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1.
Clin Lab Med ; 42(1): 97-109, 2022 03.
Article in English | MEDLINE | ID: covidwho-2130422

ABSTRACT

Humoral immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during acute infection and convalescence has been widely studied since March 2020. In this review, the authors summarize literature on humoral responses to SARS-CoV-2 antigens with a focus on spike, nucleocapsid, and the receptor-binding domain as targets of antibody responses. They highlight serologic studies during acute SARS-CoV-2 infection and discuss the clinical relevance of antibody levels in COVID-19 progression. Antibody responses in pediatric COVID-19 patients are also reviewed. Finally, the authors discuss antibody responses during convalescence and their role in protection from SARS-CoV-2 reinfection.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Antibody Formation , Child , Humans , Immunity, Humoral
2.
Clin Lab Med ; 42(1): 75-84, 2022 03.
Article in English | MEDLINE | ID: covidwho-2130421

ABSTRACT

This review describes the underlying basis for the sup-optimal humoral immune response in coronavirus disease (COVID)-19 including the absence of evidence for affinity maturation in the vast majority of patients and the absence of germinal centers even in severe disease. Suboptimal humoral and cellular immunity may provide the optimal conditions for the generation and selection of viral variants.


Subject(s)
COVID-19 , Immunity, Humoral , Antibodies, Viral , Humans , Immunity, Cellular , SARS-CoV-2
3.
Infection ; 50(6): 1475-1481, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2129444

ABSTRACT

BACKGROUND: The immune response to COVID-19-vaccination differs between naïve vaccinees and those who were previously infected with SARS-CoV-2. Longitudinal quantitative and qualitative serological differences in these two distinct immunological subgroups in response to vaccination are currently not well studied. METHODS: We investigate a cohort of SARS-CoV-2-naïve and COVID-19-convalescent individuals immediately after vaccination and 6 months later. We use different enzyme-linked immunosorbent assay (ELISA) variants and a surrogate virus neutralization test (sVNT) to measure IgG serum titers, IgA serum reactivity, IgG serum avidity and neutralization capacity by ACE2 receptor competition. RESULTS: Anti-receptor-binding domain (RBD) antibody titers decline over time in dually vaccinated COVID-19 naïves whereas titers in single dose vaccinated COVID-19 convalescents are higher and more durable. Similarly, antibody avidity is considerably higher among boosted COVID-19 convalescent subjects as compared to dually vaccinated COVID-19-naïve subjects. Furthermore, sera from boosted convalescents inhibited the binding of spike-protein to ACE2 more efficiently than sera from dually vaccinated COVID-19-naïve subjects. CONCLUSIONS: Long-term humoral immunity differs substantially between dually vaccinated SARS-CoV-2-naïve and COVID-19-convalescent individuals. Booster vaccination after COVID-19 induces a more durable humoral immune response in terms of magnitude and quality as compared to two-dose vaccination in a SARS-CoV-2-naïve background.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/prevention & control , Immunity, Humoral , Angiotensin-Converting Enzyme 2 , Immunoglobulin G , Antibodies, Viral , Antibodies, Neutralizing
4.
Int J Infect Dis ; 111: 68-75, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-2113638

ABSTRACT

BACKGROUND: The cross-reactive antibody response against seasonal human coronaviruses (HCoVs) was evaluated according to disease severity in patients with COVID-19 in Japan. METHODS: In total, 194 paired serum samples collected from 97 patients with COVID-19 (mild, 35; severe, 62) were analyzed on admission and during convalescence. IgG antibodies against the nucleocapsid (N) and spike (S) proteins of SARS-CoV-2 and four seasonal HCoVs (HCoV-NL63, -229E, -OC43, and -HKU1) were detected by enzyme-linked immunosorbent assays. RESULTS: There was no difference in optical density (OD) values for seasonal HCoVs on admission between the severe and mild cases. In addition, a specific pattern of disease severity-associated OD values for HCoVs was not identified. Significant increases in OD values from admission to convalescence for HCoV-HKU1and -OC43 IgG-S, and for HCoV-NL63 and -229E IgG-N were observed in the severe cases. Significant differences were observed between the mild and severe cases for HCoV-HKU1 and -OC43 IgG-S OD values during convalescence. Correlations were found between the fold changes for HCoV-OC43 IgG-S OD values, and for SARS-CoV-2 IgG-S OD values, and C-reactive protein, lactate dehydrogenase, and lymphocyte levels. CONCLUSION: There was no association between the antibody titer for seasonal HCoVs in the early phase of COVID-19 and disease severity.


Subject(s)
COVID-19 , Humans , Immunity, Humoral , SARS-CoV-2 , Seasons , Severity of Illness Index , Spike Glycoprotein, Coronavirus
5.
Immunol Cell Biol ; 100(10): 750-752, 2022 11.
Article in English | MEDLINE | ID: covidwho-2113212

ABSTRACT

A recently published article has confirmed that a novel immunization method of sustained and escalating antigen delivery augments the magnitude, quality and durability of humoral immune responses.


Subject(s)
HIV-1 , Immunity, Humoral , Germinal Center , Antigens , Immunization
6.
Front Immunol ; 13: 1031254, 2022.
Article in English | MEDLINE | ID: covidwho-2119769

ABSTRACT

Emerging variants of concern (VOC) raise obstacles in shaping vaccination strategies and ending the pandemic. Vaccinated SARS-CoV-2 convalescence shapes the current immune dynamics. We analyzed the SARS-CoV-2 VOC-specific cellular and humoral response of 57 adults: 42 convalescent mRNA vaccinated patients (C+V+), 8 uninfected mRNA vaccinated (C-V+) and 7 unvaccinated convalescent individuals (C+V-). While C+V+ demonstrated a superior humoral SARS-CoV-2 response against all analyzed VOC (alpha, delta, omicron) compared to C-V+ and C+V-, SARS-CoV-2 reactive CD4+ and CD8+ T cells, which can cross-recognize the alpha, delta and omicron VOC after infection and/or vaccination were observed in all there groups without significant differences between the groups. We observed a preserved cross-reactive C+V+ and C-V+ T cell memory. An inferior humoral response but preserved cross-reactive T cell memory in C+V- compared to C+V+ was observed, as well as an inferior humoral response but preserved cross-reactive T cell memory in C+V- compared to C-V+. Adaptive immunity generated after SARS-CoV-2 infection and vaccination leads to superior humoral immune response against VOC compared to isolated infection or vaccination. Despite the apparent loss of neutralization potential caused by viral evolution, a preserved SARS-CoV-2 reactive T cell response with a robust potential for cross-recognition of the alpha, delta and omicron VOC was detected in all studied cohorts. Our results may have implications on current vaccination strategies.


Subject(s)
COVID-19 , Immunity, Humoral , Adult , Humans , SARS-CoV-2 , Convalescence , COVID-19/prevention & control , Antibodies, Viral , Vaccination , RNA, Messenger
7.
Nat Commun ; 13(1): 6866, 2022 Nov 11.
Article in English | MEDLINE | ID: covidwho-2119060

ABSTRACT

The effectiveness of a 3rd dose of SARS-CoV-2 vaccines waned quickly in the Omicron-predominant period. In response to fast-waning immunity and the threat of Omicron variant of concern (VOC) to healthcare workers (HCWs), we conduct a non-randomized trial (ChiCTR2200055564) in which 38 HCWs volunteer to receive a homologous booster of inactivated vaccines (BBIBP-CorV) 6 months after the 3rd dose. The primary and secondary outcomes are neutralizing antibodies (NAbs) and the receptor-binding domain (RBD)-directed antibodies, respectively. The 4th dose recalls waned immunity while having distinct effects on humoral responses to different antigens. The peak antibody response to the RBD induced by the 4th dose is inferior to that after the 3rd dose, whereas responses to the N-terminal domain (NTD) of spike protein are further strengthened significantly. Accordingly, the 4th dose further elevates the peak level of NAbs against ancestral SARS-CoV-2 and Omicron BA.2, but not BA.1 which has more NTD mutations. No severe adverse events related to vaccination are recorded during the trial. Here, we show that redistribution of immune focus after repeated vaccinations may modulate cross-protective immune responses against different VOCs.


Subject(s)
COVID-19 , Viral Vaccines , Humans , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Immunity, Humoral , Membrane Glycoproteins/genetics , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccines, Inactivated , Viral Envelope Proteins
8.
BMC Immunol ; 23(1): 57, 2022 Nov 16.
Article in English | MEDLINE | ID: covidwho-2117893

ABSTRACT

BACKGROUND: To determine the dynamic SARS-CoV-2 specific antibody levels induced by 3 doses of an inactivated COVID-19 vaccine, CoronaVac. An observational, prospective cohort study was performed with 93 healthy healthcare workers from a tertiary hospital in Nanjing, China. Serum SARS-CoV-2 specific IgM, IgG, and neutralizing antibodies (NAb) were measured at different time points among participants who received 3 doses of inactivated COVID-19 vaccine. RESULTS: 91.3% (85/93) and 100% (72/72) participants showed positive both for SARS-CoV-2 specific IgG and NAb after 2-dose CoronaVac and after 3-dose CoronaVac, respectively. Anti-SARS-CoV-2 IgG responses reached 91.21 (55.66-152.06) AU/mL, and surrogate NAb was 47.60 (25.96-100.81) IU/mL on day 14 after the second dose. Anti-SARS-CoV-2 IgG responses reached 218.29 (167.53-292.16) AU/mL and surrogate NAb was 445.54 (171.54-810.90) IU/mL on day 14 after the third dose. Additionally, SARS-CoV-2 specific surrogate neutralizing antibody titers were highly correlated with serum neutralization activities against Ancestral, Omicron, and Delta strains. Moreover, significantly higher SARS-CoV-2 IgG responses, but not NAb responses, were found in individuals with breakthrough infection when compared to that of 3-dose CoronaVac recipients. CONCLUSIONS: CoronaVac elicited robust SARS-CoV-2 specific humoral responses. Surrogate NAb assay might substitute for pseudovirus neutralization assay. Monitoring SARS-CoV-2 antibody responses induced by vaccination would provide important guidance for the optimization of COVID-19 vaccines.


Subject(s)
COVID-19 , Viral Vaccines , Humans , COVID-19 Vaccines , Immunity, Humoral , Prospective Studies , Vaccines, Inactivated , Longitudinal Studies , SARS-CoV-2 , COVID-19/prevention & control , Antibodies, Viral , Immunoglobulin G , Cohort Studies
9.
Front Immunol ; 13: 1027180, 2022.
Article in English | MEDLINE | ID: covidwho-2109770

ABSTRACT

Under the background of the severe human health and world economic burden caused by COVID-19, the attenuation of vaccine protection efficacy, and the prevalence and immune escape of emerging variants of concern (VOCs), the third dose of booster immunization has been put on the agenda. Systems biology approaches can help us gain new perspectives on the characterization of immune responses and the identification of factors underlying vaccine-induced immune efficacy. We analyzed the antibody signature and transcriptional responses of participants vaccinated with COVID-19 inactivated vaccine and protein subunit vaccine as a third booster dose. The results from the antibody indicated that the third booster dose was effective, and that heterologous vaccination with the protein subunit vaccine as a booster dose induced stronger humoral immune responses than the homologous vaccination with inactivated vaccine, and might be more effective against VOCs. In transcriptomic analysis, protein subunit vaccine induced more differentially expressed genes that were significantly associated with many important innate immune pathways. Both the homologous and heterologous boosters could increase the effectiveness against COVID-19, and compared with the inactivated vaccine, the protein subunit vaccine, mediated a stronger humoral immune response and had a more significant correlation with the innate immune function module, which provided certain data support for the third booster immunization strategy.


Subject(s)
COVID-19 , Immunity, Humoral , Humans , Transcriptome , Protein Subunits , Immunization, Secondary , COVID-19/prevention & control , Vaccines, Inactivated , Vaccines, Subunit
10.
Front Immunol ; 13: 988304, 2022.
Article in English | MEDLINE | ID: covidwho-2109765

ABSTRACT

Longitudinal humoral immune response to inactivated COVID-19 vaccines among people living with HIV (PLWH) have not yet been systematically investigated. We conducted a 6-month longitudinal study among vaccinated PLWH and HIV-Negative Controls (HNC) to determine whether the humoral immune response effects of the inactivated COVID-19 vaccine are different between the two groups of people. Totally, 46 PLWH and 38 HNC who received the inactivated COVID-19 vaccine on days 0 and 28 were enrolled. The SARS-CoV-2 neutralizing antibodies (nAbs) and total specific IgM and IgG antibodies were examined on Day 0-Day190. The level and positive seroconversion rate of nAbs peaked on Day 42 in HNC while peaked on Day 70 in PLWH, then decreased gradually with the extension of the vaccination period after the peaks. The peak level of nAbs in PLWH on Day 70, (GMC 8.07 BAU/mL, 95% CI 5.67-11.48) was significantly lower than in HNC on Day 42 (GMC 18.28 BAU/mL, 95% CI 10.33-32.33, P =0.03). The decrease in the geometric mean concentrations (GMCs) of nAbs was observed as 42.9% in PLWH after peak level, which decreased from 8.07 BAU/mL [95% CI: 5.67-11.48] on Day 70 to 4.61 BAU/mL [95% CI: 3.35-6.34] on Day 190 (p = 0.02). On Day 190, only seven (18%, [95% CI: 6-40]) HNC and five (11%, [95% CI: 4-25]) PLWH maintained positive nAbs response respectively. The geometric mean ELISA units (GMEUs) and positive seroconversion rate of IgG in PLWH dropped significantly from Day 70 (GMEUs, 0.20 EU/mL, [95% CI: 0.13-0.34]; seroconversion, 52%, [95% CI: 34-69]) to Day 190 (GMEUs, 0.05 EU/mL, [95% CI: 0.03-0.08], P<0.001; seroconversion, 18%, [95% CI: 8-33], P<0.001). There was no significant difference in levels and seroconversion rates of nAbs and IgG between the two groups on Day 190. The peak immunogenicity of the inactivated COVID-19 vaccine was delayed and inferior in PLWH compared to HNC, while no significant difference was found in six-month immunogenicity between the two groups.


Subject(s)
COVID-19 , HIV Infections , Humans , COVID-19 Vaccines , Immunity, Humoral , Longitudinal Studies , Vaccines, Inactivated , SARS-CoV-2 , COVID-19/prevention & control , Antibodies, Neutralizing , Immunoglobulin G
11.
Front Immunol ; 13: 960709, 2022.
Article in English | MEDLINE | ID: covidwho-2109764

ABSTRACT

Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly contagious disease that affects the global pig industry. To understand mechanisms of susceptibility/resistance to PRRSV, this study profiled the time-serial white blood cells transcriptomic and serum metabolomic responses to PRRSV in piglets from a crossbred population of PRRSV-resistant Tongcheng pigs and PRRSV-susceptible Large White pigs. Gene set enrichment analysis (GSEA) illustrated that PRRSV infection up-regulated the expression levels of marker genes of dendritic cells, monocytes and neutrophils and inflammatory response, but down-regulated T cells, B cells and NK cells markers. CIBERSORT analysis confirmed the higher T cells proportion in resistant pigs during PRRSV infection. Resistant pigs showed a significantly higher level of T cell activation and lower expression levels of monocyte surface signatures post infection than susceptible pigs, corresponding to more severe suppression of T cell immunity and inflammatory response in susceptible pigs. Differentially expressed genes between resistant/susceptible pigs during the course of infection were significantly enriched in oxidative stress, innate immunity and humoral immunity, cell cycle, biotic stimulated cellular response, wounding response and behavior related pathways. Fourteen of these genes were distributed in 5 different QTL regions associated with PRRSV-related traits. Chemokine CXCL10 levels post PRRSV infection were differentially expressed between resistant pigs and susceptible pigs and can be a promising marker for susceptibility/resistance to PRRSV. Furthermore, the metabolomics dataset indicated differences in amino acid pathways and lipid metabolism between pre-infection/post-infection and resistant/susceptible pigs. The majority of metabolites levels were also down-regulated after PRRSV infection and were significantly positively correlated to the expression levels of marker genes in adaptive immune response. The integration of transcriptome and metabolome revealed concerted molecular events triggered by the infection, notably involving inflammatory response, adaptive immunity and G protein-coupled receptor downstream signaling. This study has increased our knowledge of the immune response differences induced by PRRSV infection and susceptibility differences at the transcriptomic and metabolomic levels, providing the basis for the PRRSV resistance mechanism and effective PRRS control.


Subject(s)
Porcine Reproductive and Respiratory Syndrome , Porcine respiratory and reproductive syndrome virus , Animals , Swine , Porcine respiratory and reproductive syndrome virus/genetics , Porcine Reproductive and Respiratory Syndrome/genetics , Transcriptome , Immunity, Humoral , Adaptive Immunity/genetics
12.
JCI Insight ; 7(21)2022 Nov 08.
Article in English | MEDLINE | ID: covidwho-2108450

ABSTRACT

People living with HIV-1 (PLWH) exhibit more rapid antibody decline following routine immunization and elevated baseline chronic inflammation than people without HIV-1 (PWOH), indicating potential for diminished humoral immunity during SARS-CoV-2 infection. Conflicting reports have emerged on the ability of PLWH to maintain humoral protection against SARS-CoV-2 coinfection during convalescence. It is unknown whether peak COVID-19 severity, along with HIV-1 infection status, associates with the quality and quantity of humoral immunity following recovery. Using a cross-sectional observational cohort from the United States and Peru, adults were enrolled 1-10 weeks after SARS-CoV-2 infection diagnosis or symptom resolution. Serum antibodies were analyzed for SARS-CoV-2-specific response rates, binding magnitudes, ACE2 receptor blocking, and antibody-dependent cellular phagocytosis. Overall, (a) PLWH exhibited a trend toward decreased magnitude of SARS-CoV-2-specific antibodies, despite modestly increased overall response rates when compared with PWOH; (b) PLWH recovered from symptomatic outpatient COVID-19 had comparatively diminished immune responses; and (c) PLWH lacked a corresponding increase in SARS-CoV-2 antibodies with increased COVID-19 severity when asymptomatic versus symptomatic outpatient disease was compared.


Subject(s)
COVID-19 , HIV-1 , Humans , Antibodies, Viral , Cross-Sectional Studies , Immunity, Humoral , SARS-CoV-2 , Adult
13.
Sci Rep ; 12(1): 18929, 2022 Nov 07.
Article in English | MEDLINE | ID: covidwho-2106455

ABSTRACT

To reveal waning humoral immunity after second dose BNT162b2 vaccinations in a rural Japanese community and determine factors affecting antibody titers. We aimed to report Immunoglobulin G (IgG) antibody against the SARS-CoV-2 spike (S1) protein levels and neutralizing activity in a large scale community based cohort. METHODS: Participants in the observational cross-sectional study received a second dose of vaccination with BNT162b2 (Pfizer/BioNTech) and were not previously infected with COVID-19. Questionnaire-collected data on sex, age, adverse vaccine reactions, and medical history was obtained. RESULTS: Data from 2496 participants revealed that older age groups reached a low antibody titer 90-120 days after the second vaccination. Neutralizing activity decreased with age; 35 (13.3%) of those aged ≥ 80 years had neutralizing activity under the cut-off value. Neutralizing activity > 179 days from the second vaccination was 11.6% compared to that at < 60 days from the second vaccination. Significantly lower IgG antibody titers and neutralizing activity were associated with age, male sex, increased time from second vaccination, smoking, steroids, immunosuppression, and comorbidities. CONCLUSIONS: Antibody titer decreased substantially over time. Susceptible populations, older people, men, smokers, steroid users, immunosuppression users, and people with three or more comorbidities may require a special protection strategy.


Subject(s)
COVID-19 , Vaccines , Male , Humans , Aged , Immunity, Humoral , Cross-Sectional Studies , BNT162 Vaccine , Antibodies, Viral , Japan , SARS-CoV-2 , COVID-19/prevention & control , Vaccination , Surveys and Questionnaires , Antibodies, Neutralizing
15.
Mol Immunol ; 152: 153-161, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2105609

ABSTRACT

Antibodies represent key effectors of the adaptive immune system. The specificity of antibodies is an established hallmark of the immune response. However, a certain proportion of antibodies exhibit limited promiscuity or multireactivity. Germline antibodies display plasticity which imparts multispecificity to enhance the antibody repertoire. Surprisingly, even affinity matured antibodies display such plasticity and multireactivity enabling their binding to more than one antigen. We propose that antibody multispecificity is a physiological requirement to expand the antibody repertoire at the germline level and to tolerate plasticity in antigens at the mature level. This property of the humoral immune response may attenuate the ability of infectious RNA viruses such as influenza, HIV and SARS-CoV-2 to acquire mutations that render resistance to neutralizing antibodies.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Antibodies, Neutralizing , Antigens , Immunity, Humoral
16.
Immunobiology ; 227(6): 152287, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2105123

ABSTRACT

BACKGROUND: Epitope selection is the key to peptide vaccines development. Bioinformatics tools can efficiently improve the screening of antigenic epitopes and help to choose the right ones. OBJECTIVE: To predict, synthesize and testify peptide epitopes at spike protein, assess the effect of mutations on epitope humoral immunity, thus provide clues for the design and development of epitope peptide vaccines against SARS-CoV-2. METHODS: Bioinformatics servers and immunological tools were used to identify the helper T lymphocyte, cytotoxic T lymphocyte, and linear B lymphocyte epitopes on the S protein of SARS-CoV-2. Physicochemical properties of candidate epitopes were analyzed using IEDB, VaxiJen, and AllerTOP online software. Three candidate epitopes were synthesized and their antigenic responses were evaluated by binding antibody detection. RESULTS: A total of 20 antigenic, non-toxic and non-allergenic candidate epitopes were identified from 1502 epitopes, including 6 helper T-cell epitopes, 13 cytotoxic T-cell epitopes, and 1 linear B cell epitope. After immunization with antigen containing candidate epitopes S206-221, S403-425, and S1157-1170 in rabbits, the binding titers of serum antibody to the corresponding peptide, S protein, receptor-binding domain protein were (415044, 2582, 209.3), (852819, 45238, 457767) and (357897, 10528, 13.79), respectively. The binding titers to Omicron S protein were 642, 12,878 and 7750, respectively, showing that N211L, DEL212 and K417N mutations cause the reduction of the antibody binding activity. CONCLUSIONS: Bioinformatic methods are effective in peptide epitopes design. Certain mutations of the Omicron would lead to the loss of antibody affinity to Omicron S protein.


Subject(s)
COVID-19 , Viral Vaccines , Animals , Humans , Rabbits , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/chemistry , Computational Biology/methods , Epitopes, T-Lymphocyte/genetics , COVID-19 Vaccines/genetics , Immunity, Humoral , Epitopes, B-Lymphocyte/genetics , Vaccines, Subunit , Peptides
17.
Viruses ; 14(11)2022 Nov 06.
Article in English | MEDLINE | ID: covidwho-2099865

ABSTRACT

In this study, we aimed to determine the effect of COVID-19 vaccination on 3-month immune response and durability after natural infection by the Omicron variant and to assess the immune response to a fourth dose of COVID-19 vaccination in patients with prior natural infection with the Omicron variant. Overall, 86 patients aged ≥60 years with different vaccination histories and 39 health care workers (HCWs) vaccinated thrice before Omicron infection were enrolled. The sVNT50 titer was significantly lower in patients with incomplete vaccination before SARS-CoV-2 infection with the S clade (p < 0.001), Delta variant (p < 0.001), or Omicron variant (p = 0.003) than in those vaccinated thrice. The sVNT results against the Omicron variant did not differ significantly in patients aged ≥60 years (p = 0.49) and HCWs (p = 0.17), regardless of the recipient receiving the fourth dose 2 months after COVID-19. Incomplete COVID-19 vaccination before Omicron infection for individuals aged ≥60 years conferred limited protection against homologous and heterologous virus strains, whereas two or three doses of the vaccine provided cross-variant humoral immunity against Omicron infection for at least 3 months. However, a fourth dose 2 months after Omicron infection did not enhance immunity against the homologous strain. A future strategy using the bivalent Omicron-containing booster vaccine with appropriate timing will be crucial.


Subject(s)
COVID-19 , Viral Vaccines , Humans , Immunity, Humoral , COVID-19/prevention & control , COVID-19 Vaccines , SARS-CoV-2 , Vaccination , Antibodies, Viral
18.
Front Immunol ; 13: 1042406, 2022.
Article in English | MEDLINE | ID: covidwho-2099154

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes asymptomatic or mild symptoms, even rare hospitalization in children. A major concern is whether the pre-existing antibodies induced by low pathogenic human coronaviruses (LPH-CoVs) in children can cross-react with SARS-CoV-2. To address this unresolved question, we analyzed the pre-existing spike (S)-specific immunoglobin (Ig) G antibodies against LPH-CoVs and the cross-reactive antibodies against SARS-CoV-2 in 658 serum samples collected from children prior to SARS-CoV-2 outbreak. We found that the seroprevalence of these four LPH-CoVs reached 75.84%, and about 24.64% of the seropositive samples had cross-reactive IgG antibodies against the nucleocapsid, S, and receptor binding domain antigens of SARS-CoV-2. Additionally, the re-infections with different LPH-CoVs occurred frequently in children and tended to increase the cross-reactive antibodies against SARS-CoV-2. From the forty-nine serum samples with cross-reactive anti-S IgG antibodies against SARS-CoV-2, we found that seven samples with a median age of 1.4 years old had detected neutralizing activity for the wild-type or mutant SARS-CoV-2 S pseudotypes. Interestingly, all of the seven samples contained anti-S IgG antibodies against HCoV-OC43. Together, these data suggest that children's pre-existing antibodies to LPH-CoVs have limited cross-reactive neutralizing antibodies against SRAS-CoV-2.


Subject(s)
COVID-19 , Coronaviridae , Child , Humans , Infant , SARS-CoV-2 , Immunity, Humoral , Seroepidemiologic Studies , Antibodies, Viral , Immunoglobulin G
19.
PLoS One ; 17(11): e0276929, 2022.
Article in English | MEDLINE | ID: covidwho-2098767

ABSTRACT

Mortality due to COVID-19 is not increased in immunosuppressed individuals after liver transplantation (OLT) compared to individuals without immunosuppression. Data on long-term protective immunity against SARS-CoV-2 in immunosuppressed convalescents, is limited. We prospectively measured immune responses against SARS-CoV-2 by quantifying antibodies against 4 different antigens (spike protein 1 and 2, receptor binding domain, nucleocapsid) and T cell responses by IFN-γ ELISPOT against 4 antigens (membrane, nucleocapsid, spike protein 1 and 2) in 24 OLT convalescents with immunosuppressive therapy longitudinally in the first year after COVID-19 including a booster vaccination in comparison to a matched cohort of non-immunosuppressed convalescents (non-IS-Con). Pre-pandemic OLT samples were retrieved from our prospective OLT biorepository (n = 16). No relevant T cell reactivity or immunoglobulin G (IgG) against SARS-CoV-2 were detectable in pre-pandemic samples of OLT recipients despite reactivity against endemic corona-viruses. OLT convalescents had a lower prevalence of IgG against nucleocapsid (54% vs. 90%) but not against spike protein domains (98-100% vs. 100%) after vaccination in the second half-year after COVID-19 compared to non-IS-Con. Also, concentrations of anti-nucleocapsid IgG were lower in OLT convalescents than in non-IS-Con. Concentration of IgG against spike protein domains was significantly increased by a booster vaccination in OLT convalescents. But concentration of IgG against two of three spike protein domains remains slightly lower compared to non-IS-Con finally. However, none of these differences was mirrored by the cellular immunity against SARS-CoV-2 that remained stable during the first year after COVID-19 and was not further stimulated by a corona vaccination in OLT convalescents. In conclusion, despite lower concentrations of anti-SARS-CoV-2 IgG in OLT convalescents anti-SARS-CoV-2 cellular immunity was as robust as in non-IS-Con.


Subject(s)
COVID-19 , Liver Transplantation , Humans , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Prospective Studies , Antibodies, Viral , Immunoglobulin G , Immunity, Cellular , Immunity, Humoral , Vaccination , Transplant Recipients
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