ABSTRACT
We analyzed the kinetics and durability of the humoral responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination using >8,000 longitudinal samples collected over a three-year period (April 2020 to April 2023) in the New York City metropolitan area. Upon primary immunization, participants with pre-existing immunity mounted higher antibody responses faster and achieved higher steady-state levels compared to naive individuals. Antibody durability was characterized by two phases: an initial rapid decay, followed by a phase of stabilization with very slow decay resulting in an individual spike binding antibody steady state. Booster vaccination equalized the differences in antibody levels between participants with and without hybrid immunity, but the antibody titers reached decreased with each successive antigen exposure. Break-through infections increased antibody titers to similar levels as an additional vaccine dose in naive individuals. Our study provides strong evidence for the fact that SARS-CoV-2 antibody responses are long lasting, with an initial waning phase followed by a stabilization phase.
Subject(s)
COVID-19 , Coronavirus InfectionsABSTRACT
Coronavirus disease 2019 (COVID-19) vaccines have saved millions of lives. However, variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged causing large numbers of breakthrough infections. These developments necessitated the rollout of COVID-19 vaccine booster doses. It has been reported that mucosal antibody levels in the upper respiratory tract, especially for secretory IgA (sIgA), correlate with protection from infection with SARS-CoV-2. However, it is still unclear how high levels of mucosal antibodies can be induced. In this study, we measured serum IgG, saliva IgG and saliva sIgA responses in individuals who received COVID-19 mRNA booster vaccinations or who experienced breakthrough infections. We found that mRNA booster doses could induce robust serum and saliva IgG responses, especially in individuals who had not experienced infections before, but saliva sIgA responses were weak. In contrast, breakthrough infections in individuals who had received the primary mRNA vaccination series induced robust serum and saliva IgG as well as saliva sIgA responses. Individuals who had received a booster dose and then had a breakthrough infection showed low IgG induction in serum and saliva but still responded with robust saliva sIgA induction. These data suggest that upper respiratory tract exposure to antigen is an efficient way of inducing mucosal sIgA while exposure via intramuscular injection is not.
Subject(s)
Coronavirus Infections , Breakthrough Pain , COVID-19ABSTRACT
The Orthocoronaviridae subfamily is large comprising four highly divergent genera. Four seasonal coronaviruses were circulating in humans prior to the coronavirus disease 2019 (COVID-19) pandemic. Infection with these viruses induced antibody responses that are relatively narrow with little cross-reactivity to spike proteins of other coronaviruses. Here, we report that infection with and vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces broadly crossreactive binding antibodies to spikes from a wide range of coronaviruses including members of the sarbecovirus subgenus, betacoronaviruses including Middle Eastern respiratory syndrome coronavirus (MERS CoV), and extending to alpha-, gamma- and delta-coronavirus spikes. These data show that the coronavirus spike antibody landscape in humans has profoundly been changed and broadened as a result of the SARS-CoV-2 pandemic. While we do not understand the functionality of these crossreactive antibodies, they may lead to enhanced resistance of the population to infection with newly emerging coronaviruses with pandemic potential.
Subject(s)
COVID-19 , Coronavirus InfectionsABSTRACT
The question if the bivalent mRNA COVID-19 booster vaccination, containing wild type and BA.5 spike, provides enhanced benefits against BA.5 and similar Omicron subvariants has been widely debated. One concern was an original antigenic sin-like effect which may redirect immune responses to the bivalent vaccine towards the wild type spike and may block de novo generation of BA.5 specific antibodies. Here, we characterized the response to the bivalent vaccine and we performed antibody depletion experiments. Interestingly, when we depleted serum of all antibodies to wild type RBD, we also removed all reactivity to BA.5 RBD. This suggests that all antibodies induced by the bivalent vaccine - at least with the limit of detection of our assay in polyclonal serum - are in fact cross-reactive. This further suggests that, on a serum antibody level, the bivalent vaccine did not induce a de novo response to BA.5.
Subject(s)
COVID-19ABSTRACT
Medicines play a vital role in human lives and that’s why the market size of medicines is quite large. Amid the pandemic of COVID-19 in the 21st century, the governments of many countries as well as healthcare industries, hospitals, doctors, and patients are facing a crucial threat of tampering and counterfeiting of vaccines and drugs. This is not an issue that can be ignored easily, as it troubles all of society in a significant way. New technology such as near field communication (NFC), combined with the latest technologies such as Hyperledger, blockchain, and the Internet of Things have given efficient results. The methodology used in this research manuscript (the authors named it “AKSHAT”) is that an NFC chip will be installed in the caps of medicines. When a consumer scans the label on a product with a phone or any NFC-enabled device, the device authenticates the product and informs as to whether it is a genuine product. When a consumer finds that the NFC seal is broken or if it looks intact but NFC data cannot be read, then apparently the product has been tampered with. In NFC, all data and information can be stored and cannot be changed again. The research results presented here establish that NFC is time-efficient, cost-effective, secure, and accurate. With the use of NFC tags, registered transactions on a private network and the tracing of the vaccine are very easy. The authors’ team has demonstrated this as a product that can currently store every transaction as immutable and transparent. The proposed anticounterfeiting solution “AKSHAT” uses NTAG-213 based tags, which are cost-effective as well as have a mutual understanding with all NFC-enabled smartphones. This provides the option for all product manufacturers and brand owners to integrate NFC technology at a fraction of the money. © 2022 Elsevier Inc. All rights reserved.
ABSTRACT
Background: Better understanding of the association between characteristics of patients hospital-ized with coronavirus disease 2019 (COVID-19) and outcome is needed to further improve upon patient management. Methods: Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) is a prospective, observational study of 1,164 patients from 20 hospitals across the United States. Disease severi-ty was assessed using a 7-point ordinal scale based on degree of respiratory illness. Patients were prospectively surveyed for 1 year after discharge for post-acute sequalae of COVID-19 (PASC) through quarterly surveys. Demographics, comorbidities, radiographic findings, clinical laboratory values, SARS-CoV-2 PCR and serology were captured over a 28-day period. Multi-variable logistic regression was performed. Findings: The median age was 59 years (interquartile range [IQR] 20); 711 (61%) were men; overall mortality was 14%, and 228 (20%) required invasive mechanical ventilation. Unsuper-vised clustering of ordinal score over time revealed distinct disease course trajectories. Risk fac-tors associated with prolonged hospitalization or death by day 28 included age [≥] 65 years (odds ratio [OR], 2.01; 95% CI 1.28-3.17), Hispanic ethnicity (OR, 1.71; 95% CI 1.13-2.57), elevated baseline creatinine (OR 2.80; 95% CI 1.63- 4.80) or troponin (OR 1.89; 95% 1.03-3.47), baseline lymphopenia (OR 2.19; 95% CI 1.61-2.97), presence of infiltrate by chest imaging (OR 3.16; 95% CI 1.96-5.10), and high SARS-CoV2 viral load (OR 1.53; 95% CI 1.17-2.00). Fatal cases had the lowest ratio of SARS-CoV-2 antibody to viral load levels compared to other trajectories over time (p=0.001). 589 survivors (51%) completed at least one survey at follow-up with 305 (52%) hav-ing at least one symptom consistent with PASC, most commonly dyspnea (56% among symp-tomatic patients). Female sex was the only associated risk factor for PASC. Interpretation: Integration of PCR cycle threshold, and antibody values with demographics, comorbidities, and laboratory/radiographic findings identified risk factors for 28-day outcome severity, though only female sex was associated with PASC. Longitudinal clinical phenotyping offers important insights, and provides a framework for immunophenotyping for acute and long COVID-19. Funding: NIH
Subject(s)
COVID-19 , Lymphopenia , Dyspnea , Respiratory InsufficiencyABSTRACT
AO_SCPLOWBSTRACTC_SCPLOWPersistent SARS-CoV-2 infections have been reported in immune-compromised individuals and people undergoing immune-modulatory treatments. It has been speculated that the emergence of antigenically diverse SARS-CoV-2 variants such as the Omicron variant may be the result of intra-host viral evolution driven by suboptimal immune responses, which must be followed by forward transmission. However, while intrahost evolution has been documented, to our knowledge no direct evidence of subsequent forward transmission is available to date. Here we describe the emergence of an Omicron BA.1 sub-lineage with 8 additional amino acid substitutions within the spike (E96D, L167T, R346T, L455W, K458M, A484V, H681R, A688V) in an immune-compromised host along with evidence of 5 forward transmission cases. Our findings show that the Omicron BA.1 lineage can further diverge from its exceptionally mutated genome during prolonged SARS-CoV-2 infection; highlighting an urgent need to employ therapeutic strategies to limit duration of infection and spread in vulnerable patients.
Subject(s)
COVID-19 , Severe Acute Respiratory SyndromeABSTRACT
Two messenger RNA (mRNA)-based vaccines are widely used globally to prevent coronavirus disease 2019 (COVID-19). Both vaccine formulations contain PEGylated lipids in their composition, in the form of polyethylene glycol [PEG] 2000 dimyristoyl glycerol for mRNA-1273, and 2 [(polyethylene glycol)-2000]-N,N-ditetradecylacetamide for BNT162b2. It is known that some PEGylated drugs and products for human use that contain PEG, are capable of eliciting immune responses, leading to detectable PEG-specific antibodies in serum. In this study, we determined if any of the components of mRNA-1273 or BNT162b2 formulations elicited PEG-specific antibody responses in serum by enzyme linked immunosorbent assay (ELISA). We detected an increase in the reactivity to mRNA vaccine formulations in mRNA-1273 but not BNT162b2 vaccinees sera in a prime-boost dependent manner. Furthermore, we observed the same pattern of reactivity against irrelevant lipid nanoparticles from an influenza virus mRNA formulation and found that the reactivity of such antibodies correlated well with antibody levels against high and low molecular weight PEG. Using sera from participants selected based on the vaccine-associated side effects experienced after vaccination, including delayed onset, injection site or severe allergic reactions, we found no obvious association between PEG antibodies and adverse reactions. Overall, our data shows a differential induction of anti-PEG antibodies by mRNA-1273 and BNT162b2. The clinical relevance of PEG reactive antibodies induced by administration of the mRNA-1273 vaccine, and the potential interaction of these antibodies with other PEGylated drugs remains to be explored.
Subject(s)
COVID-19 , Drug HypersensitivityABSTRACT
The PARIS (Protection Associated with Rapid Immunity to SARS-CoV-2) cohort follows health care workers with and without documented coronavirus disease 2019 (COVID-19) since April 2020. We report our findings regarding SARS-CoV-2 spike binding antibody stability and protection from infection in the pre-variant era. We analyzed data from 400 healthcare workers (150 seropositive and 250 seronegative at enrollment) for a median of 84 days. The SARS-CoV-2 spike binding antibody titers were highly variable with antibody levels decreasing over the first three months, followed by a relative stabilization. We found that both more advanced age (>40 years) and female sex were associated with higher antibody levels (1.6-fold and 1.4-fold increases, respectively). Only six percent of the initially seropositive participants "seroreverted". We documented a total of 11 new SARS-CoV-2 infections (ten naive participants, one previously infected participant without detectable antibodies, p<0.01) indicating that spike antibodies limit the risk of re-infection. These observations, however, only apply to SARS-CoV-2 variants antigenically similar to the ancestral SARS-CoV-2 ones. In conclusion, SARS-CoV-2 antibody titers mounted upon infection are stable over several months in most people and provide protection from infection with antigenically similar viruses.
Subject(s)
Severe Acute Respiratory Syndrome , COVID-19ABSTRACT
NDV-HXP-S is a recombinant Newcastle disease virus based-vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which expresses an optimized (HexaPro) spike protein on its surface. The vaccine can be produced in embryonated chicken eggs using the same process as that employed for the production of influenza virus vaccines. Here we performed a secondary analysis of the antibody responses after vaccination with inactivated NDV-HXP-S in a Phase I clinical study in Thailand. The SARS-CoV-2 neutralizing and spike binding activity of NDV-HXP-S post-vaccination serum samples was compared to that of matched samples from mRNA BNT162b2 (Pfizer) vaccinees. Neutralizing activity of sera from NDV-HXP-S vaccinees was comparable to that of individuals vaccinated with BNT162b2. Interstingly, the spike binding activity of the NDV-HXP-S vaccinee samples was lower than that of sera obtained from individuals vaccinated with the mRNA vaccine. This let us to calculate ratios between binding and neutralizing antibody titers. Samples from NDV-HXP-S vaccinees had binding to neutralizing activity ratios similar to those of convalescent sera suggesting a very high proportion of neutralizing antibodies and low non-neutralizing antibody titers. Further analysis showed that, in contrast to mRNA vaccination, which induces strong antibody titers to the receptor binding domain (RBD), the N-terminal domain, and the S2 domain, NDV-HXP-S vaccination induces a very RBD focused response with little reactivity to S2. This explains the high proportion of neutralizing antibodies since most neutralizing epitopes are located in the RBD. In conclusion, vaccination with inactivated NDV-HXP-S induces a high proportion of neutralizing antibodies and absolute neutralizing antibody titers comparable to those after mRNA vaccination.
Subject(s)
COVID-19 , Coronavirus InfectionsABSTRACT
The B.1.1.529 (Omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in November of 2021 in South Africa and Botswana as well as in a sample of a traveler from South Africa in Hong Kong.1,2 Since then, B.1.1.529 has been detected in many countries globally. This variant seems to be more infectious than B.1.617.2 (Delta), has already caused super spreader events3 and has outcompeted Delta within weeks in several countries and metropolitan areas. B.1.1.529 hosts an unprecedented number of mutations in its spike gene and early reports have provided evidence for extensive immune escape and reduced vaccine effectiveness.2,4-6 Here, we investigated the neutralizing and binding activity of sera from convalescent, mRNA double vaccinated, mRNA boosted as well as convalescent double vaccinated and convalescent boosted individuals against wild type, B.1.351 and B.1.1.529 SARS-CoV-2 isolates. Neutralizing activity of sera from convalescent and double vaccinated participants was undetectable to very low against B.1.1.529 while neutralizing activity of sera from individuals who had been exposed to spike three or four times was maintained, albeit at strongly reduced levels. Binding to the B.1.1.529 receptor binding domain (RBD) and N-terminal domain (NTD) was reduced in convalescent not vaccinated but was mostly retained in vaccinated individuals.
Subject(s)
Coronavirus InfectionsABSTRACT
Mucosal 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.
Subject(s)
COVID-19 , Coronavirus Infections , Respiratory Tract InfectionsABSTRACT
Highly efficacious vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed.1 However, the emergence of viral variants that are more infectious than the earlier SARS-CoV-2 strains is concerning.2 Several of these viral variants have the potential to partially escape neutralizing antibody responses warranting continued immune-monitoring. Here, we tested a number of currently circulating viral variants of concern/interest, including B.1.526 (Iota), B.1.1.7+E484K (Alpha), B.1.351 (Beta), B.1.617.2 (Delta) and C.37 (Lambda) in neutralization assays using a panel of post-mRNA vaccination sera. The assays were performed with authentic SARS-CoV-2 clinical isolates in an assay that mimics physiological conditions. We found only small decreases in neutralization against B.1.526 and an intermediate phenotype for B.617.2. The reduction was stronger against a sub-variant of C.37, followed by B.1.351 and B.1.1.7+E484K. C.37 is currently circulating in parts of Latin America3 and was detected in Germany, the US and Israel. Of note, reduction in a binding assay that also included P.1, B.1.617.1 (Kappa) and A.23.1 was negligible. Taken together, these findings suggest that mRNA SARS-CoV-2 vaccines may remain effective against these viral variants of concern/interest and that spike binding antibody tests likely retain specificity in the face of evolving SARS-CoV-2 diversity.
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are highly effective in healthy individuals. Patients with multiple myeloma (MM) are immunocompromised due to defects in humoral and cellular immunity as well as immunosuppressive therapies. The efficacy after two doses of SARS-CoV-2 mRNA vaccination in MM patients is currently unknown. Here, we report the case of a MM patient who developed a fatal SARS-CoV-2 infection after full vaccination while in remission after B cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR)-T treatment. We show that the patient failed to generate antibodies or SARS-CoV-2-specific B and T cell responses, highlighting the continued risk of severe coronavirus disease 2019 (COVID-19) in vaccine non-responders. In the largest cohort of vaccinated MM patients to date, we demonstrate that 15.9% lack SARS-CoV-2 spike antibody response more than 10 days after the second mRNA vaccine dose. The patients actively receiving MM treatment, especially on regimens containing anti-CD38 and anti-BCMA, have lower antibody responses compared to healthy controls. Thus, it is of critical importance to monitor this patient population for serological responses. Non-responders may benefit from ongoing public health measures and from urgent study of prophylactic treatments to prevent SARS-CoV-2 infection.
Subject(s)
Severe Acute Respiratory Syndrome , Breakthrough Pain , COVID-19 , Multiple MyelomaABSTRACT
The pandemic, Covid-19, offered new opportunities for coercive online shopping to Indian consumers. Non techno-savvy and less educated consumers have also switched to online shopping. The present study investigates the customers' switching Behavior during the Covid-19 outbreak due to two attributes, perceived risks of infectious disease and the benefits of online shopping. Purchase and consumption acted as moderators in the model. A systematic empirical study with scientific research design was executed during March to August 2020 when the Covid-19 outbreak peaked, and online shopping became an alternate savior for continuity of life. This was the period when sanitization and mask-wearing, social distancing, avoiding touch was made compulsory. The hierarchical regression determined the catalyst role of Covid-19 in behavior switch and perception modification of online consumers. Findings suggest the change in risk perception during the Covid-19 pandemic lead to a change in marketing policies focused on awareness building. Control variables in the model behaved differently in online shopping, and new behaviors are expected to continue even after the pandemic. This study will contribute to elucidate switching buying behavior and the growth of the online business.
ABSTRACT
In this study we profiled vaccine-induced polyclonal antibodies as well as plasmablast derived mAbs from subjects who received SARS-CoV-2 spike mRNA vaccine. Polyclonal antibody responses in vaccinees were robust and comparable to or exceeded those seen after natural infection. However, that the ratio of binding to neutralizing antibodies after vaccination was greater than that after natural infection and, at the monoclonal level, we found that the majority of vaccine-induced antibodies did not have neutralizing activity. We also found a co-dominance of mAbs targeting the NTD and RBD of SARS-CoV-2 spike and an original antigenic-sin like backboost to seasonal human coronaviruses OC43 and HKU1 spike proteins. Neutralizing activity of NTD mAbs but not RBD mAbs against a clinical viral isolate carrying E484K as well as extensive changes in the NTD was abolished, suggesting that a proportion of vaccine induced RBD binding antibodies may provide substantial protection against viral variants carrying E484K.
Subject(s)
Neural Tube Defects , Severe Acute Respiratory SyndromeABSTRACT
An important question is arising as COVID-19 vaccines are getting rolled out: Should individuals who already had a SARS-CoV-2 infection receive one or two shots of the currently authorized mRNA vaccines. In this short report, we show that the antibody response to the first vaccine dose in individuals with pre-existing immunity is equal to or even exceeds the titers found in naive individuals after the second dose. We also show that the reactogenicity is significantly higher in individuals who have been infected with SARS-CoV-2 in the past. Changing the policy to give these individuals only one dose of vaccine would not negatively impact on their antibody titers, spare them from unnecessary pain and free up many urgently needed vaccine doses.