key: cord-1000985-mtnazqv7 authors: Focosi, Daniele; Tuccori, Marco; Baj, Andreina; Maggi, Fabrizio title: SARS-CoV-2 Variants: A Synopsis of In Vitro Efficacy Data of Convalescent Plasma, Currently Marketed Vaccines, and Monoclonal Antibodies date: 2021-06-23 journal: Viruses DOI: 10.3390/v13071211 sha: f89d61a23838e1615efc95b315eb93d59179088c doc_id: 1000985 cord_uid: mtnazqv7 We summarize here in vitro evidences of efficacy for convalescent plasma, currently approved vaccines and monoclonal antibodies against SARS-CoV-2 variants of concern (VOC: B.1.1.7, B.1.351, P.1, and B.1.617.2), variants of interest (VOI: B.1.427/B.1.429, P.2, B.1.525, P.3, B.1.526, and B.1.671.1), and other strains (B.1.1.298 and B.1.258delta). While waiting from real world clinical efficacy, these data provide guidance for the treating physician. The ongoing SARS-CoV-2 pandemic has entered a new dimension thanks to availability of different vaccines and neutralizing antibody-based therapeutics (from convalescent plasma to monoclonal antibodies). Nevertheless, emerging of SARS-CoV-2 variants of concern (VOC) and variants of interest (VOI) [1] has diversified the landscape, jeopardizing the efforts to contain it. Media-informed patients are questioning physicians about the relative efficacy of different vaccines and treatments against different variants. The majority of registration trials for currently approved monoclonal antibodies and vaccines were run either before the variants emerged, or enrolled patients in countries where such variants were not circulating at that time. While waiting for post-marketing clinical efficacy data (i.e., protection from symptomatic COVID19), many investigators have tested the neutralizing efficacy of monoclonal antibodies, convalescent plasma from previous waves or vaccinee sera in vitro to accelerate availability of surrogate endpoints. Different nonviral (e.g., synthetic RBD) and viral constructs (ranging from isogenic strain, pseudovirus harboring the full mutation set, or authentic variant virus) have been employed to test the efficacy of therapeutics in neutralization assays [2] . On 15 May 2021, we mined PubMed and preprint servers (medrXiv and biorXiv) for in vitro data detailing the efficacy of different anti-Spike vaccines and monoclonal antibodies against different variants compared to wild-type SARS-CoV-2. Table 1 reports the result of our search and analysis. We decided to simplify interpretation of results using a semiquantitative scale according to the number of fold decrease in neutralization efficacy. We also tabulated for each variant the estimated reinfection rates, and the proven reinfection cases (strains from each episode sequenced). Each variant was reported using both the official (PANGOLIN and NextStrain) and the local (VUI/VOC/VOI) naming systems, and colloquial terms (e.g., "UK variant") in order to provide comprehensive association. The main, alarming finding is the lack of efficacy of single-agent bamlanivimab against most E484K-carrying variants. Accordingly, the FDA has recently withdrawn its emergency use authorization as a single agent, leaving the authorization only for usage vaccinees against every variant tested: 5.2-fold against B.1.1.7, 6.5-fold against B.1.351, 4.3-fold against P.1, and 3.4-fold against original SARS-CoV-2 [17] . Similarly, a single dose of either BNT162b2 or AZD1222 vaccines in convalescents raised the titre of antibodies against the SARS-CoV-2 vaccine strain (B.1) and three major VOCs (B.1.1.7, B.1351 and P.1). A single dose to convalescents is nowadays a well-accepted approach that saves money and side effects [18] . Apart from efficacy, many topics remain under investigation for vaccines: • vaccine-elicited T-cell immunity: while neutralizing antibodies are just one arm of the adaptive immune response to vaccines, very few data are available for protection from T-cell immunity, which would be especially relevant in the ones who do not mount antibody responses. Gallagher postponing second doses has been widely implemented in order to optimize vaccine delivery under manufacturing bottlenecks. In nonconvalescent elderlies higher than age 80 who received the second dose of BNT162b2 after 12 weeks instead of 3, the peak antibody response was 3.5-fold higher, but cellular immune responses were 3.6-fold lower [23] . • heterologous boosting: heterologous immunization strategy combining inactivated and mRNA vaccines can generate robust vaccine responses and therefore provide a rational and effective vaccination regimen [24] . ChAdOx/BNT162b2 booster vaccination was largely comparable to homologous BNT162b2/BNT162b2 vaccination and overall well-tolerated. No major differences were observed in the frequency or severity of local reactions after either of the vaccinations. In contrast, notable differences between the regimens were observed for systemic reactions, which were most frequent after prime immunization with ChAdOx (86%) and less frequent after homologous BNT162b2/BNT162b2 (65%), or heterologous ChAdOx/BNT162b2 boosters (48%) [25] . Neutralizing activity against the prevalent strain B.1.1.7 was 3.9-fold higher than in individuals receiving homologous BNT162b2 vaccination, only 2-fold reduced for variant of concern B.1.351, and similar for variant B.1.617 [26] . Whilst both ChAdOx and BNT162b2 boosted prime-induced immunity, BNT induced significantly higher frequencies of Spike-specific CD4 and CD8 T cells and, in particular, high titers of neutralizing antibodies against the B.1.1.7, B.1.351 and the P.1 VOCs [27] . [28] [29] [30] [31] [32] [33] [34] [35] ↓↓↓ [29, 31, 33, 34, [36] [37] [38] [39] [40] [41] ↓↓↓ [42] = [43] ↓ [44] [45] [46] ↓↓ [41] = [47] ↓↓↓ [48] (hamsters) ↓↓ [49] ? ? ↓↓ [50, 51] ? ↓ [52] ? hyperimmune serum (polyvalent immunoglobulins) = [53] ↓↓↓ [53] ↓↓↓ [53] ? [29, 37, 62, 63] = [29, 63] ↓↓↓ [37, 42, 62] ↓↓↓ [44] [45] [46] 64] ↓↓↓ [63] ↓↓↓ [49, 65] ? ? ↓↓↓ [50, 51] ? ↓↓ [35, 42, 75, 76, 85] ↓↓↓ [44] [45] [46] 86, 87] COVID19 88% [84] ↓ [63] =/↓↓ [49, 75] RBD [78] ? ↓ [88] ↓↓ [50, 51] ? ? = [75] Moderna mRNA-1273 ↓ [15, 29, 38, 74, 75, 89] ↓ NHP COVID19 [90] = [29, 30, 89] ↓ [74, 75, 91, 92] =/↓ [42, 75] ↓↓ [44, 87] VOC: variants of concern; VOI: variant of interest; NHP: nonhuman primates. = and arrows indicate fold-reductions in neutralizing activity compared to wild-type D614G strain. =: no reduction; ↓: 1-3 fold reduction; ↓↓: 3-5 fold reduction; ↓↓↓: > 5 fold reduction; ?: data not available). COVID19 refers to vaccine efficacy against symptomatic diseases in humans (if not otherwise indicated) or in animal models (specified). RBD: ACE2-RBD competition assay. While the in vitro findings summarized here wait for confirmatory clinical evidences, in the meanwhile they could orient therapeutic and preventive strategies. Funding: This research received no external funding. The data presented in this study are openly available in PubMed. We declare we have no conflict of interest related to this manuscript. 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