Cross-Sectional Evaluation of Humoral Responses against SARS-CoV-2 Spike.
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ABSTRACT:
SUBMITTER: Prevost J
PROVIDER: S-EPMC7524645 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The causative agent of severe acute respiratory syndrome (SARS) has been identified as SARS-associated coronavirus (SARS-CoV), but the prophylactic treatment of SARS-CoV is still under investigation. We constructed a recombinant adenovirus containing a truncated N-terminal fragment of the SARS-CoV Spike (S) gene (from--45 to 1469, designated Ad-S(N)), which encoded a truncated S protein (490 amino-acid residues, a part of 672 amino-acid S1 subunit), and investigated whether this construct could induce effective immunity against SARS-CoV in Wistar rats. Rats were immunized either subcutaneously or intranasally with Ad-S(N) once a week for three consecutive weeks. Our results showed that all of the immunized animals generated humoral immunity against the SARS-CoV spike protein, and the sera of immunized rats showed strong capable of protecting from SARS-CoV infection in vitro. Histopathological examination did not find evident side effects in the immunized animals. These results indicate that an adenoviral-based vaccine carrying an N-terminal fragment of the Spike gene is able to elicit strong SARS-CoV-specific humoral immune responses in rats, and may be useful for the development of a protective vaccine against SARS-CoV infection.
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Project description:The standard regimen of the BNT162b2 mRNA vaccine for SARS-CoV-2 includes two doses administered three weeks apart. However, some public health authorities spaced these doses, raising questions about efficacy. We analyzed longitudinal humoral responses against the D614G strain and variants of concern for SARS-CoV-2 in a cohort of SARS-CoV-2-naive and previously infected individuals who received the BNT162b2 mRNA vaccine with sixteen weeks between doses. While administering a second dose to previously infected individuals did not significantly improve humoral responses, these responses significantly increased in naive individuals after a 16-week spaced second dose, achieving similar levels as in previously infected individuals. Comparing these responses to those elicited in individuals receiving a short (4-week) dose interval showed that a 16-week interval induced more robust responses among naive vaccinees. These findings suggest that a longer interval between vaccine doses does not compromise efficacy and may allow greater flexibility in vaccine administration.
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Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently causing a global pandemic. The antigen specificity of the antibody response mounted against this novel virus is not understood in detail. Here, we report that subjects with a more severe SARS-CoV-2 infection exhibit a larger antibody response against the spike and nucleocapsid protein and epitope spreading to subdominant viral antigens, such as open reading frame 8 and nonstructural proteins. Subjects with a greater antibody response mounted a larger memory B cell response against the spike, but not the nucleocapsid protein. Additionally, we revealed that antibodies against the spike are still capable of binding the D614G spike mutant and cross-react with the SARS-CoV-1 receptor binding domain. Together, this study reveals that subjects with a more severe SARS-CoV-2 infection exhibit a greater overall antibody response to the spike and nucleocapsid protein and a larger memory B cell response against the spike.IMPORTANCE With the ongoing pandemic, it is critical to understand how natural immunity against SARS-CoV-2 and COVID-19 develops. We have identified that subjects with more severe COVID-19 disease mount a more robust and neutralizing antibody response against SARS-CoV-2 spike protein. Subjects who mounted a larger response against the spike also mounted antibody responses against other viral antigens, including the nucleocapsid protein and ORF8. Additionally, this study reveals that subjects with more severe disease mount a larger memory B cell response against the spike. These data suggest that subjects with more severe COVID-19 disease are likely better protected from reinfection with SARS-CoV-2.
| S-EPMC7845638 | biostudies-literature
Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently causing a global pandemic. The antigen specificity and kinetics of the antibody response mounted against this novel virus are not understood in detail. Here, we report that subjects with a more severe SARS-CoV-2 infection exhibit a larger antibody response against the spike and nucleocapsid protein and epitope spreading to subdominant viral antigens, such as open reading frame 8 and non-structural proteins. Subjects with a greater antibody response mounted a larger memory B cell response against the spike, but not the nucleocapsid protein. Additionally, we revealed that antibodies against the spike are still capable of binding the D614G spike mutant and cross-react with the SARS-CoV-1 receptor binding domain. Together, this study reveals that subjects with a more severe SARS-CoV-2 infection exhibit a greater overall antibody response to the spike and nucleocapsid protein and a larger memory B cell response against the spike.
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Project description:The SARS-CoV-2 Omicron variant (B.1.1.529) has multiple spike protein mutations1,2 that contribute to viral escape from antibody neutralization3-6 and reduce vaccine protection from infection7,8. The extent to which other components of the adaptive response such as T cells may still target Omicron and contribute to protection from severe outcomes is unknown. Here we assessed the ability of T cells to react to Omicron spike protein in participants who were vaccinated with Ad26.CoV2.S or BNT162b2, or unvaccinated convalescent COVID-19 patients (n = 70). Between 70% and 80% of the CD4+ and CD8+ T cell response to spike was maintained across study groups. Moreover, the magnitude of Omicron cross-reactive T cells was similar for Beta (B.1.351) and Delta (B.1.617.2) variants, despite Omicron harbouring considerably more mutations. In patients who were hospitalized with Omicron infections (n = 19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those in patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n = 49). Thus, despite extensive mutations and reduced susceptibility to neutralizing antibodies of Omicron, the majority of T cell responses induced by vaccination or infection cross-recognize the variant. It remains to be determined whether well-preserved T cell immunity to Omicron contributes to protection from severe COVID-19 and is linked to early clinical observations from South Africa and elsewhere9-12.
| S-EPMC8930768 | biostudies-literature
Project description:Identification of relevant epitopes is crucial for the development of subunit peptide vaccines inducing neutralizing and cellular immunity against SARS-CoV-2. Our aim was the characterization of epitopes in the receptor-binding domain (RBD) of SARS-CoV-2 spike (S) protein to generate a peptide vaccine. Epitope mapping using a panel of 10 amino acid overlapped 15-mer peptides covering region 401-515 from RBD did not identify linear epitopes when tested with sera from infected individuals or from RBD-immunized mice. However, immunization of mice with these 15-mer peptides identified four peptides located at region 446-480 that induced antibodies recognizing the peptides and RBD/S1 proteins. Immunization with peptide 446-480 from S protein formulated with Freund's adjuvant or with CpG oligodeoxinucleotide/Alum induced polyepitopic antibody responses in BALB/c and C56BL/6J mice, recognizing RBD (titres of 3 × 104-3 × 105, depending on the adjuvant) and displaying neutralizing capacity (80-95% inhibition capacity; p < 0.05) against SARS-CoV-2. Murine CD4 and CD8T-cell epitopes were identified in region 446-480 and vaccination experiments using HLA transgenic mice suggested the presence of multiple human T-cell epitopes. Antibodies induced by peptide 446-480 showed broad recognition of S proteins and S-derived peptides belonging to SARS-CoV-2 variants of concern. Importantly, vaccination with peptide 446-480 or with a cyclic version of peptide 446-488 containing a disulphide bridge between cysteines 480 and 488, protected humanized K18-hACE2 mice from a lethal dose of SARS-CoV-2 (62.5 and 75% of protection; p < 0.01 and p < 0.001, respectively). This region could be the basis for a peptide vaccine or other vaccine platforms against Covid-19.
| S-EPMC8480813 | biostudies-literature
Project description: Not available
| EMPIAR-10947 | biostudies-other
Project description:BackgroundFew studies have compared SARS-CoV-2 vaccine immunogenicity by ethnic group. We sought to establish whether cellular and humoral immune responses to SARS-CoV-2 vaccination differ according to ethnicity in UK Healthcare workers (HCWs).MethodsIn this cross-sectional analysis, we used baseline data from two immunological cohort studies conducted in HCWs in Leicester, UK. Blood samples were collected between March 3, and September 16, 2021. We excluded HCW who had not received two doses of SARS-CoV-2 vaccine at the time of sampling and those who had serological evidence of previous SARS-CoV-2 infection. Outcome measures were SARS-CoV-2 spike-specific total antibody titre, neutralising antibody titre and ELISpot count. We compared our outcome measures by ethnic group using univariable (t tests and rank-sum tests depending on distribution) and multivariable (linear regression for antibody titres and negative binomial regression for ELISpot counts) tests. Multivariable analyses were adjusted for age, sex, vaccine type, length of interval between vaccine doses and time between vaccine administration and sample collection and expressed as adjusted geometric mean ratios (aGMRs) or adjusted incidence rate ratios (aIRRs). To assess differences in the early immune response to vaccination we also conducted analyses in a subcohort who provided samples between 14 and 50 days after their second dose of vaccine.FindingsThe total number of HCWs in each analysis were 401 for anti-spike antibody titres, 345 for neutralising antibody titres and 191 for ELISpot. Overall, 25.4% (19.7% South Asian and 5.7% Black/Mixed/Other) were from ethnic minority groups. In analyses including the whole cohort, neutralising antibody titres were higher in South Asian HCWs than White HCWs (aGMR 1.47, 95% CI [1.06-2.06], P = 0.02) as were T cell responses to SARS-CoV-2 S1 peptides (aIRR 1.75, 95% CI [1.05-2.89], P = 0.03). In a subcohort sampled between 14 and 50 days after second vaccine dose, SARS-CoV-2 spike-specific antibody and neutralising antibody geometric mean titre (GMT) was higher in South Asian HCWs compared to White HCWs (9616 binding antibody units (BAU)/ml, 95% CI [7178-12,852] vs 5888 BAU/ml [5023-6902], P = 0.008 and 2851 95% CI [1811-4487] vs 1199 [984-1462], P < 0.001 respectively), increments which persisted after adjustment (aGMR 1.26, 95% CI [1.01-1.58], P = 0.04 and aGMR 2.01, 95% CI [1.34-3.01], P = 0.001). SARS-CoV-2 ELISpot responses to S1 and whole spike peptides (S1 + S2 response) were higher in HCWs from South Asian ethnic groups than those from White groups (S1: aIRR 2.33, 95% CI [1.09-4.94], P = 0.03; spike: aIRR, 2.04, 95% CI [1.02-4.08]).InterpretationThis study provides evidence that, in an infection naïve cohort, humoral and cellular immune responses to SARS-CoV-2 vaccination are stronger in South Asian HCWs than White HCWs. These differences are most clearly seen in the early period following vaccination. Further research is required to understand the underlying mechanisms, whether differences persist with further exposure to vaccine or virus, and the potential impact on vaccine effectiveness.FundingDIRECT and BELIEVE have received funding from UK Research and Innovation (UKRI) through the COVID-19 National Core Studies Immunity (NCSi) programme (MC_PC_20060).
| S-EPMC10071048 | biostudies-literature
Project description:BackgroundImmunocompromised patients are at increased risk of severe COVID-19 and impaired vaccine response. In this observational prospective study, we evaluated immunogenicity of the BNT162b2 mRNA vaccine in cohorts of primary or secondary immunocompromised patients.MethodsFive clinical groups of immunocompromised patients [primary immunodeficiency (PID) (n=57), people living with HIV (PLWH) (n=27), secondary immunocompromised patients with a broad variety of underlying rheumatologic (n=23) and homogeneous (multiple sclerosis) neurologic (n=53) conditions and chronic kidney disease (CKD) (n=39)] as well as a healthy control group (n=54) were included. Systemic humoral and cellular immune responses were evaluated by determination of anti-SARS-CoV-2 Spike antibodies using a TrimericS IgG assay (Diasorin) and through quantification of interferon gamma release in response to SARS-CoV-2 antigen with QuantiFERON SARS-CoV-2 assay (Qiagen), respectively. Responses were measured at pre-defined time-points after complete vaccination.ResultsAll healthy controls, PLWH and CKD-patients had detectable antibodies 10 to 14 days (T2) and 3 months (T3) after administration of the second vaccination. In contrast, only 94.5% of the PID, 50.0% of the rheumatologic and 48.0% of neurologic patients developed antibodies at T2 and only 89.1% of the PID, 52.4% of the rheumatologic and 50.0% of neurologic patients developed antibodies at T3. At T3 no significant differences in cellular response between the healthy control group and the PLWH and CKD groups were found, while proportions of reactive subjects were lower in PID and rheumatologic patients and higher in neurologic patients. Humoral and cellular immune responses significantly correlated in the healthy control, PID, PLWH groups for all 3 antigens.ConclusionPatients with acquired or inherited immune disorders may show variable immune responses to vaccination with the BNT162b2 mRNA vaccine against SARS-CoV-2. Whether humoral, cellular or both immune responses are delayed depends on the patient group, therapy and individual risk factors. These data may guide the counselling of patients with immune disorders regarding vaccination of SARS-CoV-2.
| S-EPMC8988283 | biostudies-literature