scholarly journals Persistent while declined neutralizing antibody responses in the convalescents of COVID-19 across clinical spectrum during the 16 months follow up

2021 ◽  
Author(s):  
Yang Yang ◽  
Minghui Yang ◽  
Yun Peng ◽  
Yanhua Liang ◽  
Jinli Wei ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Clinical Spectrum ◽  
Neutralizing Activity ◽  
Vaccination Strategies ◽  
Subsequent Decrease ◽  
Asymptomatic Infections ◽  
One Year ◽  
Kinetics Of

Elucidation the kinetics of neutralizing antibody response in the coronavirus disease 2019 (COVID-19) convalescents is crucial for the future control of the COVID-19 pandemic and vaccination strategies. Here we tested 411 sequential plasma samples collected up to 480 days post symptoms onset (d.a.o) from 214 convalescents of COVID-19 across clinical spectrum without re-exposure history after recovery and vaccination of SARS-CoV-2, using authentic SARS-CoV-2 microneutralization (MN) assays. COVID-19 convalescents free of re-exposure and vaccination could maintain relatively stable anti-RBD IgG and MN titers during 400~480 d.a.o after the peak at around 120 d.a.o and the subsequent decrease. Undetectable neutralizing activity started to occur in mild and asymptomatic infections during 330 to 480 d.a.o with an overall rate of 14.29% and up to 50% for the asymptomatic infections. Significant decline in MN titers was found in 91.67% COVID-19 convalescents with ≥ 50% decrease in MN titers when comparing the available peak and current MN titers (≥ 300 d.a.o). Antibody-dependent immunity could also provide protection against most of circulating variants after one year, while significantly decreased neutralizing activities against the Beta, Delta and Lambda variants were found in most of individuals. In summary, our results indicated that neutralizing antibody responses could last at least 480 days in most COVID-19 convalescents despite of the obvious decline of neutralizing activity, while the up to 50% undetectable neutralizing activity in the asymptomatic infections is of great concern.

scholarly journals Longitudinal evaluation and decline of antibody responses in SARS-CoV-2 infection

2020 ◽  
Author(s):  
Jeffrey Seow ◽  
Carl Graham ◽  
Blair Merrick ◽  
Sam Acors ◽  
Kathryn J.A. Steel ◽  
...  
Keyword(s):  
Disease Severity ◽  
Healthcare Workers ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Serum Samples ◽  
Vaccine Protection ◽  
Recent Emergence ◽  
Kinetics Of ◽  
Post Onset

Antibody (Ab) responses to SARS-CoV-2 can be detected in most infected individuals 10-15 days following the onset of COVID-19 symptoms. However, due to the recent emergence of this virus in the human population it is not yet known how long these Ab responses will be maintained or whether they will provide protection from re-infection. Using sequential serum samples collected up to 94 days post onset of symptoms (POS) from 65 RT-qPCR confirmed SARS-CoV-2-infected individuals, we show seroconversion in >95% of cases and neutralizing antibody (nAb) responses when sampled beyond 8 days POS. We demonstrate that the magnitude of the nAb response is dependent upon the disease severity, but this does not affect the kinetics of the nAb response. Declining nAb titres were observed during the follow up period. Whilst some individuals with high peak ID50 (>10,000) maintained titres >1,000 at >60 days POS, some with lower peak ID50 had titres approaching baseline within the follow up period. A similar decline in nAb titres was also observed in a cohort of seropositive healthcare workers from Guy′s and St Thomas′ Hospitals. We suggest that this transient nAb response is a feature shared by both a SARS-CoV-2 infection that causes low disease severity and the circulating seasonal coronaviruses that are associated with common colds. This study has important implications when considering widespread serological testing, Ab protection against re-infection with SARS-CoV-2 and the durability of vaccine protection.

scholarly journals Continuous HIV-1 Escape from Autologous Neutralization and Development of Cross-Reactive Antibody Responses Characterizes Slow Disease Progression of Children

Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 260
Author(s):  
Stefania Dispinseri ◽  
Mariangela Cavarelli ◽  
Monica Tolazzi ◽  
Anna Maria Plebani ◽  
Marianne Jansson ◽  
...  
Keyword(s):  
Disease Progression ◽  
Antibody Responses ◽  
Viral Escape ◽  
Target Cells ◽  
Transmitted Virus ◽  
Slow Progressors ◽  
Vaccine Antigens ◽  
Kinetics Of ◽  
Hiv 1

The antibodies with different effector functions evoked by Human Immunodeficiency Virus type 1 (HIV-1) transmitted from mother to child, and their role in the pathogenesis of infected children remain unresolved. So, too, the kinetics and breadth of these responses remain to be clearly defined, compared to those developing in adults. Here, we studied the kinetics of the autologous and heterologous neutralizing antibody (Nab) responses, in addition to antibody-dependent cellular cytotoxicity (ADCC), in HIV-1 infected children with different disease progression rates followed from close after birth and five years on. Autologous and heterologous neutralization were determined by Peripheral blood mononuclear cells (PBMC)- and TZMbl-based assays, and ADCC was assessed with the GranToxiLux assay. The reactivity to an immunodominant HIV-1 gp41 epitope, and childhood vaccine antigens, was assessed by ELISA. Newborns displayed antibodies directed towards the HIV-1 gp41 epitope. However, antibodies neutralizing the transmitted virus were undetectable. Nabs directed against the transmitted virus developed usually within 12 months of age in children with slow progression, but rarely in rapid progressors. Thereafter, autologous Nabs persisted throughout the follow-up of the slow progressors and induced a continuous emergence of escape variants. Heterologous cross-Nabs were detected within two years, but their subsequent increase in potency and breadth was mainly a trait of slow progressors. Analogously, titers of antibodies mediating ADCC to gp120 BaL pulsed target cells increased in slow progressors during follow-up. The kinetics of antibody responses to the immunodominant viral antigen and the vaccine antigens were sustained and independent of disease progression. Persistent autologous Nabs triggering viral escape and an increase in the breadth and potency of cross-Nabs are exclusive to HIV-1 infected slowly progressing children.

scholarly journals Declining Levels of Neutralizing Antibodies Against SARS-CoV-2 in Convalescent COVID-19 Patients One Year Post Symptom Onset

2021 ◽  
Vol 12 ◽  
Author(s):  
Tiandan Xiang ◽  
Boyun Liang ◽  
Yaohui Fang ◽  
Sihong Lu ◽  
Sumeng Li ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Neutralizing Antibodies ◽  
Natural Infection ◽  
Protein S ◽  
Igg Antibodies ◽  
Neutralizing Activity ◽  
Specific Igg ◽  
One Year ◽  
Kinetics Of

Major advances have been made in understanding the dynamics of humoral immunity briefly after the acute coronavirus disease 2019 (COVID-19). However, knowledge concerning long-term kinetics of antibody responses in convalescent patients is limited. During a one-year period post symptom onset, we longitudinally collected 162 samples from 76 patients and quantified IgM and IgG antibodies recognizing the nucleocapsid (N) protein or the receptor binding domain (RBD) of the spike protein (S). After one year, approximately 90% of recovered patients still had detectable SARS-CoV-2-specific IgG antibodies recognizing N and RBD-S. Intriguingly, neutralizing activity was only detectable in ~43% of patients. When neutralization tests against the E484K-mutated variant of concern (VOC) B.1.351 (initially identified in South Africa) were performed among patients who neutralize the original virus, the capacity to neutralize was even further diminished to 22.6% of donors. Despite declining N- and S-specific IgG titers, a considerable fraction of recovered patients had detectable neutralizing activity one year after infection. However, neutralizing capacities, in particular against an E484K-mutated VOC were only detectable in a minority of patients one year after symptomatic COVID-19. Our findings shed light on the kinetics of long-term immune responses after natural SARS-CoV-2 infection and argue for vaccinations of individuals who experienced a natural infection to protect against emerging VOC.

scholarly journals Function is more reliable than quantity to follow up the humoral response to the Receptor Binding Domain of SARS- CoV-2 Spike Protein after Natural Infection or COVID-19 vaccination

2021 ◽  
Author(s):  
Carlos A Sariol ◽  
Petraleigh Pantoja ◽  
Crisanta Serrano-Collazo ◽  
Tiffant Rosa-Arocho ◽  
Albersy Armina ◽  
...  
Keyword(s):  
Immune Response ◽  
Neutralizing Antibodies ◽  
Natural Infection ◽  
Vaccine Dose ◽  
Humoral Response ◽  
Neutralizing Antibody ◽  
Viral Neutralization ◽  
Neutralizing Activity ◽  
Robust Immune Response

On this work we report that despite of a decline in the total anti-Spike antibodies the neutralizing antibodies remains at a similar level for an average of 98 days in a longitudinal cohort of 59 Hispanic/Latino exposed to SARS-CoV-2. We are also reporting that the percentage of neutralization correlates with the IgG titers and that in the first collected samples, IgG1 was the predominant isotype (62.71%), followed by IgG4 (15.25%), IgG3 (13.56%), and IgG2 (8.47%) during the tested period. The IgA was detectable in 28.81% of subjects. Only 62.71% of all subjects have detectable IgM in the first sample despite of confirmed infection by a molecular method. Our data suggests that 100% that seroconvert make detectable neutralizing antibody responses measured by a surrogate viral neutralization test. We also found that the IgG titers and neutralizing activity were higher after the first dose in 10 vaccinated subjects out of the 59 with prior infection compare to a subgroup of 21 subjects naive to SARS-CoV-2. One dose was enough but two were necessary to reach the maximum percentage of neutralization in subjects with previous natural infection or naive to SARS-CoV-2 respectively. Like the pattern seen after the natural infection, after the second vaccine dose, the total anti-S antibodies and titers declined but not the neutralizing activity which remains at same levels for more than 80 days after the first vaccine dose. That decline, however, was significantly lower in pre-exposed individuals which denotes the contribution of the natural infection priming a more robust immune response to the vaccine. Also, our data indicates that the natural infection induces a more robust humoral immune response than the first vaccine dose in unexposed subjects. However, the difference was significant only when the neutralization was measured but not by assessing the total anti-S antibodies or the IgG titers. This work is an important contribution to understand the natural immune response to the novel coronavirus in a population severely hit by the virus. Also provide an invaluable data by comparing the dynamic of the immune response after the natural infection vs. the vaccination and suggesting that a functional test is a better marker than the presence or not of antibodies. On this context our results are also highly relevant to consider standardizing methods that in addition to serve as a tool to follow up the immune response to the vaccines may also provide a correlate of protection.

scholarly journals Weak Cross-Lineage Neutralization by Anti SARS-CoV-2 Spike Antibodies after Natural Infection or Vaccination Is Rescued by Repeated Immunological Stimulation

Vaccines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1124
Author(s):  
Sara Caucci ◽  
Benedetta Corvaro ◽  
Sofia Maria Luigia Tiano ◽  
Anna Valenza ◽  
Roberta Longo ◽  
...  
Keyword(s):  
Single Dose ◽  
Natural Infection ◽  
Neutralizing Antibody ◽  
Natural Immunity ◽  
Anamnestic Response ◽  
Neutralizing Activity ◽  
Immunological Markers ◽  
The Cross ◽  
One Year

After over one year of evolution, through billions of infections in humans, SARS-CoV-2 has evolved into a score of slightly divergent lineages. A few different amino acids in the spike proteins of these lineages can hamper both natural immunity against reinfection, and vaccine efficacy. In this study, the in vitro neutralizing potency of sera from convalescent COVID-19 patients and vaccinated subjects was analyzed against six different SARS-CoV-2 lineages, including the latest B.1.617.2 (or Delta variant), in order to assess the cross-neutralization by anti-spike antibodies. After both single dose vaccination, or natural infection, the neutralizing activity was low and fully effective only against the original lineage, while a double dose or a single dose of vaccine, even one year after natural infection, boosted the cross-neutralizing activity against different lineages. Neither binding, nor the neutralizing activity of sera after vaccination, could predict vaccine failure, underlining the need for additional immunological markers. This study points at the importance of the anamnestic response and repeated vaccine stimulations to elicit a reasonable cross-lineage neutralizing antibody response.

scholarly journals THE FORMATION AND PROPERTIES OF POLIOVIRUS-NEUTRALIZING ANTIBODY

1964 ◽  
Vol 119 (1) ◽  
pp. 21-39 ◽  
Author(s):  
Sven-Eric Svehag ◽  
Benjamin Mandel
Keyword(s):  
Antibody Formation ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Whole Body ◽  
High Dose ◽  
Antibody Synthesis ◽  
Antigen Dose ◽  
X Irradiation ◽  
Virus C ◽  
Kinetics Of

Transient 19S antibody formation was induced in rabbits by single or repeated stimuli with a small dose of poliovirus. Available evidence indicated that cessation of 19S synthesis was due to lack of continuous antigenic stimulation and not to loss of cells participating in antibody formation. "Immunological memory" in 19S antibody formation was demonstrable only within 2 to 3 days following discontinuation of synthesis but not thereafter. Following stimulation with a high dose of polio-virus both 19S and 7S antibodies were formed. The kinetics of their formation differed in several respects: (a) 19S antibody preceded 7S antibody by ⩾1½ days; (b) 19S antibody rose to peak titers at a rapid exponential rate within 1 week, while 7S antibody increased at a slow decelerating rate for ⩽3 weeks; (c) 19S antibody formation was short-lasting while 7S antibody synthesis endured. A renewed formation of both antibodies occurred following restimulation with a high antigen dose. The secondary 19S and 7S antibody responses were similar to the respective primary responses, and the preexistence of 7S antibody synthesis did not detectably alter the secondary 19S response. Both 19S and 7S antibodies were formed and the kinetics of their formation was similar (a) for infectious and non-infectious (UV-) poliovirus antigen; (b) for the serologically unrelated poliovirus and Coxsackie B-4 virus; (c) when poliovirus was administered by different routes; (d) when 1-day-old or adult rabbits were immunized; (e) in antibody responses to poliovirus in rabbit, guinea pig, and man. Whole body x-irradiation 20 hours prior to antigenic stimulus (high dose) resulted in delayed but markedly prolonged 19S antibody formation and inhibition of 7S antibody synthesis. Thus, the formation of 19S and 7S antibody differed in (a) antigen dose requirements for induction and maintained synthesis; (b) kinetics; (c) retention of memory; and (d) sensitivity to prior x-irradiation. These differences are best explained on the assumption that the two antibodies are produced by different cells.

scholarly journals Neutralizing antibody titres in SARS-CoV-2 infections

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Eric H. Y. Lau ◽  
Owen T. Y. Tsang ◽  
David S. C. Hui ◽  
Mike Y. W. Kwan ◽  
Wai-hung Chan ◽  
...  
Keyword(s):  
Severe Disease ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Global Public Health ◽  
Rt Pcr ◽  
Asymptomatic Patients ◽  
Antibody Titres ◽  
Observational Cohort ◽  
Public Health Challenge ◽  
Asymptomatic Infections

AbstractThe SARS-CoV-2 pandemic poses the greatest global public health challenge in a century. Neutralizing antibody is a correlate of protection and data on kinetics of virus neutralizing antibody responses are needed. We tested 293 sera from an observational cohort of 195 reverse transcription polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2 infections collected from 0 to 209 days after onset of symptoms. Of 115 sera collected ≥61 days after onset of illness tested using plaque reduction neutralization (PRNT) assays, 99.1% remained seropositive for both 90% (PRNT90) and 50% (PRNT50) neutralization endpoints. We estimate that it takes at least 372, 416 and 133 days for PRNT50 titres to drop to the detection limit of a titre of 1:10 for severe, mild and asymptomatic patients, respectively. At day 90 after onset of symptoms (or initial RT-PCR detection in asymptomatic infections), it took 69, 87 and 31 days for PRNT50 antibody titres to decrease by half (T1/2) in severe, mild and asymptomatic infections, respectively. Patients with severe disease had higher peak PRNT90 and PRNT50 antibody titres than patients with mild or asymptomatic infections. Age did not appear to compromise antibody responses, even after accounting for severity. We conclude that SARS-CoV-2 infection elicits robust neutralizing antibody titres in most individuals.

scholarly journals SARS-CoV-2 antibodies remain detectable 12 months after infection and antibody magnitude is associated with age and COVID-19 severity

2021 ◽  
Author(s):  
Eric D. Laing ◽  
Nusrat J. Epsi ◽  
Stephanie A. Richard ◽  
Emily C. Samuels ◽  
Wei Wang ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Neutralizing Antibodies ◽  
Natural Infection ◽  
Geometric Mean ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Serum Samples ◽  
Military Hospitals ◽  
Igg Binding ◽  
One Year

ABSTRACTImportanceThe persistence of SARS-CoV-2 antibodies may be a predictive correlate of protection for both natural infections and vaccinations. Identifying predictors of robust antibody responses is important to evaluate the risk of re-infection / vaccine failure and may be translatable to vaccine effectiveness.ObjectiveTo 1) determine the durability of anti-SARS-CoV-2 IgG and neutralizing antibodies in subjects who experienced mild and moderate to severe COVID-19, and 2) to evaluate the correlation of age and IgG responses to both endemic human seasonal coronaviruses (HCoVs) and SARS-CoV-2 according to infection outcome.DesignLongitudinal serum samples were collected from PCR-confirmed SARS-CoV-2 positive participants (U.S. active duty service members, dependents and military retirees, including a range of ages and demographics) who sought medical treatment at seven U.S. military hospitals from March 2020 to March 2021 and enrolled in a prospective observational cohort study.ResultsWe observed SARS-CoV-2 seropositivity in 100% of inpatients followed for six months (58/58) to one year (8/8), while we observed seroreversion in 5% (9/192) of outpatients six to ten months after symptom onset, and 18% (2/11) of outpatients followed for one year. Both outpatient and inpatient anti-SARS-CoV-2 binding-IgG responses had a half-life (T1/2) of >1000 days post-symptom onset. The magnitude of neutralizing antibodies (geometric mean titer, inpatients: 378 [246-580, 95% CI] versus outpatients: 83 [59-116, 95% CI]) and durability (inpatients: 65 [43-98, 95% CI] versus outpatients: 33 [26-40, 95% CI]) were associated with COVID-19 severity. Older age was a positive correlate with both higher IgG binding and neutralizing antibody levels when controlling for COVID-19 hospitalization status. We found no significant relationships between HCoV antibody responses and COVID-19 clinical outcomes, or the development of SARS-CoV-2 neutralizing antibodies.Conclusions and RelevanceThis study demonstrates that humoral responses to SARS-CoV-2 infection are robust on longer time-scales, including those arising from milder infections.However, the magnitude and durability of the antibody response after natural infection was lower and more variable in younger participants who did not require hospitalization for COVID-19. These findings support vaccination against SARS-CoV-2 in all suitable populations including those individuals that have recovered from natural infection.

scholarly journals Phage-like particle vaccines are highly immunogenic and protect against pathogenic coronavirus infection and disease

2021 ◽  
Author(s):  
Bennett J Davenport ◽  
Alexis Catala ◽  
Stuart M Weston ◽  
Robert M Johnson ◽  
Jeremy Ardunay ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Live Virus ◽  
Physiochemical Properties ◽  
Multivalent Display ◽  
Specific Igg ◽  
Coronavirus Infection ◽  
Rapid Generation ◽  
One Year ◽  
Antibody Levels

The response by vaccine developers to the COVID-19 pandemic has been extraordinary with effective vaccines authorized for emergency use in the U.S. within one year of the appearance of the first COVID-19 cases. However, the emergence of SARS-CoV-2 variants and obstacles with the global rollout of new vaccines highlight the need for platforms that are amenable to rapid tuning and stable formulation to facilitate the logistics of vaccine delivery worldwide. We developed a designer nanoparticle platform using phage-like particles (PLPs) derived from bacteriophage lambda for multivalent display of antigens in rigorously defined ratios. Here, we engineered PLPs that display the receptor binding domain (RBD) protein from SARS-CoV-2 and MERS-CoV, alone (RBD-SARS-PLPs, RBD-MERS-PLPs) and in combination (hCoV-RBD PLPs). Functionalized particles possess physiochemical properties compatible with pharmaceutical standards and retain antigenicity. Following primary immunization, BALB/c mice immunized with RBD-SARS- or RBD-MERS-PLPs display serum RBD-specific IgG endpoint and live virus neutralization titers that, in the case of SARS-CoV-2, were comparable to those detected in convalescent plasma from infected patients. Further, these antibody levels remain elevated up to 6 months post-prime. In dose response studies, immunization with as little as one microgram of RBD-SARS-PLPs elicited robust neutralizing antibody responses. Finally, animals immunized with RBD-SARS-PLPs, RBD-MERS-PLPs, and hCoV-RBD PLPs were protected against SARS-CoV-2 and/or MERS-CoV lung infection and disease. Collectively, these data suggest that the designer PLP system provides a platform for facile and rapid generation of single and multi-target vaccines.

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