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1.
ssrn; 2021.
Preprint in English | PREPRINT-SSRN | ID: ppzbmed-10.2139.ssrn.3940264

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 , Neoplasms
2.
biorxiv; 2021.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2021.06.11.448032

ABSTRACT

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-19
3.
ssrn; 2021.
Preprint in English | PREPRINT-SSRN | ID: ppzbmed-10.2139.ssrn.3832995

ABSTRACT

Early responses to vaccination are important in shaping both humoral and cellular protective immunity. Dissecting innate vaccine signatures may predict immunogenicity and help optimizing efficacy of mRNA and other vaccine strategies. We characterized the cytokine and chemokine responses to the 1st and 2nd dose of the BNT162b2 mRNA (Pfizer/BioNtech) vaccine in antigen-naïve vaccine recipients and individuals previously infected by COVID-19 (NCT04743388). Transient increases in IL-15 and IFN-γ levels early after boost correlated with Spike-RBD antibody levels, supporting their possible use as biomarkers of successful vaccination. We identified a systemic signature including IL-15, IFN-γ and IP-10/CXCL10 increase after the 1st vaccination, which was enriched by TNF-α and IL-6 after the 2nd vaccination. In vaccine recipients with history of COVID-19 infection, a single vaccine dose resulted in both strong cytokine induction and antibody titers similar to the ones observed upon booster vaccination in antigen-naïve individuals, a result with potential implication for future public health recommendations.Funding Information: Funding: This research was supported [in part] by the IntramuralResearch Program of the NIH, NCI to G.N.P. and B.K.F.Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: All study procedures were carried out in accordance with the declaration of Helsinki (18th World Medical Association Assembly), its subsequent amendments, the Greek regulations and guidelines, as well as the good clinical practice guidelines (GCP) as defined by the International Conference of Harmonization. The study was also approved by the local ethic committee of Alexandra General Hospital (no 15/23 December 2020).


Subject(s)
COVID-19
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