Subject(s)
Antibodies, Neutralizing , Antibodies, Neutralizing/immunology , Humans , Vaccines, Synthetic/immunology , Vaccines, Synthetic/genetics , Immunization, Secondary , Recombinant Proteins/immunology , Recombinant Proteins/genetics , SARS-CoV-2/immunology , SARS-CoV-2/genetics , Animals , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/prevention & controlABSTRACT
OBJECTIVE: To investigate the effects of repeated vaccination with ancestral SARS-CoV-2 (Wuhan-hu-1)-based inactivated, recombinant protein subunit or vector-based vaccines on the neutralizing antibody response to Omicron subvariants. METHODS: Individuals who received four-dose vaccinations with the Wuhan-hu-1 strain, individuals who were infected with the BA.5 variant alone without prior vaccination, and individuals who experienced a BA.5 breakthrough infection following receiving 2-4 doses of the Wuhan-hu-1 vaccine were enrolled. Neutralizing antibodies against D614G, BA.5, XBB.1.5, EG.5.1, and BA.2.86 were detected using a pseudovirus-based neutralization assay. Antigenic cartography was used to analyze cross-reactivity patterns among D614G, BA.5, XBB.1.5, EG.5.1, and BA.2.86 and sera from individuals. RESULTS: The highest neutralizing antibody titers against D614G were observed in individuals who only received four-dose vaccination and those who experienced BA.5 breakthrough infection, which was also significantly higher than the antibody titers against XBB.1.5, EG.5.1, and BA.2.86. In contrast, only BA.5 infection elicited comparable neutralizing antibody titers against the tested variants. While neutralizing antibody titers against D614G or BA.5 were similar across the cohorts, the neutralizing capacity of antibodies against XBB.1.5, EG.5.1, and BA.2.86 was significantly reduced. BA.5 breakthrough infection following heterologous booster induced significantly higher neutralizing antibody titers against the variants, particularly against XBB.1.5 and EG.5.1, than uninfected vaccinated individuals, only BA.5 infected individuals, or those with BA.5 breakthrough infection after primary vaccination. CONCLUSIONS: Our findings suggest that repeated vaccination with the Wuhan-hu-1 strain imprinted a neutralizing antibody response toward the Wuhan-hu-1 strain with limited effects on the antibody response to the Omicron subvariants.
ABSTRACT
The ongoing emergence of SARS-CoV-2 variants poses challenges to the immunity induced by infections and vaccination. We conduct a 6-month longitudinal evaluation of antibody binding and neutralization of sera from individuals with six different combinations of vaccination and infection against BA.5, XBB.1.5, EG.5.1, and BA.2.86. We find that most individuals produce spike-binding IgG or neutralizing antibodies against BA.5, XBB.1.5, EG.5.1, and BA.2.86 2 months after infection or vaccination. However, compared to ancestral strain and BA.5 variant, XBB.1.5, EG.5.1, and BA.2.86 exhibit comparable but significant immune evasion. The spike-binding IgG and neutralizing antibody titers decrease in individuals without additional antigen exposure, and <50% of individuals neutralize XBB.1.5, EG.5.1, and BA.2.86 during the 6-month follow-up. Approximately 57% of the 107 followed up individuals experienced an additional infection, leading to improved binding IgG and neutralizing antibody levels against these variants. These findings provide insights into the impact of SARS-CoV-2 variants on immunity following repeated exposure.
Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , COVID-19 , Immunoglobulin G , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccination , Humans , SARS-CoV-2/immunology , COVID-19/immunology , COVID-19/prevention & control , COVID-19/virology , Antibodies, Viral/immunology , Antibodies, Viral/blood , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/blood , COVID-19 Vaccines/immunology , Immunoglobulin G/immunology , Immunoglobulin G/blood , Spike Glycoprotein, Coronavirus/immunology , Female , Male , Adult , Middle Aged , Antibody Formation/immunologyABSTRACT
Booster immunizations and breakthrough infections can elicit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant neutralizing activity. However, the durability of the neutralization response is unknown. We characterize the sensitivity of BA.1, BA.2, BA.2.75, BA.4/BA.5, BF.7, BQ.1.1, and XBB against neutralizing antibodies from vaccination, hybrid immunity, and breakthrough infections 4-6 months after vaccination and infection. We show that a two-dose CoronaVac or a third-dose ZF2001 booster elicits limited neutralization against Omicron subvariants 6 months after vaccination. Hybrid immunity as well as Delta, BA.1, and BA.2 breakthrough infections induce long-term persistence of the antibody response, and over 70% of sera neutralize BA.1, BA.2, BA.4/BA.5, and BF.7. However, BQ.1.1 and XBB, followed by BA.2.75, are more resistant to neutralization, with neutralizing titer reductions of â¼9- to 41-fold, â¼16- to 63-fold, and â¼4- to 25-fold, respectively. These data highlight additional vaccination in CoronaVac- or ZF2001-vaccinated individuals and provide insight into the durability of neutralization against Omicron subvariants.
Subject(s)
Breakthrough Infections , COVID-19 , Humans , COVID-19/prevention & control , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, ViralABSTRACT
BACKGROUND: The emergence of SARS-CoV-2 Omicron subvariants has raised questions regarding resistance to immunity by natural infection or immunization. We examined the sensitivity of Delta and Omicron subvariants (BA.1, BA.1.1, BA.2, BA.2.12.1, BA.4/5, and BA.3) to neutralizing antibodies from BBIBP-CorV-vaccinated and BBIBP-CorV- or ZF2001-boosted individuals, as well as individuals with Delta and BA.1 breakthrough infections, and determined their fusogenicity and infectivity. METHODS: In this cross-sectional study, serum samples from two doses of BBIBP-CorV-vaccinated individuals 1 (n = 36), 3 (n = 36), and 7 (n = 37) months after the second dose; BBIBP-CorV- (n = 25) or ZF2001-boosted (n = 30) individuals; and fully vaccinated individuals with Delta (n = 30) or BA.1 (n = 26) infection were collected. The serum-neutralizing reactivity and potency of bebtelovimab were assessed against D614G, Delta, and Omicron subvariants (BA.1, BA.1.1, BA.2, BA.2.12.1, BA.4/5, and BA.3) through a pseudovirus neutralization assay. The fusogenicity and infectivity of D614G, Delta, and Omicron subvariants were determined by cell-cell fusion assay and pseudovirus infection assay, respectively. RESULTS: Omicron subvariants markedly escaped vaccine-elicited neutralizing antibodies after two doses of BBIBP-CorV with comparable efficiency. A third dose vaccination of BBIBP-CorV or ZF2001 increased neutralizing antibody titers and breadth against Delta and three Omicron subvariants. Delta and BA.1 breakthrough infections induced comparable neutralizing antibody titers against D614G and Delta variants, whereas BA.1 breakthrough infections elicited a stronger and broader antibody response against three Omicron subvariants than Delta breakthrough infections. BA.2.12.1 and BA.4/5 are more resistant to immunity induced by breakthrough infections. Bebtelovimab had no significant loss of potency against the Delta and Omicron subvariants. Cell culture experiments showed Omicron subvariants to be less fusogenic and have higher infectivity than D614G and Delta with comparable efficiency. CONCLUSIONS: These findings have important public health implications and highlight the importance of repeated exposure to SARS-CoV-2 antigens to broaden the neutralizing antibody response against Omicron subvariants.
Subject(s)
COVID-19 , Humans , Cross-Sectional Studies , SARS-CoV-2 , Antibodies, Neutralizing , Breakthrough Infections , Antibodies, ViralABSTRACT
BACKGROUND: Pigs are unique reservoirs for virus ecology. Despite the increased use of improved biosecurity measures, pig viruses readily circulate in Chinese swine farms. OBJECTIVES: The main objective of this study was to examine archived swine oral secretion samples with a panel of pan-species viral assays such that we might better describe the viral ecology of swine endemic viruses in Chinese farms. METHODOLOGY: Two hundred (n = 200) swine oral secretion samples, collected during 2015 and 2016 from healthy pigs on six swine farms in two provinces in China, were screened with molecular pan-species assays for coronaviruses (CoVs), adenoviruses (AdVs), enteroviruses (EVs), and paramyxoviruses (PMV). Samples were also screened for porcine circovirus (PCV) 3, porcine reproductive and respiratory syndrome virus (PRRSV) and influenza A virus (IAV). RESULTS: Among 200 swine oral secretion samples, 152 (76.0%) were found to have at least one viral detection. Thirty-four samples (17%) were positive for more than one virus, including 24 (70.5%) with dual detection and 10 (29.5%) with triple detection. Seventy-eight (39.0%) samples were positive for porcine AdVs, 22 (11.0%) were positive for porcine CoVs, 21 (10.5%) were positive for IAVs, 13 (6.5%) were positive for PCV, 7 (3.5%) were positive for PMV, six (3.0%) were positive for PRRSV and five (2.5%) were positive for porcine EV. CONCLUSION: Our findings underscore the high prevalence of numerous viruses among production pigs in China and highlight the need for routine, periodic surveillance for novel virus emergence with the goal of protecting pigs.
Subject(s)
Circovirus , Influenza A virus , Porcine Reproductive and Respiratory Syndrome , Porcine respiratory and reproductive syndrome virus , Swine Diseases , Animals , Porcine Reproductive and Respiratory Syndrome/epidemiology , SwineABSTRACT
The severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) survivors are more likely to produce a potent immune response to SARS-CoV-2 after booster vaccination. We assessed humoral and T cell responses against SARS-CoV-2 in previously vaccinated SARS-CoV-1 survivors and naïve healthy individuals (NHIs) after a booster Ad5-nCoV dose. Boosted SARS-CoV-1 survivors had a high neutralization of SARS-CoV-2 Wuhan-Hu-1 (WA1), Beta, and Delta but is limited to Omicron subvariants (BA.1, BA.2, BA.2.12.1, and BA.4/BA.5). Most boosted SARS-CoV-1 survivors had robust SARS-CoV-2-specific CD4+ and CD8+ T cell responses. While booster vaccination in NHIs elicited less or ineffective neutralization of WA1, Beta, and Delta, and none of them induced neutralizing antibodies against Omicron subvariants. However, they developed comparable SARS-CoV-2-specific T cell responses compared to boosted SARS-CoV-1 survivors. These findings suggest that boosted Ad5-nCoV would not elicit effective neutralizing antibodies against Omicron subvariants in SARS-CoV-1 survivors and NHIs but induced comparable robust T cell responses. Achieving a high antibody titer in SARS-CoV-1 survivors and NHIs is desirable to generate broad neutralization.
Subject(s)
AIDS Vaccines , COVID-19 , Influenza Vaccines , Papillomavirus Vaccines , Respiratory Syncytial Virus Vaccines , SAIDS Vaccines , Antibodies, Neutralizing , Antibodies, Viral , BCG Vaccine , COVID-19 Vaccines , Diphtheria-Tetanus-Pertussis Vaccine , Humans , Measles-Mumps-Rubella Vaccine , SARS-CoV-2 , SurvivorsABSTRACT
The emergence of the SARS-CoV-2 Omicron BA.1 (B.1.1.529) variant has raised questions regarding resistance to neutralizing antibodies elicited by natural infection or immunization. We examined the neutralization activity of sera collected from previously SARS-CoV-2-infected individuals and SARS-CoV-2 naive individuals who received BBIBP-CorV or CoronaVac to BA.1 and the earlier variants Alpha, Beta, and Delta. Both sera from convalescent patients over three months after infection and two-dose BBIBP-CorV or CoronaVac vaccine recipients barely inhibited BA.1, less effectively neutralized Beta and Delta, and moderately neutralized Alpha. However, administering a single dose of BBIBP-CorV or CoronaVac in previously infected individuals or a third dose booster vaccination of BBIBP-CorV or CoronaVac in previously vaccinated individuals enhances neutralizing activity against BA.1 and other variants, albeit with a lower antibody titer for BA.1. Our data suggest that a booster vaccination is important to broaden neutralizing antibody responses against the variants.
ABSTRACT
Preexisting immunity cross-reactive to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in SARS-CoV-1 survivors suggests that a coronavirus disease 2019 vaccine may boost such preexisting cross-reactive memory T cells. We measure SARS-CoV-2 and SARS-CoV-1 spike-specific neutralizing antibody and T cell responses in a single dose of Ad5-nCoV-immunized SARS-CoV-1 survivors 6 months after vaccination. Compared with Ad5-nCoV-immunized naive healthy individuals (NHIs), vaccination of Ad5-nCoV in SARS-CoV-1 survivors boosts the antibody response against SARS-CoV-1 but induces a limited neutralizing antibody that is capable of neutralizing SARS-CoV-2 variants of concern, and nearly all serum samples lose neutralization to Omicron subvariants. Immunized SARS-CoV-1 survivors produce a T cell response to SARS-CoV-2 comparable with that of Ad5-nCoV-immunized NHIs. However, a robust cross-reactive T cell response to SARS-CoV-1 is identified in immunized SARS-CoV-1 survivors compared with Ad5-nCoV-immunized NHIs. These findings suggest that vaccination with Ad5-nCoV elicits a stronger neutralizing antibody and cross-reactive T cell responses against SARS-CoV-1 in SARS-CoV-1 survivors.
Subject(s)
COVID-19 , Viral Vaccines , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , Humans , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Survivors , VaccinationABSTRACT
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron (B.1.1.529) variant extensively escape neutralizing antibodies by vaccines or infection. We assessed serum neutralizing activity in sera from Delta infection after vaccination and Delta infection only against SARS-CoV-2 Wuhan-Hu-1 (WA1), Beta, Delta, and Omicron. Sera from Delta infection only could neutralize WA1 and Delta but almost completely lost capacity to neutralize Beta and Omicron. However, Delta infection after vaccination resulted in a significant increase of serum neutralizing activity against WA1, Beta, and Omicron. This study demonstrates that breakthrough infection of Delta substantially induced high potency humoral immune response against the Omicron variant and other emerged variants.
Subject(s)
Antibodies, Neutralizing , COVID-19 Vaccines , COVID-19 , Immunity, Humoral , Humans , Antibodies, Viral , COVID-19/immunology , COVID-19/prevention & control , Neutralization Tests , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccination , COVID-19 Vaccines/immunologySubject(s)
COVID-19/metabolism , Carrier State/metabolism , SARS-CoV-2/metabolism , Carrier State/virology , Female , Humans , MaleABSTRACT
While some individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) present mild-to-severe disease, many SARS-CoV-2-infected individuals are asymptomatic. We sought to identify the distinction of immune response between asymptomatic and moderate patients. We performed single-cell transcriptome and T-cell/B-cell receptor (TCR/BCR) sequencing in 37 longitudinal collected peripheral blood mononuclear cell samples from asymptomatic, moderate, and severe patients with healthy controls. Asymptomatic patients displayed increased CD56briCD16- natural killer (NK) cells and upregulation of interferon-gamma in effector CD4+ and CD8+ T cells and NK cells. They showed more robust TCR clonal expansion, especially in effector CD4+ T cells, but lack strong BCR clonal expansion compared to moderate patients. Moreover, asymptomatic patients have lower interferon-stimulated genes (ISGs) expression in general but large interpatient variability, whereas moderate patients showed various magnitude and temporal dynamics of the ISGs expression across multiple cell populations but lower than a patient with severe disease. Our data provide evidence of different immune signatures to SARS-CoV-2 in asymptomatic infections.
Subject(s)
COVID-19 , Carrier State/immunology , Lymphocytes/immunology , SARS-CoV-2/immunology , Single-Cell Analysis , Transcriptome/immunology , Adolescent , Adult , COVID-19/genetics , COVID-19/immunology , Female , Humans , Male , Middle Aged , Receptors, Antigen, B-Cell/genetics , Receptors, Antigen, B-Cell/immunology , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell/immunology , SARS-CoV-2/geneticsABSTRACT
We examined a collection of 386 animal, 451 human, and 109 archived bioaerosol samples with a new pan-species coronavirus molecular assay. Thirty-eight (4.02%) of 946 specimens yielded evidence of human or animal coronaviruses. Our findings demonstrate the utility of employing the pan-CoV RT-PCR assay in detecting varied coronavirus among human, animal, and environmental specimens. This RT-PCR assay might be employed as a screening diagnostic for early detection of coronaviruses incursions or prepandemic coronavirus emergence in animal or human populations.
ABSTRACT
BACKGROUND: The duration of humoral and T and B cell response after the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unclear. METHODS: We performed a cross-sectional study to assess the virus-specific antibody and memory T and B cell responses in coronavirus disease 2019 (COVID-19) patients up to 343 days after infection. Neutralizing antibodies and antibodies against the receptor-binding domain, spike, and nucleoprotein of SARS-CoV-2 were measured. Virus-specific memory T and B cell responses were analyzed. RESULTS: We enrolled 59 patients with COVID-19, including 38 moderate, 16 mild, and 5 asymptomatic patients; 31 (52.5%) were men and 28 (47.5%) were women. The median age was 41 years (interquartile range, 30-55). The median day from symptom onset to enrollment was 317 days (range 257 to 343 days). We found that approximately 90% of patients still have detectable immunoglobulin (Ig)G antibodies against spike and nucleocapsid proteins and neutralizing antibodies against pseudovirus, whereas ~60% of patients had detectable IgG antibodies against receptor-binding domain and surrogate virus-neutralizing antibodies. The SARS-CoV-2-specific IgG+ memory B cell and interferon-γ-secreting T cell responses were detectable in more than 70% of patients. CONCLUSIONS: Severe acute respiratory syndrome coronavirus 2-specific immune memory response persists in most patients approximately 1 year after infection, which provides a promising sign for prevention from reinfection and vaccination strategy.
Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Immunity, Cellular/immunology , Adult , B-Lymphocytes/immunology , Cross-Sectional Studies , Female , Humans , Immunoglobulin G/immunology , Immunologic Memory/immunology , Male , Middle Aged , Nucleocapsid Proteins/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes/immunologyABSTRACT
We quantified the serum levels of 34 cytokines/chemokines in 30 patients with SARS-CoV-2 infection. Elevated levels of IP-10 and IL-7 were detected in the acute and convalescent stages of the infection and were highly associated with disease severity.