Status of Humoral and Cellular Immune Responses within 12 Months following CoronaVac Vaccination against COVID-19.

Understanding immune memory to COVID-19 vaccines is critical for the design and optimal vaccination schedule for curbing the COVID-19 pandemic. Here, we assessed the status of humoral and cellular immune responses at 1, 3, 6, and 12 months after two-dose CoronaVac vaccination. A total of 150 participants were enrolled, and 136 of them completed the study through the 12-month endpoint. Our results show that, at 1 month after vaccination, both binding and neutralizing antibodies could be detected; the seropositive rate of binding antibodies and seroconversion rate of neutralizing antibodies were 99% and 50%, respectively. From 3 to 12 months, the binding and neutralizing antibodies declined over time. At 12 months, the binding and neutralizing antibodies were still detectable and significantly higher than the baseline. Gamma interferon (IFN-γ) and interleukin 2 (IL-2) secretion specifically induced by the receptor-binding domain (RBD) persisted at high levels until 6 months and could be observed at 12 months, while the levels of IL-5 and granzyme B (GzmB) were hardly detected, demonstrating a Th1-biased response. In addition, specific CD4+ T central memory (TCM), CD4+ effector memory (TEM), CD8+ TEM, and CD8+ terminal effector (TE) cells were all detectable and functional up to 12 months after the second dose, as the cells produced IFN-γ, IL-2, and GzmB in response to stimulation of SARS-CoV-2 RBD. Our work provides evidence that CoronaVac induced not only detectable binding and neutralizing antibody responses, but also functional SARS-CoV-2-specific CD4+ and CD8+ memory T cells for up to 12 months. IMPORTANCE CoronaVac is an inactivated vaccine containing whole-virion SARS-CoV-2, which has been approved in 43 countries for emergency use as of 26 November 2021. However, the long-term immune persistence of the CoronaVac vaccine is still unknown. Here, we reported the status of the persistence of antibodies and cellular responses within 12 months after two doses of CoronaVac. Such data are crucial to inform ongoing and future vaccination strategies to combat COVID-19.

Evaluation of Immunogenicity by Pseudovirus Neutralization Assays for SARS-CoV-2 Variants after Primary and Booster Immunization.

OBJECTIVES: To determine the status of immune responses after primary and booster immunization for SARS-CoV-2 variants and evaluate the differences in disease resistance based upon titers of neutralizing antibodies (NAbs) against the variants. METHODS: Participants aged 18-59 years received 2 doses of inactivated COVID-19 vaccine, 14 days apart, and a booster dose after 12 months. Blood samples were collected before vaccination (baseline), 1 and 6 months after primary immunization, and at multiple instances within 21 days of the booster dose. NAbs against the spike protein of Wuhan-Hu-1 and 3 variants were measured using pseudovirus neutralization assays. RESULTS: Of 400 enrolled participants, 387 completed visits scheduled within 6 months of the second dose and 346 participants received the booster dose in the follow-up research. After 1 month of primary immunization, geometric mean titers (GMTs) of NAbs peaked for Wuhan-Hu-1, whereas GMTs of other variants were <30. After 6 months of primary immunization, GMTs of NAbs against all strains were <30. After 3 days of booster immunization, GMTs were unaltered, seroconversion rates reached approximately 50% after 7 days, and GMTs of NAbs against all strains peaked at 14 days. CONCLUSION: Two-dose of inactivated COVID-19 vaccine induced the formation of NAbs and memory-associated immune responses, and high titers of NAbs against the variants obtained after booster immunization may further improve the effectiveness of the vaccine.

A non-ACE2 competing human single-domain antibody confers broad neutralization against SARS-CoV-2 and circulating variants.

The current COVID-19 pandemic has heavily burdened the global public health system and may keep simmering for years. The frequent emergence of immune escape variants have spurred the search for prophylactic vaccines and therapeutic antibodies that confer broad protection against SARS-CoV-2 variants. Here we show that the bivalency of an affinity maturated fully human single-domain antibody (n3113.1-Fc) exhibits exquisite neutralizing potency against SARS-CoV-2 pseudovirus, and confers effective prophylactic and therapeutic protection against authentic SARS-CoV-2 in the host cell receptor angiotensin-converting enzyme 2 (ACE2) humanized mice. The crystal structure of n3113 in complex with the receptor-binding domain (RBD) of SARS-CoV-2, combined with the cryo-EM structures of n3113 and spike ecto-domain, reveals that n3113 binds to the side surface of up-state RBD with no competition with ACE2. The binding of n3113 to this novel epitope stabilizes spike in up-state conformations but inhibits SARS-CoV-2 S mediated membrane fusion, expanding our recognition of neutralization by antibodies against SARS-CoV-2. Binding assay and pseudovirus neutralization assay show no evasion of recently prevalent SARS-CoV-2 lineages, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) for n3113.1-Fc with Y58L mutation, demonstrating the potential of n3113.1-Fc (Y58L) as a promising candidate for clinical development to treat COVID-19.

"Fei Yan No. 1" as a Combined Treatment for COVID-19: An Efficacy and Potential Mechanistic Study.

There has been a large global outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), representing a major public health issue. In China, combination therapy, including traditional Chinese medicine (TCM) as a treatment for COVID-19 has been used widely. "Fei Yan No. 1" (QFDYG) is a formula recommended by the Hubei Government to treat COVID-19. A retrospective study of 84 COVID-19 patients from Hubei Provincial Hospital of TCM and Renmin Hospital of Hanchuan was conducted to explore the clinical efficacy of QFDYG combination therapy. TCMSP and YaTCM databases were used to determine the components of all Chinese herbs in QFDYG. Oral bioavailability (OB) ≥ 30% and drug-like (DL) quality ≥ 0.18 were selected as criteria for screening the active compounds identified within the TCMSP database. The targets of active components in QFDYG were determined using the Swiss TargetPrediction (SIB) and Targetnet databases. The STRING database and the Network Analyzer plugin in Cytoscape were used to obtain protein-protein interaction (PPI) network topology parameters and to identify hub targets. Gene Ontology (GO) enrichment was conducted using FunRich version 3.1.3, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment using ClueGO version 2.5.6 software. PPI and compound-pathway (C-T) networks were constructed using Cytoscape 3.6.0. Compared with the control group, combined treatment with QFDYG resulted in a significantly higher rate of patients recovering from symptoms and shorter the time. After 14 days of treatment, QFDYG combined treatment increased the proportion of patients testing negative for SARS-CoV-2 nucleic acid by RT-PCR. Compared with the control group, promoting focal absorption and inflammation as viewed on CT images. GO and KEGG pathway enrichment indicated that QFDYG principally regulated biological processes, such as inflammation, an immune response, and apoptosis. The present study revealed that QFDYG combination therapy offered particular therapeutic advantages, indicating that the theoretical basis for the treatment of COVID-19 by QFDYG may play an antiviral and immune response regulation through multiple components, targets, and pathways, providing reference for the clinical treatment of COVID-19.