{"id":8313,"date":"2023-11-22T06:00:00","date_gmt":"2023-11-22T11:00:00","guid":{"rendered":"http:\/\/www.cov19longhaulfoundation.org\/?p=8313"},"modified":"2023-11-22T06:00:00","modified_gmt":"2023-11-22T11:00:00","slug":"therapeutic-potential-of-convalescent-plasma-and-hyperimmune-immunoglobulins-against-sars-cov-2-bq-1-bq-1-1-and-xbb-variants","status":"publish","type":"post","link":"https:\/\/cov19longhaulfoundation.org\/?p=8313","title":{"rendered":"Therapeutic potential of convalescent plasma and hyperimmune immunoglobulins against SARS-CoV-2 BQ.1, BQ.1.1, and XBB variants"},"content":{"rendered":"\n

Lorenza Bellusci,\u00a0Hana Golding, and\u00a0Surender Khurana Journal of Clinical Investigation<\/h4>\n\n\n\n

Published 2023 – More info<\/a>View PDF <\/a><\/p>\n\n\n\n

Convalescent plasma (CP) and hyperimmune intravenous immunoglobulins (IVIGs) are routinely used to treat patients with COVID-19. SARS-CoV-2 Omicron variants continue to evolve, generating multiple sublineages with increased transmissibility and antibody-escape mutations (1<\/a>, 2<\/a>). Several Omicron lineages that are currently circulating (BA.4, BA.5, BA.2.75, BA.2.75.2, BQ.1, BQ.1.1, and recombinant XBB) contain many mutations in spike protein (Supplemental Table 1<\/a>; supplemental material available online with this article; https:\/\/doi.org\/10.1172\/JCI168583DS1<\/a>), resulting in resistance to most therapeutic monoclonal antibodies as well as antibodies generated by SARS-CoV-2 vaccines (1<\/a>, 2<\/a>).<\/p>\n\n\n\n

Hyperimmune anti\u2013SARS-CoV-2 IVIGs (hCoV-2IG) have been manufactured from pooled plasma units of hundred to thousands of convalescent individuals. hCoV-2IG contain immunoglobulin G at a 10-fold higher concentration compared with that in CP, and they are being evaluated for treatment of COVID-19 (3<\/a>).<\/p>\n\n\n\n

To evaluate their therapeutic potential, 19 lots of hCoV-2IG prepared from convalescent individuals infected with SARS-CoV-2 in 2020, prior to circulation of Omicron; 20 IVIG preparations manufactured in 2019 (2019-IVIG) before the COVID-19 pandemic; and 8 IVIG lots manufactured from healthy plasma donations in 2020 (2020-IVIG) were analyzed for neutralization of SARS-CoV-2 Omicron BA.4\/BA.5, BA.2.75, BA.2.75.2, BQ.1, BQ.1.1, and XBB subvariants in a pseudovirus neutralization assay (PsVNA) (Supplemental Methods<\/a>). For comparison, we evaluated 8 CP samples from recovered patients with COVID-19 in early 2020 (2020-CP) and 9 CP samples from Omicron vaccine-breakthrough infections in 2022 (2022-CP).<\/p>\n\n\n\n

2020-CP showed variable PsVNA50 titers against WA-1, ranging between 10 and 1,343 (geometric mean titer [GMT]: 154), but did not neutralize BQ.1, BQ.1.1, or XBB (Figure 1A<\/a> and Supplemental Table 2<\/a>). In contrast, 2022-CP demonstrated robust PsVNA50 titers against WA-1 (GMT: 926) and most neutralized BA.2.75, BA.2.75.2, and BA.4\/BA.5 (GMT: 50, 59, and 71, respectively). However, only 4 2022-CP showed low neutralization of BQ.1 (GMT: 25), BQ.1.1 (GMT: 22), and XBB (GMT: 21).<\/a><\/p>\n\n\n\n

<\/a>Figure 1<\/a><\/p>\n\n\n\n

\"\"<\/figure>\n\n\n\n

Neutralization of SARS-CoV-2 WA-1\/2020 strain and Omicron subvariants by IVIG, convalescent plasma, and hCoV-2IG.<\/strong> (A<\/strong>) SARS-CoV-2 neutralization assays were performed using pseudoviruses expressing the spike protein of WA-1\/2020 or the Omicron subvariants in 293-ACE2-TMPRSS2 cells. SARS-CoV-2 neutralization titers were determined in each of the prepandemic 2019-IVIG (n<\/em> = 20; black), 2020-IVIG (n<\/em> = 8; pink), 2020 convalescent plasma (2020-CP; n<\/em> = 8; blue), 2022 convalescent plasma (2022-CP; n<\/em> = 9; turquoise), and hCoV-2IG (n<\/em> = 19; red) preparations. The assay was performed in duplicate to determine the 50% neutralization titer (PsVNA50). The heights of the bars and the numbers over the bars indicate the geometric mean titers, and the whiskers indicate 95% CIs. The horizontal dashed line indicates the limit of detection for the neutralization assay (PsVNA50 of 20). Differences between SARS-CoV-2 strains were analyzed by ordinary 1-way ANOVA, using Tukey\u2019s pairwise multiple-comparison test in GraphPad Prism version 9.3.1, and P<\/em> values are shown. (B<\/strong>) Relationship of neutralizing antibodies against SARS-CoV-2 WA-1\/2020 and Omicron subvariants. Correlation of SARS-CoV-2 WA-1\/2020 neutralizing titer versus Omicron subvariant neutralizing titer for 2020-CP (n<\/em> = 8; blue), 2022-CP (n<\/em> = 9; turquoise), and hCoV-2IG (n<\/em> = 19; red). Correlations show Pearson\u2019s correlation coefficient (r<\/em>) and 2-tailed P<\/em> values for all samples. The black lines in the scatter plots depict the linear fit of log2<\/sub>-transformed PsVNA50 values, with shaded area showing 95% CI.<\/p>\n\n\n\n

As expected, the 2019-IVIG lots did not neutralize any SARS-CoV-2 strain. The 2020-IVIG lots (made from plasma units that were not screened for anti\u2013SARS-CoV-2 neutralizing antibodies) had low PsVNA50 titers against WA-1 (GMT: 35) and did not neutralize Omicron variants (Figure 1A<\/a> and Supplemental Table 2<\/a>).<\/p>\n\n\n\n

The 19 hCoV-2IG lots demonstrated robust neutralization of WA-1 (GMT: 1,615) (Figure 1A<\/a>). Surprisingly, all 19 lots exhibited neutralization titers against BA.4\/BA.5, ranging from 47 to 205 (GMT: 83). Importantly, 15 of the 19 hCoV-2IG lots also neutralized BA.2.75 and BA.2.75.2, with PsVNA50 titers of 22\u2013430 (GMT: 37 and 32, respectively). At least 10 hCoV-2IG lots demonstrated presence of antibodies against BQ.1, BQ.1.1, and XBB subvariants, but the neutralization titers were further reduced (GMT: 21\u201325; Figure 1A<\/a> and Supplemental Table 2<\/a>). Strong correlations were observed between PsVNA50 titers against WA-1\/2020 and BA.4\/BA.5, BA.2.75, and BA.2.75.2 (P<\/em> < 0.0001) for CP and hCoV-2IG (Figure 1B<\/a>). In contrast, weak insignificant correlations were observed between PsVNA50 titers against WA-1\/2020 and BQ.1, BQ.1.1, and XBB (Figure 1B<\/a>).<\/p>\n\n\n\n

Our study demonstrates that some hyperimmune COVID-IVIG lots manufactured in 2020 (2020-hCoV-2IG) neutralized several Omicron variants, similar to CP, from Omicron breakthrough infections in individuals with prior vaccination (2022-CP), at a level (PsVNA50 titer of >1:40) predicted to provide protection against severe COVID-19 (4<\/a>). Nevertheless, evolution of the variant landscape can increase resistance to antibodies elicited by prior SARS-CoV-2 infections and vaccination, especially against the newly emerged BQ.1, BQ.1.1, and XBB subvariants (5<\/a>). Therefore, high-titer hCoV-2IG batches could be generated from donors who have been boosted recently with Omicron-containing bivalent vaccine and\/or recovered from infection with Omicron following vaccination (hybrid immunity) (6<\/a>). While there are logistical challenges to hyperimmune globulin production (e.g., long lead time), hCoV-2IG have notable advantages over CP, including standardization of dose, pathogen reduction, and measurements of anti\u2013SARS-CoV-2 neutralizing titers prior to release. This could improve the hCoV-2IG therapeutic effectiveness against severe COVID-19 caused by circulating and emerging SARS-CoV-2 variants.<\/p>\n","protected":false},"excerpt":{"rendered":"

Lorenza Bellusci,\u00a0Hana Golding, and\u00a0Surender Khurana Journal of Clinical Investigation Published 2023 – More infoView PDF  Convalescent plasma (CP) and hyperimmune intravenous immunoglobulins (IVIGs) are routinely used to treat patients with COVID-19. […]<\/p>\n","protected":false},"author":2,"featured_media":8321,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[38,39,40,764,845,346,541,592,652],"tags":[],"class_list":["post-8313","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-ba-3-covid","category-ba-4-covid","category-ba-5-covid","category-convalescent-plasma","category-intravenous-immunoglobins","category-mutations","category-spike-protein","category-treatments","category-xbb"],"_links":{"self":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/posts\/8313","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=8313"}],"version-history":[{"count":0,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/posts\/8313\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/media\/8321"}],"wp:attachment":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=8313"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=8313"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=8313"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}