ABSTRACT
Background: Durability of SARS-CoV-2 Spike antibody responses after infection provides information relevant to understanding protection against COVID-19 in humans. We report the results of a follow-up evaluation of anti-SARS-CoV-2 antibodies in 23 convalescent patients with a median follow-up of 14 months (range 12.4-15.4) post first symptom onset.Findings: We found persistence of antibodies for all four specificities tested [Spike, Spike Receptor Binding Domain (Spike-RBD), Nucleocapsid, Nucleocapsid RNA Binding Domain (N-RBD)]. Anti-Spike antibodies persist at higher levels than anti-Nucleocapsid antibodies. The durability analysis supports a bi-phasic antibody decay with longer half-lives of antibodies after 6 months and antibody persistence for up to 14 months. Patients infected with the Wuhan (WA1) strain maintained strong cross-reactive recognition of Alpha and Delta Spike-RBD but significantly reduced binding to Beta and Mu Spike-RBD. Sixty percent of convalescent patients with detectable WA1-specific NAb also showed strong neutralization of the Delta variant. These data show that convalescent patients maintain functional antibody responses for more than one year after infection. One patient from this cohort showed strong increase of both Spike and Nucleocapsid antibodies at 14 months postinfection with robust cross-reactive antibodies and neutralization of a panel of Spike variants including Beta and Gamma, suggesting SARS-CoV-2 re-exposure. This patient provides an example of anti-Spike immunity able to control infection to asymptomatic level.Interpretations: The antibodies from SARS-CoV-2 convalescent patients persist over 14 months and continue to maintain cross-reactivity and strong functional properties.Trial Registration: This study included plasma donors who participated in a phase 2 study (NCT04408209 and NCT04743388)Funding: This work was supported by funds from the Intramural Research Program, National Institutes of Health, National Cancer Institute, Center for Cancer Research to G.N.P. and B.K.F. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.Declaration of Interest: The authors have declared that no conflict of interest exists.Ethical Approval: The study was approved by the local ethics committees of all participating hospitals.
Subject(s)
COVID-19 , NeoplasmsABSTRACT
The speed of development, versatility and efficacy of mRNA-based vaccines have been amply demonstrated in the case of SARS-CoV-2. DNA vaccines represent an important alternative since they induce both humoral and cellular immune responses in animal models and in human trials. We tested the immunogenicity and protective efficacy of DNA-based vaccine regimens expressing different prefusion-stabilized SARS-CoV-2 Spike antigens upon intramuscular injection followed by electroporation in rhesus macaques. Different Spike DNA vaccine regimens induced antibodies that potently neutralized SARS-CoV-2 in vitro and elicited robust T cell responses. The DNA-only vaccine regimens were compared to a regimen that included co- immunization of Spike DNA and protein in the same anatomical site, the latter of which showed significant higher antibody responses. All vaccine regimens led to control of SARS-CoV-2 intranasal/intratracheal challenge and absence of virus dissemination to the lower respiratory tract. Vaccine-induced binding and neutralizing antibody titers and antibody-dependent cellular phagocytosis inversely correlated with transient virus levels in the nasal mucosa. Importantly, the Spike DNA+Protein co-immunization regimen induced the highest binding and neutralizing antibodies and showed the strongest control against SARS-CoV-2 challenge in rhesus macaques. Author summaryAnti-Spike neutralizing antibodies provide strong protection against SARS-CoV-2 infection in animal models, and correlate with protection in humans, supporting the notion that induction of strong humoral immunity is key to protection. We show induction of robust antibody and T cell responses by different Spike DNA-based vaccine regimens able to effectively mediate protection and to control SARS-CoV-2 infection in the rhesus macaque model. This study provides the opportunity to compare vaccines able to induce different humoral and cellular immune responses in an effort to develop durable immunity against the SARS-CoV-2. A vaccine regimen comprising simultaneous co-immunization of DNA and Protein at the same anatomical site showed best neutralizing abilities and was more effective than DNA alone in inducing protective immune responses and controlling SARS-CoV-2 infection. Thus, an expansion of the DNA vaccine regimen to include co-immunization with Spike protein may be of advantage also for SARS-CoV-2.
Subject(s)
COVID-19ABSTRACT
BackgroundDiagnostic tests for SARS-CoV-2 infection (mostly RT-PCR and Computed Tomography) are not widely available in numerous countries, expensive and with imperfect performance MethodsThis multicenter retrospective study aimed to determine a pre-test probability score for SARS-CoV-2 infection based on clinical and biological variables. Patients were recruited from emergency and infectious disease departments and were divided into a training and a validation cohort. Demographic characteristics, clinical symptoms, and results of blood tests (complete white blood cell count, serum electrolytes and CRP) were collected. The pre-test probability score was derived from univariate analyses between patients and controls, followed by multivariate binary logistic analysis to determine the independent variables associated with SARS-CoV-2 infection. Points were assigned to each variable to create the PARIS score. ROC curve analysis determined the area under the curve (AUC). FindingsOne hundred subjects with clinical suspicion of SARS-CoV-2 infection were included in the training cohort, and 300 other consecutive individuals were included in the validation cohort. Low lymphocyte (<1{middle dot}3 G/L), eosinophil (<0{middle dot}06G/L), basophil (<0{middle dot}04G/L) and neutrophil counts (<5G/L) were associated with a high probability of SARS-CoV-2 infection. No clinical variable was statistically significant. The score had a good performance in the validation cohort (AUC=0.889 (CI: [0.846-0.932]; STD=0.022) with a sensitivity and Positive Predictive Value of high-probability score of 80{middle dot}3% and 92{middle dot}3% respectively. Furthermore, a low-probability score excluded SARS-CoV-2 infection with a Negative Predictive Value of 99.5%. InterpretationThe PARIS score based on complete white blood cell count has a good performance to categorize the pre-test probability of SARS-CoV-2 infection. It could help clinicians avoid diagnostic tests in patients with a low-probability score and conversely keep on testing individuals with high-probability score but negative RT-PCR or CT. It could prove helpful in countries with a low-availability of PCR and/or CT during the current period of pandemic. FundingNone Putting research into contextO_ST_ABSEvidence before this studyC_ST_ABSIn numerous countries, large population testing is impossible due to the limited availability and costs of RT-PCR kits and CT-scan. Furthermore, false-negativity of PCR or CT as well as COVID-19 pneumonia mimickers on CT may lead to inaccurate diagnoses. Pre-test probability combining clinical and biological features has proven to be a particularly useful tool, already used in clinical practice for management of patients with a suspicion of pulmonary embolism. Added value of this studyThis retrospective study including 400 patients with clinical suspicion of SARS-CoV-2 infection was composed of a training and a validation cohort. The pre-test probability score (PARIS score) determines 3 levels of probability of SARS-CoV2 infection based on white blood cell count (lymphocyte, eosinophil, basophil and neutrophil cell count). Implications of the available evidenceThis pre-test probability may help to adapt SARS-CoV-2 infection diagnostic tests. The high negative predictive value (99{middle dot}5%) of the low probability category may help avoid further tests, especially during a pandemic with overwhelmed resources. A high probability score combined with typical CT features can be considered sufficient for diagnosis confirmation.