Commercial immunoglobulin products contain cross-reactive but not neutralizing antibodies against SARS-CoV-2

Ahn, Terrie S.; Han, Brandon; Krogstad, Paul; Bun, Chantana; Kohn, Lisa A.; Garcia-Lloret, M.; Damoiseaux, Robert; Butte, Manish J.

doi:10.1016/j.jaci.2020.12.003

Cited by 6 publications

(9 citation statements)

References 8 publications

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“…Importantly, this paper associated products with high antibodies titers with donations from countries with a high prevalence of COVID-19 infection and those with low titers produced from countries with low infection rates [148]. Additionally, while the published studies clearly document the emergence of anti-spike SARS-CoV-2 IgG levels [138][139][140][141][142][144][145][146][147][149][150][151][152], in a few cases nucleocapsid-specific IgG was also observed, resulting from natural infection of the donors prior to plasma donation [146,149,152]. This clearly demonstrates the association between geographical location, timing of plasma donations and natural infection and vaccination rates at the time of donation, with the subsequent emergence and levels of SARS-CoV-2 antibody in commercial IgRT.…”

Section: Immunoglobulin Replacement Therapy (Igrt)mentioning

confidence: 97%

“…At the time of printing information regarding SARS-CoV-2-specific antibody content in other countries including Australia was not available. Observational studies showed that products generated from prepandemic plasma contained antibodies cross-reactive to seasonal coronaviruses and SARS-CoV, however none demonstrated the capacity to neutralize the SARS-CoV-2 virus [139][140][141][142][143]. A study by Farcet et al first detected SARS-CoV-2-specific antibodies in product generated from USA donated plasma in September 2020 [144], and Romero et al documented the first positive pools from donations in Spain and the USA in July through September of the same year [145].…”

Section: Immunoglobulin Replacement Therapy (Igrt)mentioning

confidence: 99%

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An Overview of the Immune Response to COVID-19 Vaccination and Strategies to Boost SARS-CoV-2 Immunity in People with Inborn Errors of Immunity

Chang-Rabley,

van Zelm,

Ricotta

et al. 2024

Preprint

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The ongoing SARS-CoV-2 pandemic has raised concerns surrounding immunological protection against the virus, particularly for people with inborn errors of immunity (IEI). While COVID-19 vaccination induces robust antibody, memory B-cell, and T-cell responses in healthy individuals, how well vaccination protects people with IEI against infection and severe disease remains unclear – especially in the context of new viral variants and vaccine formulations – leading to anxiety, ongoing self-isolation, and repeated vaccination with limited evidence of increased efficacy. Whilst most people with IEI generate some level of cellular and/or humoral immunity to COVID-19 vaccination, the level of protection and durability of the response are unclear. Alongside vaccination, antibody-based therapeutics are aimed at limiting infection and severe disease in this cohort. Immunoglobulin replacement therapy (IgRT) provides passive immunity in antibody-deficient individuals. However, to successfully prevent SARS-CoV-2 infection, a sufficient number of neutralizing antibodies must be present in product. While antibodies against circulating variants are eventually present in IgRT products (both from natural infection and vaccination of the donors), evidence of their capacity to recognize new variants is limited. Furthermore, while antibody-based pre- and post-exposure prophylaxis can be effective, they are susceptible to decreased efficacy in the context of variant evolution. This review provides an in-depth overview of current knowledge about COVID-19 vaccine efficacy in IEIs, the efficacy of SARS-CoV-2-specific antibody products, and knowledge and technological advances required for continued protection of people with IEI.

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Section: Immunoglobulin Replacement Therapy (Igrt)mentioning

confidence: 97%

Section: Immunoglobulin Replacement Therapy (Igrt)mentioning

confidence: 99%

An Overview of the Immune Response to COVID-19 Vaccination and Strategies to Boost SARS-CoV-2 Immunity in People with Inborn Errors of Immunity

Chang-Rabley,

van Zelm,

Ricotta

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Commercial immunoglobulin preparations do not usually contain neutralizing antibodies to SARS-CoV-2 [ 119 ] and hence, all patients with combined immunodeficiency should receive SARS-CoV-2 vaccine, apart from continuing to use protective measures like masking. No serious adverse effects have been reported among patients who have received SARS-CoV-2 vaccine and studies on development of protective immunity have showed encouraging results [ 120 , 121 , 122 ].…”

Section: Preventive Measuresmentioning

confidence: 99%

“…Combined immunodeficiency with multiple atresias involving gastrointestinal tract extending from pylorus to rectum was first described in 1990 [ 119 ]. Most cases are sporadic, but autosomal recessive inheritance has also been described.…”

Section: Other Defectsmentioning

confidence: 99%

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Infections in Inborn Errors of Immunity with Combined Immune Deficiency: A Review

George

Govindaraj

2023

Pathogens

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Enhanced susceptibility to microbes, often resulting in severe, intractable and frequent infections due to usually innocuous organisms at uncommon sites, is the most striking feature in individuals with an inborn error of immunity. In this narrative review, based on the International Union of Immunological Societies’ 2022 (IUIS 2022) Update on phenotypic classification of human inborn errors of immunity, the focus is on commonly encountered Combined Immunodeficiency Disorders (CIDs) with susceptibility to infections. Combined immune deficiency disorders are usually commensurate with survival beyond infancy unlike Severe Combined Immune Deficiency (SCID) and are often associated with clinical features of a syndromic nature. Defective humoral and cellular immune responses result in susceptibility to a broad range of microbial infections. Although disease onset is usually in early childhood, mild defects may present in late childhood or even in adulthood. A precise diagnosis is imperative not only for determining management strategies, but also for providing accurate genetic counseling, including prenatal diagnosis, and also in deciding empiric treatment of infections upfront before investigation reports are available.

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Neutralizing SARS-CoV-2 Antibodies in Commercial Immunoglobulin Products Give Patients with X-Linked Agammaglobulinemia Limited Passive Immunity to the Omicron Variant

et al. 2022

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Immunodeficient individuals often rely on donor-derived immunoglobulin (Ig) replacement therapy (IGRT) to prevent infections. The passive immunity obtained by IGRT is limited and reflects the state of immunity in the plasma donor population at the time of donation. The objective of the current study was to describe how the potential of passive immunity to SARS-CoV-2 in commercial off-the-shelf Ig products used for IGRT has evolved during the pandemic. Samples were collected from all consecutive Ig batches (n = 60) from three Ig producers used at the Immunodeficiency Unit at Karolinska University Hospital from the start of the SARS-CoV-2 pandemic until January 2022. SARS-CoV-2 antibody concentrations and neutralizing capacity were assessed in all samples. In vivo relevance was assessed by sampling patients with XLA (n = 4), lacking endogenous immunoglobulin synthesis and on continuous Ig substitution, for plasma SARS-CoV-2 antibody concentration. SARS-CoV-2 antibody concentrations in commercial Ig products increased over time but remained inconsistently present. Moreover, Ig batches with high neutralizing capacity towards the Wuhan-strain of SARS-CoV-2 had 32-fold lower activity against the Omicron variant. Despite increasing SARS-CoV-2 antibody concentrations in commercial Ig products, four XLA patients on IGRT had relatively low plasma concentrations of SARS-CoV-2 antibodies with no potential to neutralize the Omicron variant in vitro. In line with this observation, three out the four XLA patients had symptomatic COVID-19 during the Omicron wave. In conclusion, 2 years into the pandemic the amounts of antibodies to SARS-CoV-2 vary considerably among commercial Ig batches obtained from three commercial producers. Importantly, in batches with high concentrations of antibodies directed against the original virus strain, protective passive immunity to the Omicron variant appears to be insufficient.

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Commercial immunoglobulin products contain cross-reactive but not neutralizing antibodies against SARS-CoV-2

Cited by 6 publications

References 8 publications

An Overview of the Immune Response to COVID-19 Vaccination and Strategies to Boost SARS-CoV-2 Immunity in People with Inborn Errors of Immunity

An Overview of the Immune Response to COVID-19 Vaccination and Strategies to Boost SARS-CoV-2 Immunity in People with Inborn Errors of Immunity

Infections in Inborn Errors of Immunity with Combined Immune Deficiency: A Review

Neutralizing SARS-CoV-2 Antibodies in Commercial Immunoglobulin Products Give Patients with X-Linked Agammaglobulinemia Limited Passive Immunity to the Omicron Variant

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