Vaccination prevents severe COVID-19 outcome in patients with neutralizing type 1 interferon autoantibodies

Wolff, Anette S. B.; Hansen, Lena; Grytaas, Marianne Aa.; Oftedal, Bergithe E.; Breivik, Lars; Zhou, Fan; Hufthammer, Karl Ove; Sjøgren, Thea; Olofsson, Jan; Trieu, Mai-Chi; Meager, Anthony; Jørgensen, Anders Palmstrøm; Lima, Kari; Mohn, Kristin Greve-Isdahl; Langeland, Nina; Husebye, Eystein S.

doi:10.1016/j.isci.2023.107084

Cited by 4 publications

(2 citation statements)

References 55 publications

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“…For instance, recent reports have suggested that autoantibodies targeting type I IFNs develop after vaccination with mRNA SARS-CoV-2 vaccines but not with viral vector-based vaccines [ 49 , 50 ]. While these autoantibodies have been associated with adverse reactions in other vaccines such as the live-attenuated yellow vaccine [ 51 ], such an association has not been observed in SARS-CoV-2 vaccines [ 52 , 53 ].…”

Section: Discussionmentioning

confidence: 99%

Association between Reactogenicity and Immunogenicity in a Vaccinated Cohort with Two mRNA SARS-CoV-2 Vaccines at a High-Complexity Reference Hospital: A Post Hoc Analysis on Immunology Aspects of a Prospective Cohort Study

Sáez-Peñataro,

Calvo,

Bascuas

et al. 2024

Vaccines

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Enhancing our comprehension of mRNA vaccines may facilitate the future design of novel vaccines aimed at augmenting immune protection while minimising reactogenic responses. Before this design is carried out, it is important to determine whether adaptive immunity correlates with the reactogenicity profile of vaccines. We studied a large cohort that was vaccinated with mRNA vaccines to answer this question. This was an observational study with real-world data. Reactogenicity data were obtained from the VigilVacCOVID study. Immunogenicity (humoral and cellular) data were retrieved from health records. One main population (n = 215) and two subpopulations were defined (subpopulation 1, n = 3563; subpopulation 2, n = 597). Sensitivity analyses were performed with subpopulations 1 and 2 to explore the consistency of results. We analysed the association of the intensity and types of adverse reactions with the development and quantity of elicited antibody titres. As an exploratory analysis in subpopulation 1, we assessed the association between reactogenicity and cellular immunogenicity. A higher incidence of fever, malaise, and myalgia including severe cases was significantly associated with the development and quantity of positive antibody titres. No significant findings were observed with cellular immunity. We observed a positive association between immunogenicity and reactogenicity. These findings can be relevant for the future development of our understanding of how mRNA vaccines function.

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Section: Discussionmentioning

confidence: 99%

Association between Reactogenicity and Immunogenicity in a Vaccinated Cohort with Two mRNA SARS-CoV-2 Vaccines at a High-Complexity Reference Hospital: A Post Hoc Analysis on Immunology Aspects of a Prospective Cohort Study

Sáez-Peñataro,

Calvo,

Bascuas

et al. 2024

Vaccines

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“…Pre-existing IFN-I autoAbs was the common denominator and it was established that the viral defense was affected in these patients. Although the severity of COVID-19 disease in APS-I has later been challenged ( 139 , 140 ), perhaps as a consequence of evolving virus variants and/or vaccination, the fact that individuals with anti-IFN-I autoAbs are at risk of severe lung manifestations still stands. This is supported by the presence of high levels of neutralizing IFN-I autoAbs in about 10% of patients across different age groups suffering from life-threatening COVID-19 ( 34 , 137 ).…”

Section: Recognized Physiologic Roles Of Autoabs To Ifn-ismentioning

confidence: 99%

Interferon autoantibodies as signals of a sick thymus

Oftedal,

Sjøgren,

Wolff

2024

Front. Immunol.

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Type I interferons (IFN-I) are key immune messenger molecules that play an important role in viral defense. They act as a bridge between microbe sensing, immune function magnitude, and adaptive immunity to fight infections, and they must therefore be tightly regulated. It has become increasingly evident that thymic irregularities and mutations in immune genes affecting thymic tolerance can lead to the production of IFN-I autoantibodies (autoAbs). Whether these biomarkers affect the immune system or tissue integrity of the host is still controversial, but new data show that IFN-I autoAbs may increase susceptibility to severe disease caused by certain viruses, including SARS-CoV-2, herpes zoster, and varicella pneumonia. In this article, we will elaborate on disorders that have been identified with IFN-I autoAbs, discuss models of how tolerance to IFN-Is is lost, and explain the consequences for the host.

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Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

Bastard,

Gervais,

Taniguchi

et al. 2024

Journal of Experimental Medicine

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We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-α2 in 10 patients: IFN-α2 only in three, IFN-α2 plus IFN-ω in five, and IFN-α2, IFN-ω plus IFN-β in two; IFN-ω only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-α2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-ω in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-α2 only (OR [95% CI] = 67.6 [5.7–9,196.6]) than for auto-Abs neutralizing IFN-ω only (OR [95% CI] = 2.6 [1.2–5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6–35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1–9.6]) of IFN-ω and/or IFN-α2.

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Vaccination prevents severe COVID-19 outcome in patients with neutralizing type 1 interferon autoantibodies

Cited by 4 publications

References 55 publications

Association between Reactogenicity and Immunogenicity in a Vaccinated Cohort with Two mRNA SARS-CoV-2 Vaccines at a High-Complexity Reference Hospital: A Post Hoc Analysis on Immunology Aspects of a Prospective Cohort Study

Association between Reactogenicity and Immunogenicity in a Vaccinated Cohort with Two mRNA SARS-CoV-2 Vaccines at a High-Complexity Reference Hospital: A Post Hoc Analysis on Immunology Aspects of a Prospective Cohort Study

Interferon autoantibodies as signals of a sick thymus

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

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