Immune Response in Moderate to Critical Breakthrough COVID-19 Infection After mRNA Vaccination

Paniskaki, Krystallenia; Anft, Moritz; Meister, Toni Luise; Marheinecke, Corinna; Pfaender, Stephanie; Skrzypczyk, Sarah; Seibert, Felix S.; Thieme, Constantin J.; Konik, Margarethe; Dolff, Sebastian; Anastasiou, Olympia E.; Hölzer, Bodo; Dittmer, Ulf; Queren, Christine; Fricke, Lutz; Rohn, Hana; Westhoff, Timm H.; Witzke, Oliver; Stervbo, Ulrik; Roch, Toralf; Babel, Nina

doi:10.3389/fimmu.2022.816220

Cited by 25 publications

(33 citation statements)

References 44 publications

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“…Neutralizing and binding antibody levels are being developed as correlates of protection, as they are highly correlated with vaccine efficacy across diverse cohorts and vaccine platforms [27][28][29]. There are reports describing breakthrough infections post-vaccination, likely due to reduced/waning antibody levels and timing post-vaccination [30][31][32][33]. The breakthrough infection that occurred in our cohort, was in an individual with high neutralizing antibody levels similar to other recent reports [34,35].…”

Section: Discussionsupporting

confidence: 82%

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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Section: Discussionsupporting

confidence: 82%

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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show abstract

“…In addition, for patients with certain MHC genotypes, immune responses might be mainly directed against SARS-CoV-2 proteins other than the S protein, such as the M or N protein. In such patients, S-protein-based immunization might not elicit an immune response capable of preventing a breakthrough infection 174 .…”

Section: Discussionmentioning

confidence: 99%

Vaccination in patients with kidney failure: lessons from COVID-19

2022

Self Cite

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Infection is the second leading cause of death in patients with chronic kidney disease (CKD). Adequate humoral (antibody) and cellular (T cell-driven) immunity are required to minimize pathogen entry and promote pathogen clearance to enable infection control. Vaccination can generate cellular and humoral immunity against specific pathogens and is used to prevent many life-threatening infectious diseases. However, vaccination efficacy is diminished in patients with CKD. Premature ageing of the immune system and chronic systemic low-grade inflammation are the main causes of immune alteration in these patients. In the case of SARS-CoV-2 infection, COVID-19 can have considerable detrimental effects in patients with CKD, especially in those with kidney failure. COVID-19 prevention through successful vaccination is therefore paramount in this vulnerable population. Although patients receiving dialysis have seroconversion rates comparable to those of patients with normal kidney function, most kidney transplant recipients could not generate humoral immunity after two doses of the COVID-19 vaccine. Importantly, some patients who were not able to produce antibodies still had a detectable vaccine-specific T cell response, which might be sufficient to prevent severe COVID-19. Correlates of protection against SARS-CoV-2 have not been established for patients with kidney failure, but they are urgently needed to enable personalized vaccination regimens.

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“…Breakthrough infections with the Alpha variant in fully vaccinated individuals have been associated with lower titers of neutralizing antibodies (20)(21)(22) and less robust T cell responses (23). However, given that the Omicron variant has more mutations and evades neutralizing antibody responses better than prior VOCs, the mechanisms of Omicron variant breakthrough infections are likely different.…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2–specific immune responses in boosted vaccine recipients with breakthrough infections during the Omicron variant surge

Woldemeskel¹,

Garliss²,

Aytenfisu³

et al. 2022

JCI Insight

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Immune Response in Moderate to Critical Breakthrough COVID-19 Infection After mRNA Vaccination

Cited by 25 publications

References 44 publications

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

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

Vaccination in patients with kidney failure: lessons from COVID-19

SARS-CoV-2–specific immune responses in boosted vaccine recipients with breakthrough infections during the Omicron variant surge

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