Two‐Year Prospective Study of the Humoral Immune Response of Patients with Severe Acute Respiratory Syndrome

Liu, Wei; Fontanet, Arnaud; Zhang, Pan-He; Li, Zhan; Xin, Zhong-Tao; Baril, Laurence; Tang, Fang; Lv, Hui; Cao, Wu‐Chun

doi:10.1086/500469

Cited by 293 publications

(291 citation statements)

References 13 publications

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“…As seen in our previous studies (4,6), the humoral immunity continuously declined over time and eventually vanished in most patients. Only 2 of 23 patients maintained a low level of IgG Ab 6 y after disease onset.…”

Section: Discussionsupporting

confidence: 79%

“…Previous studies indicated that specific Abs to SARS-related coronavirus (SARS-CoV) waned over time. (4)(5)(6)(7)(8)(9) However, disappearance of anti-SARS-CoV Abs does not necessarily indicate loss of protection. As is well known, an efficient line of defense against viral reinfection consists of three key components: preexisting Abs, memory B cells, and memory T cells.…”

Section: S Evere Acute Respiratory Syndrome (Sars) Is An Emerging Infmentioning

confidence: 99%

“…The SARS patients were originally seen at one hospital in Beijing, which had been described in our previous studies (4,6). All the patients were clinically diagnosed according to the World Health Organization criteria (20) and then confirmed by serological tests.…”

Section: Subjectsmentioning

confidence: 99%

See 2 more Smart Citations

Lack of Peripheral Memory B Cell Responses in Recovered Patients with Severe Acute Respiratory Syndrome: A Six-Year Follow-Up Study

Tang

Yan

Xin

et al. 2011

The Journal of Immunology

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508

468

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Six years have passed since the outbreak of severe acute respiratory syndrome (SARS). Previous studies indicated that specific Abs to SARS-related coronavirus (SARS-CoV) waned over time in recovered SARS patients. It is critical to find out whether a potential anamnestic response, as seen with other viral infections, exists to protect a person from reinfection in case of another SARS outbreak. Recovered SARS patients were followed up to 6 y to estimate the longevity of specific Ab. The specific memory B cell and T cell responses to SARS-CoV Ags were measured by means of ELISPOT assay. Factors in relation to humoral and cellular immunity were investigated. Six years postinfection, specific IgG Ab to SARS-CoV became undetectable in 21 of the 23 former patients. No SARS-CoV Ag-specific memory B cell response was detected in either 23 former SARS patients or 22 close contacts of SARS patients. Memory T cell responses to a pool of SARS-CoV S peptides were identified in 14 of 23 (60.9%) recovered SARS patients, whereas there was no such specific response in either close contacts or healthy controls. Patients with more severe clinical manifestations seemed to present a higher level of Ag-specific memory T cell response. SARS-specific IgG Ab may eventually vanish and peripheral memory B cell responses are undetectable in recovered SARS patients. In contrast, specific T cell anamnestic responses can be maintained for at least 6 y. These findings have applications in preparation for the possible reemergence of SARS.

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Section: Discussionsupporting

confidence: 79%

Section: S Evere Acute Respiratory Syndrome (Sars) Is An Emerging Infmentioning

confidence: 99%

See 1 more Smart Citation

Lack of Peripheral Memory B Cell Responses in Recovered Patients with Severe Acute Respiratory Syndrome: A Six-Year Follow-Up Study

Tang

Yan

Xin

et al. 2011

The Journal of Immunology

Self Cite

508

468

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“…Serum IgG, IgM, and IgA responses to SARS-CoV occurred around the same time, with most patients seroconverting by day 14 after onset of illness (135). In a follow-up study of 56 subjects, ELISA IgG and neutralizing antibodies peaked at 4 months and dropped progressively over time; 11% of the subjects did not have detectable ELISA IgG antibodies to SARS 24 months postinfection, but neutralizing antibodies were still detectable (136). In a large study of 623 SARS patients, antibodies were able to neutralize pseudotyped viruses bearing S proteins from four different SARSCoV strains, suggesting that these antibodies were cross-reactive (137).…”

Section: Humoral Immune Response To Sars-cov Infectionmentioning

confidence: 97%

The Immunobiology of SARS

Chen

Subbarao

2007

Annu. Rev. Immunol.

262

277

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Severe acute respiratory syndrome (SARS) presented as an atypical pneumonia that progressed to acute respiratory distress syndrome in approximately 20% of cases and was associated with a mortality of about 10%. The etiological agent was a novel coronavirus (CoV). Angiotensin-converting enzyme 2 is the functional receptor for SARS-CoV; DC-SIGN and CD209L (L-SIGN) can enhance viral entry. Although the virus infects the lungs, gastrointestinal tract, liver, and kidneys, the disease is limited to the lungs, where diffuse alveolar damage is accompanied by a disproportionately sparse inflammatory infiltrate. Pro-inflammatory cytokines and chemokines, particularly IP-10, IL-8, and MCP-1, are elevated in the lungs and peripheral blood, but there is an unusual lack of an antiviral interferon (IFN) response. The virus is susceptible to exogenous type I IFN but suppresses the induction of IFN. Innate immunity is important for viral clearance in the mouse model. Virus-specific neutralizing antibodies that develop during convalescence prevent reinfection in animal models.

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“…Persistent levels of SARS-CoV IgG have been detected in SARS cases for several months and up to 2 years after disease onset (4,11,12,19,21). In this study, serum samples from 48 SARS patients from Vietnam and the United States were collected 221 to 735 days (44 from days 221 to 250; 4 from days 633 to 735) after the onset of illness and tested for the presence of SARS-CoV-and N-and S-protein-specific IgG by ELISA.…”

mentioning

confidence: 99%

Recombinant Protein-Based Assays for Detection of Antibodies to Severe Acute Respiratory Syndrome Coronavirus Spike and Nucleocapsid Proteins

Haynes

Miao

Harcourt

et al. 2007

Clin Vaccine Immunol

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Recombinant severe acute respiratory syndrome (SARS) nucleocapsid and spike protein-based immunoglobulin G immunoassays were developed and evaluated. Our assays demonstrated high sensitivity and specificity to the SARS coronavirus in sera collected from patients as late as 2 years postonset of symptoms. These assays will be useful not only for routine SARS coronavirus diagnostics but also for epidemiological and antibody kinetic studies.The 2003 outbreak of severe acute respiratory syndrome (SARS) lasted fewer than 9 months, yet it had a major impact on public health and socioeconomics. Since the end of the SARS outbreak, there have been 17 identified SARS-associated coronavirus (SARS-CoV) infections, 6 from direct laboratory exposure, 1 of which resulted in community transmission to seven individuals, and 4 sporadic, community-acquired infections (9). Since additional cases may occur and could, if undetected, quickly lead to another global outbreak, it is important to continue to improve our ability to reliably monitor SARS-CoV infections (3,16,18).As with other coronaviruses, the spike (S) and nucleocapsid (N) proteins are abundantly expressed during virus infection and are most effective among the coronavirus structural proteins at inducing antibody responses (10,14,15,23). Previous studies have demonstrated the utility of anti-N and anti-S proteins in the diagnosis of SARS-CoV infections (2,5,12,21). In this study, we describe the evaluation and comparison of recombinant spike and nucleocapsid enzyme-linked immunosorbent assays (ELISAs) for specifically detecting SARS-CoV infection.The recombinant full-length SARS N gene was amplified from SARS-CoV RNA (Urbani strain), modified to contain a C-terminal His 6 tag, and cloned into the Venezuelan equine encephalitis virus replicon vector (17). Baby hamster kidney (BHK) cells were transfected with SARS N replicon RNA by electroporation. Cells were harvested, and expressed protein was purified by metal affinity chromatography and analyzed by silver staining and Western blot analysis for the appropriately sized (50-kDa) immunoreactive protein (8). The control antigen, the nontoxic 50-kDa C-terminal fragment of the botulinum neurotoxin serotype A (BoNt/HcA), was expressed as described above (7).The soluble codon-optimized SARS-CoV S glycoprotein (170 kDa; amino acids 1 to 1190; S1190) and the control antigen, truncated angiotensin-converting enzyme 2 (120 kDa; glycosylated; tACE-2), were cloned into pcDNA3.1 Myc/His and expressed in HEK-293T/17 cells. The proteins were purified using metal-affinity chromatography and analyzed as described by Babcock et al. (1).Recombinant SARS N and S protein indirect ELISAs were developed using a modified version of the inactivated wholevirus ELISA described by Ksiazek et al. (6). Briefly, ELISA plates (Immulon) were coated with either purified recombinant N protein (12.5 ng/well) and the control antigen BoNT/ HcA or purified His 6 /c-myc-tagged recombinant S1190 protein (12.5 ng/well) and the control antigen tACE-2. The plates wer...

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Two‐Year Prospective Study of the Humoral Immune Response of Patients with Severe Acute Respiratory Syndrome

Cited by 293 publications

References 13 publications

Lack of Peripheral Memory B Cell Responses in Recovered Patients with Severe Acute Respiratory Syndrome: A Six-Year Follow-Up Study

Lack of Peripheral Memory B Cell Responses in Recovered Patients with Severe Acute Respiratory Syndrome: A Six-Year Follow-Up Study

The Immunobiology of SARS

Recombinant Protein-Based Assays for Detection of Antibodies to Severe Acute Respiratory Syndrome Coronavirus Spike and Nucleocapsid Proteins

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