Project description:In vitro determination of severe acute respiratory syndrome coronavirus 2 neutralizing antibodies induced in serum samples from recipients of the CoronaVac vaccine showed a short protection period against the original virus strain and limited protection against variants of concern. These data provide support for vaccine boosters, especially variants of concern circulate.
Project description:The COVID-19 pandemic urgently needs therapeutic and prophylactic interventions. Here we report the rapid identification of SARS-CoV-2 neutralizing antibodies by high-throughput single-cell RNA and VDJ sequencing of antigen-enriched B cells from 60 convalescent patients.
Project description:BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible of the current pandemic ongoing all around the world. Since its discovery in 2019, several circulating variants have emerged and some of them are associated with increased infections and death rate. Despite the genetic differences among these variants, vaccines approved for human use have shown a good immunogenic and protective response against them. In Chile, over 70% of the vaccinated population is immunized with CoronaVac, an inactivated SARS-CoV-2 vaccine. The immune response elicited by this vaccine has been described against the first SARS-CoV-2 strain isolated from Wuhan, China and the D614G strain (lineage B). To date, four SARS-CoV-2 variants of concern described have circulated worldwide. Here, we describe the neutralizing capacities of antibodies secreted by volunteers in the Chilean population immunized with CoronaVac against variants of concern Alpha (B.1.1.7), Beta (B.1.351) Gamma (P.1) and Delta (B.617.2).MethodsVolunteers enrolled in a phase 3 clinical trial were vaccinated with two doses of CoronaVac in 0-14 or 0-28 immunization schedules. Sera samples were used to evaluate the capacity of antibodies induced by the vaccine to block the binding between Receptor Binding Domain (RBD) from variants of concern and the human ACE2 receptor by an in-house ELISA. Further, conventional microneutralization assays were used to test neutralization of SARS-CoV-2 infection. Moreover, interferon-γ-secreting T cells against Spike from variants of concern were evaluated in PBMCs from vaccinated subjects using ELISPOT.ResultsCoronaVac promotes the secretion of antibodies able to block the RBD of all the SARS-CoV-2 variants studied. Seropositivity rates of neutralizing antibodies in the population evaluated were over 97% for the lineage B strain, over 80% for Alpha and Gamma variants, over 75% for Delta variant and over 60% for the Beta variant. Geometric means titers of blocking antibodies were reduced when tested against SARS-CoV-2 variants as compared to ancestral strain. We also observed that antibodies from vaccinated subjects were able to neutralize the infection of variants D614G, Alpha, Gamma and Delta in a conventional microneutralization assay. Importantly, after SARS-CoV-2 infection, we observed that the blocking capacity of antibodies from vaccinated volunteers increased up to ten times for all the variants tested. We compared the number of interferon-γ-secreting T cells specific for SARS-CoV-2 Spike WT and variants of concern from vaccinated subjects and we did not detect significant differences.ConclusionImmunization with CoronaVac in either immunization schedule promotes the secretion of antibodies able to block SARS-CoV-2 variants of concern and partially neutralizes SARS-CoV-2 infection. In addition, it stimulates cellular responses against all variants of concern.
Project description:The only severe acute respiratory syndrome (SARS) vaccine currently being tested in clinical trial consists of inactivated severe acute respiratory syndrome-associate coronavirus (SARS-CoV). However, limited information is available about host immune responses induced by the inactivated SARS vaccine. In this study, we demonstrated that SARS-CoV inactivated by beta-propiolactone elicited high titers of antibodies in the immunized mice and rabbits that recognize the spike (S) protein, especially the receptor-binding domain (RBD) in the S1 region. The antisera from the immunized animals efficiently bound to the RBD and blocked binding of RBD to angiotensin-converting enzyme 2, the functional receptor on the susceptible cells for SARS-CoV. With a sensitive and quantitative single-cycle infection assay using pseudovirus bearing the SARS-CoV S protein, we demonstrated that mouse and rabbit antisera significantly inhibited S protein-mediated virus entry with mean 50% inhibitory titers of 1:7393 and 1:2060, respectively. These data suggest that the RBD of S protein is a major neutralization determinant in the inactivated SARS vaccine which can induce potent neutralizing antibodies to block SARS-CoV entry. However, caution should be taken in using the inactivated SARS-CoV as a vaccine since it may also cause harmful immune and/or inflammatory responses.
Project description:The recently emerged coronavirus SARS-CoV-2, the causative agent of COVID-19, is rapidly spreading in the world. The exponentially expanding threat of SARS-CoV-2 to global health highlights the urgent need for a vaccine. Herein we show the rapid development of a novel, highly efficient, and safe COVID-19 vaccine using a rabies virus-based vector that has proven to be an efficient vaccine against several emerging infectious diseases. This study reports that both a live and an inactivated rabies virus containing the SARS-CoV-2 spike S1 protein induces potent virus-neutralizing antibodies at much higher levels than seen in the sera of convalescent patients. In summary, the results provided here warrant further development of this safe and established vaccine platform against COVID-19.
Project description:The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits reduced susceptibility to vaccine-induced neutralizing antibodies, requiring a boost to generate protective immunity. We assess the magnitude and short-term durability of neutralizing antibodies after homologous and heterologous boosting with mRNA and Ad26.COV2.S vaccines. All prime-boost combinations substantially increase the neutralization titers to Omicron, although the boosted titers decline rapidly within 2 months from the peak response compared with boosted titers against the prototypic D614G variant. Boosted Omicron neutralization titers are substantially higher for homologous mRNA vaccine boosting, and for heterologous mRNA and Ad26.COV2.S vaccine boosting, compared with homologous Ad26.COV2.S boosting. Homologous mRNA vaccine boosting generates nearly equivalent neutralizing activity against Omicron sublineages BA.1, BA.2, and BA.3 but modestly reduced neutralizing activity against BA.2.12.1 and BA.4/BA.5 compared with BA.1. These results have implications for boosting requirements to protect against Omicron and future variants of SARS-CoV-2. This trial was conducted under ClincalTrials.gov: NCT04889209.
Project description:Dysregulated immune responses contribute to the excessive and uncontrolled inflammation observed in severe COVID-19. However, how immunity to SARS-CoV-2 is induced and regulated remains unclear. Here we uncover a role of the complement system in the induction of innate and adaptive immunity to SARS-CoV-2. Complement rapidly opsonizes SARS-CoV-2 particles via the lectin pathway. Complement-opsonized SARS-CoV-2 efficiently induces type-I interferon and pro-inflammatory cytokine responses via activation of dendritic cells, which are inhibited by antibodies against the complement receptors (CR) 3 and 4. Serum from COVID-19 patients, or monoclonal antibodies against SARS-CoV-2, attenuate innate and adaptive immunity induced by complement-opsonized SARS-CoV-2. Blocking of CD32, the FcγRII antibody receptor of dendritic cells, restores complement-induced immunity. These results suggest that opsonization of SARS-CoV-2 by complement is involved in the induction of innate and adaptive immunity to SARS-CoV-2 in the acute phase of infection. Subsequent antibody responses limit inflammation and restore immune homeostasis. These findings suggest that dysregulation of the complement system and FcγRII signaling may contribute to severe COVID-19.
Project description:Air pollution is a critical risk factor for the prevalence of COVID-19. However, few studies have focused on whether air pollution affects the efficacy of the SARS-CoV-2 vaccine. To better guide the knowledge surrounding this vaccination, we conducted a cross-section study to identify the relationships between air pollutant exposure and plasma neutralizing antibody (NAb) titers of an inactivated SARS-CoV-2 vaccine (Vero cell, CoronaVac, SINOVΛC, China). We recruited 239 healthcare workers aged 21-50 years who worked at Suining Central Hospital. Of these, 207 were included in this study, depending on vaccination date. The data regarding air pollutants were collected to calculate individual daily exposure dose (DED). The geometric mean of all six pollutant DEDs was applied to estimate the combined toxic effects (DEDcomplex). Then, the participants were divided into two groups based on the mean value of DEDcomplex. The median plasma NAb titer was 12.81 AU/mL, with 85.99% vaccine efficacy in healthcare workers against SARS-CoV-2. In exposure group, observations included lower plasma NAb titers (median: 11.13 AU/mL vs. 14.56 AU/mL), more peripheral counts of white blood cells and monocytes (mean: 6.71 × 109/L vs. 6.29 × 109/L and 0.49 × 109/L vs. 0.40 × 109/L, respectively), and a higher peripheral monocyte ratio (7.38% vs. 6.50%) as compared to the reference group. In addition, elevated air pollutant DEDs were associated with decreased plasma NAb titers. To our knowledge, this study is the first to report the relationship between air pollutant exposure and plasma NAb titers of the SARS-CoV-2 vaccine. This suggests that long-term exposure to air pollutants may inhibit plasma NAb expression by inducing chronic inflammation. Therefore, to achieve early herd immunity and hopefully curb the COVID-19 epidemic, vaccinations should be administered promptly to those eligible, and environmental factors should be considered as well.
Project description:Several variants of SARS-CoV-2 have emerged. Those with mutations in the angiotensin-converting enzyme (ACE2) receptor binding domain (RBD) are associated with increased transmission and severity. In this study, we developed both antibody quantification and functional neutralization assays. Analyses of both COVID-19 convalescent and diagnostic cohorts strongly support the use of RBD antibody levels as an excellent surrogate to biochemical neutralization activities. Data further revealed that the samples from mRNA vaccinated individuals had a median of 17 times higher RBD antibody levels and a similar degree of increased neutralization activities against RBD-ACE2 binding than those from natural infections. Our data showed that N501Y RBD had fivefold higher ACE2 binding than the original variant. While some antisera from naturally infected subjects had substantially reduced neutralization ability against N501Y RBD, all blood samples from vaccinated individuals were highly effective in neutralizing it. Thus, our data indicates that mRNA vaccination may generate more neutralizing RBD antibodies than natural immunity. It further suggests a potential need to maintain high RBD antibody levels to control the more infectious SARS-CoV-2 variants.