<scp>Neutralizing antibody levels against SARS‐CoV</scp>‐2 <scp>variants of concern Delta and Omicron in vaccine breakthrough‐infected blood donors</scp>

Franchini, Massimo; Focosi, Daniele; Mengoli, Carlo; Percivalle, Elena; Sammartino, José Camilla; Ferrari, Alessandro; Zani, Matteo; Glingani, Claudia; Baldanti, Fausto

doi:10.1111/trf.16887

Cited by 5 publications

(4 citation statements)

References 20 publications

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“…These results together support our approach that identifying biologically functional and conserved epitopes based on immuno-bioinformatics induces the production of neutralizing antibodies, which has been confirmed by our group several times ( 9 – 11 , 61 , 62 ). Thus, these results demonstrate that the multiepitope chimeric protein could potentially provide protection against the SARS-CoV-2 VOC evaluated here, albeit the neutralizing capacity appears to be dose-dependent and varies among the different viral strains, as shown here and in other works ( 63 , 64 ). In this work, we did not test neutralization against any omicron subvariants, which appeared after we performed the experiments.…”

Section: Discussionsupporting

confidence: 83%

Evaluation of the humoral and mucosal immune response of a multiepitope vaccine against COVID-19 in pigs

Mosqueda,

Hernández-Silva,

Vega-López

et al. 2023

Front. Immunol.

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IntroductionThis study evaluated the immune response to a multiepitope recombinant chimeric protein (CHIVAX) containing B- and T-cell epitopes of the SARS-CoV-2 spike’s receptor binding domain (RBD) in a translational porcine model for pre-clinical studies.MethodsWe generated a multiepitope recombinant protein engineered to include six coding conserved epitopes from the RBD domain of the SARS-CoV-2 S protein. Pigs were divided into groups and immunized with different doses of the protein, with serum samples collected over time to determine antibody responses by indirect ELISA and antibody titration. Peptide recognition was also analyzed by Western blotting. A surrogate neutralization assay with recombinant ACE2 and RBDs was performed. Intranasal doses of the immunogen were also prepared and tested on Vietnamese minipigs.ResultsWhen the immunogen was administered subcutaneously, it induced specific IgG antibodies in pigs, and higher doses correlated with higher antibody levels. Antibodies from immunized pigs recognized individual peptides in the multiepitope vaccine and inhibited RBD-ACE2 binding for five variants of concern (VOC). Comparative antigen delivery methods showed that both, subcutaneous and combined subcutaneous/intranasal approaches, induced specific IgG and IgA antibodies, with the subcutaneous approach having superior neutralizing activity. CHIVAX elicited systemic immunity, evidenced by specific IgG antibodies in the serum, and local mucosal immunity, indicated by IgA antibodies in saliva, nasal, and bronchoalveolar lavage secretions. Importantly, these antibodies demonstrated neutralizing activity against SARS-CoV-2 in vitro.DiscussionThe elicited antibodies recognized individual epitopes on the chimeric protein and demonstrated the capacity to block RBD-ACE2 binding of the ancestral SARS-CoV-2 strain and four VOCs. The findings provide proof of concept for using multiepitope recombinant antigens and a combined immunization protocol to induce a neutralizing immune response against SARS-CoV-2 in the pig translational model for preclinical studies.

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Section: Discussionsupporting

confidence: 83%

Evaluation of the humoral and mucosal immune response of a multiepitope vaccine against COVID-19 in pigs

Mosqueda,

Hernández-Silva,

Vega-López

et al. 2023

Front. Immunol.

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“…Many more inactivated vaccines have been in use in low-and-middle-income countries (LMIC), which are target regions for CCP therapy: this is feasible given the lower number of patients at risk for disease progression there (lower incidences of obesity, diabetes, and hypertension, and lower median age) and the already widespread occurrence of collection and transfusion facilities. Most blood donors there have already received the vaccine schedule before, after, or without having been infected, with a nAb titer generally declining over months 12 . Hence identifying the settings where the nAb titer is highest will definitively increase the efficacy of CCP collections.…”

Section: Introductionmentioning

confidence: 99%

Analysis of anti-SARS-CoV-2 Omicron-neutralizing antibody titers in different vaccinated and unvaccinated convalescent plasma sources

et al. 2022

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The latest SARS-CoV-2 variant of concern Omicron, with its immune escape from therapeutic anti-Spike monoclonal antibodies and WA-1 vaccine-elicited sera, demonstrates the continued relevance of COVID-19 convalescent plasma (CCP) therapies. Lessons learnt from previous usage of CCP suggests focusing on early outpatients and immunocompromised recipients, with high neutralizing antibody titer units. Here, we systematically review Omicron-neutralizing plasma activity data, and report that approximately 47% (424/902) of CCP samples from unvaccinated pre-Omicron donors neutralizes Omicron BA.1 with a very low geometric mean of geometric mean titers for 50% neutralization GM(GMT50) of ~13, representing a > 20-fold reduction from WA-1 neutralization. Non-convalescent subjects who had received two doses of mRNA vaccines had a GM(GMT50) for Omicron BA.1 neutralization of ~27. However, plasma from vaccinees recovering from either previous pre-Omicron variants of concern infection, Omicron BA.1 infection, or third-dose uninfected vaccinees was nearly 100% neutralizing against Omicron BA.1, BA.2 and BA.4/5 with GM(GMT(50)) all over 189, 10 times higher than pre-Omicron CCP. Fully vaccinated and post-BA.1 plasma (Vax-CCP) had a GM(GMT50) > 450 for BA.4/5 and >1,500 for BA.1 and BA.2. These findings have implications for both CCP stocks collected in prior pandemic periods and for future plans to restart CCP collections. Thus, Vax-CCP provides an effective tool to combat ongoing variants that escape therapeutic monoclonal antibodies.

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“…Indeed, clinicians once again found themselves without an effective and specific anti-viral therapy for their patients, particularly for those not able to mount a sufficient anti-viral immune response. To meet the increasing CCP demands, we reorganized CCP collection using the best literature evidence to produce CCP with the highest nAb titer; thus, we recruited local regular blood donors that were both COVID-19 vaccinated and recently recovered from SARS-CoV-2 infection [ 25 , 26 ]. In addition, to give the maximum anti-viral effect, we transfused CCP units titered against patients’ VOCs and the Italian reference SARS-CoV-2 strain PV10734.…”

Section: Discussionmentioning

confidence: 99%

Variant of Concern-Matched COVID-19 Convalescent Plasma Usage in Seronegative Hospitalized Patients

Franchini

Focosi²,

Percivalle

et al. 2022

Viruses

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COVID-19 convalescent plasma (CCP) has been the only specific anti-viral therapy against SARS-CoV-2 available for more than one year. Following the negative results from most randomized controlled trials on its efficacy in COVID-19 hospitalized patients and the availability of anti-spike monoclonal antibodies (mAbs), the use of CCP has subsequently rapidly faded. However, the continuous appearance of new variants of concern (VOCs), most of which escape mAbs and vaccine-elicited neutralizing antibodies (nAbs), has renewed the interest towards CCP, at least in seronegative immunocompetent patients, and in immunocompromised patients not able to mount a protective immune response. We report here the experience of a single Italian hospital in collecting and transfusing CCP in immunocompromised patients hospitalized for severe COVID-19 between October 2021 and March 2022. During this 6-month period, we collected CCP from 32 vaccinated and convalescent regular blood donors, and infused high nAb-titer CCP units (titered against the specific VOC affecting the recipient) to 21 hospitalized patients with severe COVID-19, all of them seronegative at the time of CCP transfusion. Patients’ median age was 66 years (IQR 50–74 years) and approximately half of them (47.6%, 10/21) were immunocompromised. Two patients were rescued after previous failure of mAbs. No adverse reactions following CCP transfusion were recorded. A 28-day mortality rate of 14.3 percent (3/21) was reported, with age, advanced disease stage and late CCP transfusion associated with a worse outcome. This real-life experience also supports the use of CCP in seronegative hospitalized COVID-19 patients during the Delta and Omicron waves.

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Neutralizing antibody levels against SARS‐CoV‐2 variants of concern Delta and Omicron in vaccine breakthrough‐infected blood donors

Cited by 5 publications

References 20 publications

Evaluation of the humoral and mucosal immune response of a multiepitope vaccine against COVID-19 in pigs

Evaluation of the humoral and mucosal immune response of a multiepitope vaccine against COVID-19 in pigs

Analysis of anti-SARS-CoV-2 Omicron-neutralizing antibody titers in different vaccinated and unvaccinated convalescent plasma sources

Variant of Concern-Matched COVID-19 Convalescent Plasma Usage in Seronegative Hospitalized Patients

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