbo Liu ◽  
Zhihao Xin ◽  
Fan Zhang ◽  
Luyao zhang ◽  
Hanyu Yan ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Bovine Herpesvirus ◽  
Interferon Γ ◽  
Antibody Responses ◽  
Live Virus ◽  
Herpesvirus Type ◽  
Humoral Immune ◽  
Development Platform ◽  
Humoral Immune Responses

Abstract The inactivated bovine herpesvirus type 1(BoHV-1) vaccines are generally safe and suitable for use in dairy and pregnant cattle, but induces weaker cellular immune responses and shorter antibody responses compared with the modified live virus vaccine. In this study, we used polystyrene (PS) nanoparticles (100 nm) as a carrier for purified inactivated broken BoHV-1 to improve cellular and humoral immune responses compared with the traditional inactivated vaccine. Mice were injected intramuscularly with the inactivated complex mixed with ISA206 adjuvant. Transmission electron microscopy showed that the PS nanoparticles displayed broken BoHV-1 on their surfaces. After validation of BoHV-1 and gB gC gD gE tegument proteins, it proved that the BoHV-conjugated PS nanoparticles induced higher-titer and more durable antibody responses. The inactivated BoHV-PS nanoparticle complex elicited neutralizing antibodies (titer ~2 6 ) in 5 weeks post-immunization in mice. The CD4/CD8 ratio was higher in mice immunized with PS nanoparticles compared with other groups. However, this ratio reached its maximum 1 week later than in mice immunized with ISA206+BoHV-1 or BoHV-1. Levels of interleukin (IL)-4, IL-6, and interferon-γ in followed similar patterns. In conclusion, this pilot study demonstrated that PS nanoparticles can adjuvant inactivated BoHV-1 vaccines, enhancing both cell-mediated immune responses and the duration of antibody responses. This study provides the foundation for a new development platform for inactivated vaccines, which can elicit potent cellular and humoral immune responses in animals and humans.The inactivated bovine herpesvirus type 1(BoHV-1) vaccines are generally safe and suitable for use in dairy and pregnant cattle, but induces weaker cellular immune responses and shorter antibody responses compared with the modified live virus vaccine. In this study, we used polystyrene (PS) nanoparticles (100 nm) as a carrier for purified inactivated broken BoHV-1 to improve cellular and humoral immune responses compared with the traditional inactivated vaccine. Mice were injected intramuscularly with the inactivated complex mixed with ISA206 adjuvant. Transmission electron microscopy showed that the PS nanoparticles displayed broken BoHV-1 on their surfaces. After validation of BoHV-1 and gB gC gD gE tegument proteins, it proved that the BoHV-conjugated PS nanoparticles induced higher-titer and more durable antibody responses. The inactivated BoHV-PS nanoparticle complex elicited neutralizing antibodies (titer ~2 6 ) in 5 weeks post-immunization in mice. The CD4/CD8 ratio was higher in mice immunized with PS nanoparticles compared with other groups. However, this ratio reached its maximum 1 week later than in mice immunized with ISA206+BoHV-1 or BoHV-1. Levels of interleukin (IL)-4, IL-6, and interferon-γ in followed similar patterns. In conclusion, this pilot study demonstrated that PS nanoparticles can adjuvant inactivated BoHV-1 vaccines, enhancing both cell-mediated immune responses and the duration of antibody responses. This study provides the foundation for a new development platform for inactivated vaccines, which can elicit potent cellular and humoral immune responses in animals and humans.

scholarly journals Viral Replicative Capacity, Antigen Availability via Hematogenous Spread, and High TFH:TFRRatios Drive Induction of Potent Neutralizing Antibody Responses

2019 ◽  
Vol 93 (6) ◽  
Author(s):  
Preethi Eldi ◽  
Geeta Chaudhri ◽  
Stephen L. Nutt ◽  
Timothy P. Newsome ◽  
Gunasegaran Karupiah
Keyword(s):  
Immune Responses ◽  
Antibody Response ◽  
Germinal Center ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Replicative Capacity ◽  
Hematogenous Spread ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Early Predictor

ABSTRACTLive viral vaccines elicit protective, long-lived humoral immunity, but the underlying mechanisms through which this occurs are not fully elucidated. Generation of affinity matured, long-lived protective antibody responses involve close interactions between T follicular helper (TFH) cells, germinal center (GC) B cells, and T follicular regulatory (TFR) cells. We postulated that escalating concentrations of antigens from replicating viruses or live vaccines, spread through the hematogenous route, are essential for the induction and maintenance of long-lived protective antibody responses. Using replicating and poorly replicating or nonreplicating orthopox and influenza A viruses, we show that the magnitude of TFH cell, GC B cell, and neutralizing antibody responses is directly related to virus replicative capacity. Further, we have identified that both lymphoid and circulating TFH:TFRcell ratios during the peak GC response can be used as an early predictor of protective, long-lived antibody response induction. Finally, administration of poorly or nonreplicating viruses to allow hematogenous spread generates significantly stronger TFH:TFRratios and robust TFH, GC B cell and neutralizing antibody responses.IMPORTANCENeutralizing antibody response is the best-known correlate of long-term protective immunity for most of the currently licensed clinically effective viral vaccines. However, the host immune and viral factors that are critical for the induction of robust and durable antiviral humoral immune responses are not well understood. Our study provides insight into the dynamics of key cellular mediators of germinal center reaction during live virus infections and the influence of viral replicative capacity on the magnitude of antiviral antibody response and effector function. The significance of our study lies in two key findings. First, the systemic spread of even poorly replicating or nonreplicating viruses to mimic the spread of antigens from replicating viruses due to escalating antigen concentration is fundamental to the induction of durable antibody responses. Second, the TFH:TFRratio may be used as an early predictor of protective antiviral humoral immune responses long before memory responses are generated.

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