Seropositivity to Nucleoprotein to detect mild and asymptomatic SARS-CoV-2 infections: A complementary tool to detect breakthrough infections after COVID-19 vaccination?

Hoogen, Lotus L. van den; Smits, Gaby; Hagen, Cheyenne C. E. van; Wong, Denise; Vos, Eric R. A.; Boven, Michiel van; Melker, Hester E. de; Vliet, Jeffrey van; Kuijer, Marjan; Woudstra, Linde; Wijmenga-Monsuur, Alienke J.; GeurtsvanKessel, Corine H.; Stoof, Susanne P.; Reukers, Daphne F M; Wijsman, Lisa; Meijer, Adam; Reusken, Chantal; Rots, Nynke Y.; Klis, Fiona R.M. van der; Binnendijk, Robert S. van; Hartog, Gerco den

doi:10.1016/j.vaccine.2022.03.009

Cited by 40 publications

(55 citation statements)

References 29 publications

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“…Participants received two doses of the mRNA-based BNT162b2 vaccine, with a median interval of 35 days (range 35–37 days). According to a questionnaire, these vaccinated subjects had not been previously infected with SARS-CoV-2 and also tested negative for the presence of antibodies against SARS-CoV-2 nucleocapsid protein [ 31 ], and negative for presence of anti-S1 antibodies at pre-vaccination. Blood samples were taken 28 days (range 26–42 days) after their second vaccine dose.…”

Section: Methodsmentioning

confidence: 99%

Omicron BA.1 Mutations in SARS-CoV-2 Spike Lead to Reduced T-Cell Response in Vaccinated and Convalescent Individuals

Emmelot

Vos

Boer

et al. 2022

Viruses

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Omicron BA.1 variant can readily infect people with vaccine-induced or naturally acquired SARS-CoV-2 immunity facilitated by escape from neutralizing antibodies. In contrast, T-cell reactivity against the Omicron BA.1 variant seems relatively well preserved. Here, we studied the preexisting T cells elicited by either vaccination with the mRNA-based BNT162b2 vaccine or by natural infection with ancestral SARS-CoV-2 for their cross-reactive potential to 20 selected CD4+ T-cell epitopes of spike-protein-harboring Omicron BA.1 mutations. Although the overall memory CD4+ T-cell responses primed by the ancestral spike protein was still preserved generally, we show here that there is also a clear loss of memory CD4+ T-cell cross-reactivity to immunodominant epitopes across the spike protein due to Omicron BA.1 mutations. Complete or partial loss of preexisting T-cell responsiveness was observed against 60% of 20 nonconserved CD4+ T-cell epitopes predicted to be presented by a broad set of common HLA class II alleles. Monitoring such mutations in circulating strains helps predict which virus variants may escape previously induced cellular immunity and could be of concern.

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Section: Methodsmentioning

confidence: 99%

Omicron BA.1 Mutations in SARS-CoV-2 Spike Lead to Reduced T-Cell Response in Vaccinated and Convalescent Individuals

Emmelot

Vos

Boer

et al. 2022

Viruses

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“…Our work, along with others [36][37][38], describes the use of nucleoprotein antibody detection as a tool to identify natural infection using serum collected post-vaccination. This assay could be used to further define and refine correlates of protection, or generate a better predictor of breakthrough risk, by stratifying post-vaccination serum into those that had and had not been previously infected.…”

Section: Discussionmentioning

confidence: 99%

Impact of prior infection on SARS-CoV-2 antibody responses in vaccinated long-term care facility staff

Gallichotte

Nehring

Stromberg

et al. 2022

Preprint

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SARS-CoV-2 emerged in 2019 and has resulted in millions of deaths worldwide. Certain populations are at higher risk for infection, especially staff and residents at long term care facilities (LTCF), due to the congregant living setting, and residents with many comorbidities. Prior to vaccine availability, these populations represented a large fraction of total COVID-19 cases and deaths in the U.S. Due to the high-risk setting and outbreak potential, staff and residents were among the first groups to be vaccinated. To define the impact of prior infection on response to vaccination, we measured antibody responses in a cohort of staff members at a LTCF, many of whom were previously infected by SARS-CoV-2. We found that neutralizing, receptor-binding-domain (RBD) and nucleoprotein (NP) binding antibody levels were significantly higher post-full vaccination course in individuals that were previously infected, and NP antibody levels could discriminate individuals with prior infection from vaccinated individuals. While an anticipated antibody titer increase was observed after vaccine booster dose in naïve individuals, boost response was not observed in individuals with previous COVID-19 infection. We observed a strong relationship between neutralizing antibodies and RBD-binding antibodies post-vaccination across all groups, suggesting RBD-binding antibodies may be used as a correlate of neutralization. One individual with high levels of neutralizing and binding antibodies experienced a breakthrough infection (prior to the introduction of Omicron), demonstrating that the presence of antibodies is not always sufficient for complete protection against infection. These results highlight that history of COVID-19 exposure significantly increases SARS-CoV-2 antibody responses following vaccination.ImportanceLong-term care facilities (LTCFs) have been disproportionately impacted by COVID-19, due to their communal nature, high-risk profile of residents and vulnerability to respiratory pathogens. In this study, we analyzed the role of prior natural immunity to SARS-CoV-2 on post-vaccination antibody responses. The LTCF in our cohort experienced a large outbreak with almost 40% of staff becoming infected. We found that individuals that were infected prior to vaccination, had higher levels of neutralizing and binding antibodies post-vaccination. Importantly, the second vaccine dose significantly boosted antibody levels in those that were immunologically naïve prior to vaccination, but not those that had prior immunity. Regardless of pre-vaccination immune status, levels of binding and neutralizing antibodies were highly correlated. The presence of NP-binding antibodies can be used to identify individuals that were previously infected when pre-vaccination immune status is not known. Our results reveal that vaccination antibody responses differ depending on prior natural immunity.

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“…Participants with a positive anti-S IgG concentration at T = 1 (>10.08 BAU/mL) were considered to be previously infected with SARS-CoV-2 and excluded from primary analysis. In case no T = 1 sample was available, a positive anti-N IgG concentration at T = 2 or T = 3 (>14.3 BAU/mL) was also regarded as a possible previous infection and excluded from primary analysis [ 8 ]. Statistical analyses after log-transformation included a Student t test for comparison between the DS cohort and HC cohort and between the administered mRNA vaccines.…”

Section: Methodsmentioning

confidence: 99%

Decreased Antibody Response After Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination in Patients With Down Syndrome

Streng

Bont

Delemarre

et al. 2022

The Journal of Infectious Diseases

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The risk of a severe course of SARS-CoV-2 infection in adults with Down syndrome is increased, resulting in an up to 10-fold increase in mortality, in particular in those over 40 years of age. After primary SARS-CoV-2 vaccination the higher risks remain. In this prospective observational cohort study, SARS-CoV-2 spike S1-specific antibody responses after routine SARS-CoV-2 vaccination (BNT162b2, mRNA-1273 or ChAdOx1) in adults with Down syndrome and healthy controls were compared. Adults with Down syndrome showed lower antibody concentrations after two mRNA vaccinations or after two ChAdOx1 vaccinations. After two mRNA vaccinations lower antibody concentrations were seen with increasing age.

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Seropositivity to Nucleoprotein to detect mild and asymptomatic SARS-CoV-2 infections: A complementary tool to detect breakthrough infections after COVID-19 vaccination?

Cited by 40 publications

References 29 publications

Omicron BA.1 Mutations in SARS-CoV-2 Spike Lead to Reduced T-Cell Response in Vaccinated and Convalescent Individuals

Omicron BA.1 Mutations in SARS-CoV-2 Spike Lead to Reduced T-Cell Response in Vaccinated and Convalescent Individuals

Impact of prior infection on SARS-CoV-2 antibody responses in vaccinated long-term care facility staff

Decreased Antibody Response After Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination in Patients With Down Syndrome

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