Neutralizing antibody responses 300 days after SARS‐CoV‐2 infection and induction of high antibody titers after vaccination

Urlaub, Doris; Wolfsdorff, Natalie; Hoffmann, Jan‐Erik; Dorok, Stefanie; Hoffmann, Markus; Anft, Moritz; Pieris, Naomi; Günther, Patrick; Schaaf, Bernhard; Cassens, U.; Bröde, Peter; Claus, Maren; Picard, Lea Katharina; Wingert, Sabine; Backes, Simone; Durak, Deniz; Babel, Nina; Pöhlmann, Stefan; Renken, Frank; Raunser, Stefan; Watzl, Carsten

doi:10.1002/eji.202149758

Cited by 9 publications

(11 citation statements)

References 24 publications

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“…Human and NHP studies of adults have documented the decline of nAb after SARS-CoV-2 vaccination or infection ( 18 , 25 , 44 – 46 ). Our knowledge about the durability of SARS-CoV-2 immune responses in infants and children, however, is still limited ( 47 , 48 ).…”

Section: Discussionmentioning

confidence: 99%

Infant rhesus macaques immunized against SARS-CoV-2 are protected against heterologous virus challenge 1 year later

et al. 2023

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The U.S. Food and Drug Administration only gave emergency-use-authorization of the BNT162b2 and the mRNA-1273 SARS-CoV-2 vaccines for infants 6 months and older in June 2022. Yet, questions regarding the durability of vaccine efficacy, especially against emerging variants, in this age group remain. We demonstrated previously that a two-dose regimen of stabilized prefusion Washington SARS-CoV-2 S-2P spike (S) protein encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or purified S-2P mixed with 3 M-052, a synthetic toll-like receptor (TLR) 7/8 agonist, in a squalene emulsion (Protein+3 M-052-SE) was safe and immunogenic in infant rhesus macaques. Here, we demonstrate that broadly neutralizing and spike-binding antibodies against variants of concern (VOC), as well as T cell responses, persisted for 12 months. At one year, corresponding to human toddler age, we challenged vaccinated rhesus macaques and age-matched non-vaccinated controls intranasally and intratracheally with a high-dose of heterologous SARS-CoV-2 B.1.617.2 (Delta). Seven of eight control rhesus macaques exhibited severe interstitial pneumonia and high virus replication in the upper and lower respiratory tract. In contrast, vaccinated rhesus macaques had faster viral clearance with mild to no pneumonia. Neutralizing and binding antibody responses to the B.1.617.2 variant at the day of challenge correlated with lung pathology and reduced virus replication. Overall, the Protein+3 M-052-SE vaccine provided superior protection to the mRNA-LNP vaccine, emphasizing opportunities for optimization of current vaccine platforms. Notably, the observed efficacy of both vaccines one year after vaccination supports the implementation of an early life SARS-CoV-2 vaccine.

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Section: Discussionmentioning

confidence: 99%

Infant rhesus macaques immunized against SARS-CoV-2 are protected against heterologous virus challenge 1 year later

et al. 2023

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“…The enzyme-linked immunosorbent assay for determination of anti-SARS-CoV-2 spike antibody titers was conducted as described before ( 6 ). Briefly, the RBD sequence (spike glycoprotein amino acids 319–541) of the Wuhan strain of SARS-CoV-2 with a C-terminal HIS-tag was expressed in HEK 293-F cells and purified on a HisTrap Excel column using an ÄKTAxpress purification system.…”

Section: Methodsmentioning

confidence: 99%

“…HRP conjugated anti-human IgG (Dianova) was used as secondary antibody. Antibody titers were calculated as BAU/ml and values higher than 30.3 were considered as positive ( 6 ).…”

Section: Methodsmentioning

confidence: 99%

Immune response in ofatumumab treated multiple sclerosis patients after SARS-CoV-2 vaccination

Faissner

Heitmann²,

Plaza-Sirvent³

et al. 2022

Front. Immunol.

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ObjectiveThe pandemic induced by SARS-CoV-2 has huge implications for patients with immunosuppression that is caused by disorders or specific treatments. Especially approaches targeting B cells via anti-CD20 therapy are associated with impaired humoral immune response but sustained cellular immunity. Ofatumumab is a human anti-CD20 directed antibody applied in low dosages subcutaneously, recently licensed for Multiple Sclerosis (MS). Effects of early ofatumumab treatment on alterations of immune cell composition and immune response towards SARS-CoV-2 are incompletely understood.MethodsWe here investigated immune cell alterations in early ofatumumab (Ofa) treated patients and effects on humoral (titer, neutralization capacity against wild type, Delta and Omicron) and cellular immune responses in Ofa treated MS patients following a third vaccination against SARS-CoV-2 compared to healthy controls.ResultsWe show that a mean treatment duration of three months in the Ofa group led to near complete B cell depletion in line with altered composition of certain CD4+ T cell subpopulations such as enhanced frequencies of naive and a decrease of non-suppressive regulatory T cells (Tregs). Titer and neutralization capacity against SARS-CoV-2 variants was impaired while cellular immune response was sustained, characterized by a strong T helper 1 profile (Th1).InterpretationIn summary, low dosage ofatumumab treatment elicits sustained depletion of B cells in line with alterations of immune cells, mainly Tregs. This is associated with impaired humoral immune response towards SARS-CoV-2 vaccination but preserved, Th1 driven cellular immunity adding crucial information regarding early effects of low dosage anti-CD20 therapy on humoral and cellular immunity.

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“…Binding antibody units (BAU/mL) against the receptor binding domain (RBD) of the SARS-CoV-2 Spike from the Wuhan strain amongst the groups were measured as previously described ( 36 ). Briefly, 96 well plates were coated with recombinant RBD of SARS-CoV-2 WT spike overnight at 4°C and subsequently blocked with ELISA Diluent (Biolegend) for 1 h at 37 °C.…”

Section: Methodsmentioning

confidence: 99%

In-depth analysis of T cell immunity and antibody responses in heterologous prime-boost-boost vaccine regimens against SARS-CoV-2 and Omicron variant

et al. 2022

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With the emergence of novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Variants of Concern (VOCs), vaccination studies that elucidate the efficiency and effectiveness of a vaccination campaign are critical to assess the durability and the protective immunity provided by vaccines. SARS-CoV-2 vaccines have been found to induce robust humoral and cell-mediated immunity in individuals vaccinated with homologous vaccination regimens. Recent studies also suggest improved immune response against SARS-CoV-2 when heterologous vaccination strategies are employed. Yet, few data exist on the extent to which heterologous prime-boost-boost vaccinations with two different vaccine platforms have an impact on the T cell-mediated immune responses with a special emphasis on the currently dominantly circulating Omicron strain. In this study, we collected serum and peripheral blood mononuclear cells (PBMCs) from 57 study participants of median 35-year old’s working in the health care field, who have received different vaccination regimens. Neutralization assays revealed robust but decreased neutralization of Omicron VOC, including BA.1 and BA.4/5, compared to WT SARS-CoV-2 in all vaccine groups and increased WT SARS-CoV-2 binding and neutralizing antibodies titers in homologous mRNA prime-boost-boost study participants. By investigating cytokine production, we found that homologous and heterologous prime-boost-boost-vaccination induces a robust cytokine response of CD4+ and CD8+ T cells. Collectively, our results indicate robust humoral and T cell mediated immunity against Omicron in homologous and heterologous prime-boost-boost vaccinated study participants, which might serve as a guide for policy decisions.

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Neutralizing antibody responses 300 days after SARS‐CoV‐2 infection and induction of high antibody titers after vaccination

Cited by 9 publications

References 24 publications

Infant rhesus macaques immunized against SARS-CoV-2 are protected against heterologous virus challenge 1 year later

Infant rhesus macaques immunized against SARS-CoV-2 are protected against heterologous virus challenge 1 year later

Immune response in ofatumumab treated multiple sclerosis patients after SARS-CoV-2 vaccination

In-depth analysis of T cell immunity and antibody responses in heterologous prime-boost-boost vaccine regimens against SARS-CoV-2 and Omicron variant

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