key: cord-0866163-oxiyjy31
authors: Tauzin, A.; Beaudoin-Bussieres, G.; Gong, S. Y.; Chatterjee, D.; Gendron-Lepage, G.; Bourassa, C.; Goyette, G.; Racine, N.; Khrifi, Z.; Turgeon, J.; Tremblay, C.; Martel-Laferriere, V.; Kaufmann, D. E.; Cloutier, M.; Bazin, R.; Duerr, R. E.; Dieude, M.; Hebert, M.-J.; Finzi, A.
title: Humoral immune responses against SARS-CoV-2 Spike variants after mRNA vaccination in solid organ transplant recipients
date: 2022-05-16
journal: nan
DOI: 10.1101/2022.05.13.22275056
sha: 7e6bc60c40a23e271fa6ca0ce060eab99d9f81e6
doc_id: 866163
cord_uid: oxiyjy31

While SARS-CoV-2 mRNA vaccination has been shown to be safe and effective in the general population, immunocompromised solid organ transplant recipients (SOTR) were reported to have impaired immune responses after one or two doses of vaccine. In this study, we examined humoral responses induced after the second and the third dose of mRNA vaccine in different SOTR (kidney, liver, lung and heart). Compared to a cohort of SARS-CoV-2 naive immunocompetent health care workers (HCW), the second dose induced weak humoral responses in SOTR, except for the liver recipients. The third dose boosted these responses but they did not reach the same level as in HCW. Interestingly, while the neutralizing activity against Delta and Omicron variants remained very low after the third dose, Fc-mediated effector functions in SOTR reached similar levels as in the HCW cohort. Whether these responses will suffice to protect SOTR from severe outcome remains to be determined.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent 42 of the coronavirus disease 2019 (COVID-19) responsible of the current pandemic. COVID-19 43 causes a plethora of symptoms with different degrees of severity (Sheikhi et al., 2020) . In solid 44 organ transplant recipients (SOTR), due to immunosuppressive treatments, SARS-CoV-2 45 infection leads to a high rate of severe COVID-19 (Danziger-Isakov et al., 2021; Pereira et al., 46 2020 ) and therefore vaccination is strongly recommended (AST, 2022; CST, 2022) . The 47

Pfizer/BioNTech BNT162b2 and Moderna mRNA-1273 mRNA vaccines have shown a 48 remarkable efficacy in the general population, particularly against severe outcomes (Baden et al., 49 2021; Polack et al., 2020) . However, in SOTR, immune responses induced by vaccination are 50 generally reduced (Kumar et al., 2011; Stucchi et al., 2018) and recent studies have shown that 51 SOTR have impaired humoral responses after two doses of the SARS-CoV-2 mRNA vaccine 52 (Caillard et al., 2021; Miele et al., 2021; Rabinowich et al., 2021; Rincon-Arevalo et al., 2021; 53 Stumpf et al., 2021) . 54

Moreover, SARS-CoV-2 is constantly evolving, and the Wuhan original strain has now 55 been replaced by several variants. Among current circulating strains, the Delta and Omicron 56 variants of concern (VOCs) have accumulated numerous mutations in their genome, and notably 57 in the Spike (S) glycoprotein (Kumar et al., 2022) . Because of the mutations, these VOCs are 58 transmitted more efficiently than the original Wuhan strain and less well controlled by vaccination 59 (Kumar et al., 2022; Lauring et al., 2022; Tseng et al., 2022) . However, the administration of a 60 third dose of mRNA vaccine (boost) leads to strong humoral responses and protects from severe 61 outcome caused by these VOCs in the general population (Ariën et al., 2022; Tauzin et al., 2022a; 62 RESULTS 67 We analyzed humoral immune responses in cohorts of 31 kidney, 11 liver, 14 lung and 8 68 heart organ transplant recipients after the second (median shown that this extended interval regimen leads to strong humoral and cellular responses after 80 the second dose, notably against VOCs (Chatterjee et al., 2022; Nayrac et al., 2021; Payne et al., 81 2021; Tauzin et al., 2022a) . This allowed us to compare humoral responses obtained in SOTR 82 versus humoral responses elicited by a long interval vaccination regimen. Basic demographic 83 characteristics of the cohorts, immunosuppressive treatments of the SOTR and detailed 84 vaccination time points are summarized in Table 1 and Figure 1A . 85 86

We first measured anti-receptor-binding domain (RBD) IgG levels induced after the 88 second and the third doses of the mRNA vaccine using a previously reported ELISA assay (Anand 89 et al., 2021; Beaudoin-Bussières et al., 2020; Prévost et al., 2020; Tauzin et al., 2021) . After the 90 second dose, all HCW presented high levels of RBD-specific IgG ( Figure 1B ). In contrast, in all 91 groups of SOTR, the levels of anti-RBD antibodies (Abs) were, with the exception of liver 92 recipients, significantly lower than in HCW. We also noted that in every SOTR group, some donors 93 did not have anti-RBD IgG after the second dose of mRNA vaccine. Among SOTR, liver recipients 94 had higher Ab levels than kidney, lung and heart recipients, in line with a generally lower 95 immunosuppression regimen. For HCW, the third dose of the mRNA vaccine led to the same level 96 of Abs as after the second dose, as recently described (Tauzin et al., 2022a) . For SOTR, we 97 observed a significant increase in the level of anti-RBD IgG in lung recipients and a trend for 98 kidney and heart recipients. No increase in anti-RBD IgG level was observed for liver recipients. 99

Of note, in all SOTR groups, anti-RBD levels remained significantly lower than in the HCW cohort 100 even after the third dose, but most donors who did not have anti-RBD IgG after the second dose 101 developed antibodies after the third dose, suggesting the initiation of an antibody response by 102 repeated antigen exposure. 103 104

We next evaluated the recognition of the SARS-CoV-2 full-length S after vaccination in 106 SOTR and HCW by flow cytometry (Figure 2A ). After the second vaccine dose, no significant 107 differences were observed in the recognition of the D614G S by plasma from kidney and liver 108 recipients and HCW. In contrast, lung and heart recipients recognized the D614G S less 109 efficiently. The third dose increased the D614G S recognition for HCW, and we noted a slight 110 increase for lung and heart recipients, for whom the recognition was very weak after the second 111 dose. For kidney and liver recipients, the third dose did not improve the D614G S recognition 112 recognition of these VOCs S after mRNA vaccination in SOTR ( Figure 2B -C). We did not see 118 significant differences in the level of recognition of Delta and Omicron S between liver recipients 119 and HCW after the second dose. The third dose led to a slight increase of the recognition of the 120 VOCs S except for liver recipients, however it remained significantly lower than in HCW. When 121 we compared S recognition between the SARS-CoV-2 variants ( Figure S1 ), we observed that in 122 HCW, because of strong humoral responses induced by the extended interval, no major 123 differences in recognition were observed between D614G and VOCs S after the second and third 124 doses of mRNA vaccine ( Figure S1A ). For SOTR, VOCs S were significantly less recognized than 125 the D614G S, suggesting that vaccination in SOTR did not improve the breadth of S recognition, 126 as observed in HCW (Figure S1B-E). 127

We also evaluated the recognition of the human HKU1 Betacoronavirus S glycoprotein 128 ( Figure 2D ). HKU1 is an endemic coronavirus that causes common colds and is highly prevalent 129 in the population (Chan et al., 2009; Rees et al., 2021) . No significant differences between HCW 130 and SOTR were observed after the second and the third doses of the vaccine, indicating that 131 transplantation and associated immunosuppression regimens did not affect the level of circulating 132

Abs elicited before vaccination. 133 134

We evaluated functional activities of vaccine-elicited Abs after the second and third doses 136 of mRNA vaccine (Figure 3 ). We measured Fc-mediated effector functions using a well-described 137 antibody-dependent cellular cytotoxicity (ADCC) assay (Anand et al., 2021; Beaudoin-Bussières 138 et al., 2020 Ullah et al., 2021) . Plasma from HCW presented robust ADCC activity after 139 the second dose that was restored to the same level by the third dose ( Figure 3A ). The second 140 dose elicited ADCC-mediating Abs in liver and heart recipients that reached similar levels of 141 activity as in HCW. This is in contrast with significant lower ADCC activity elicited after the second 142 dose in kidney and lung recipients. The boost led to a significant increase in ADCC activity in 143 these donors. Importantly, the third dose elicited ADCC activity in all SOTR similar to the one 144 observed in HCW. 145

We also measured the neutralizing activity of the vaccine-induced Abs, against 146 pseudoviruses carrying SARS-CoV-2 S ( Figure 3B-D) . When assessing the neutralizing activity 147 against the D614G S, we observed that the second dose elicited Abs with neutralizing activity in 148 liver recipients ( Figure 3B ). In other SOTR, very low levels of neutralizing Abs were detected, 149 especially in lung recipients. As observed for ADCC activity, the boost increased the neutralization 150 activity in kidney and lung recipients. However, even after the third dose, SOTR did not reach the 151 same levels of neutralizing Abs as in HCW. 152

We also measured the neutralizing activity against pseudoviruses carrying the Delta and 153

Omicron Spikes ( Figure 3C -D). In HCW, the second dose of mRNA vaccine administered with a 154 16-weeks interval, led to high levels of Abs able to neutralize these variants, as previously 155 described (Chatterjee et al., 2022; Payne et al., 2021; Tauzin et al., 2022a) . In contrast, SOTR 156 elicited very low levels of neutralizing Abs against Delta and Omicron variants after the second 157 dose and, although the boost led to a slight increase of the neutralization activity, this remained 158 significantly lower than in HCW. 159

When comparing the neutralizing activity between the SARS-CoV-2 variants ( Figure S2 We also used a surrogate assay for antibody maturation by measuring the avidity for the 167 RBD of vaccine-elicited Abs, using a previously described assay (Björkman et al., 1999; Fialová 168 et al., 2017; Tauzin et al., 2022a Tauzin et al., , 2022b Tauzin et al., , 2022c . Briefly, plasma samples were tested in parallel 169 by ELISA with washing steps having or not having a chaotropic agent (8M urea), measuring 170 respectively the level of IgG with high avidity for the RBD and the level of total anti-RBD IgG. The 171 RBD-avidity index corresponds to the proportion of high avidity IgG among the total anti-RBD IgG 172 (Figures 4) , and provides an overall idea of antibody maturation (Björkman et al., 1999; Fialová 173 et al., 2017; Tauzin et al., 2022a Tauzin et al., , 2022b Tauzin et al., , 2022c . 174

In HCW, the second dose of the mRNA vaccine elicited IgG with high avidity, that was not 176 further improved by the boost (Figure 4 ), as recently described (Tauzin et al., 2022a) . In contrast, 177 in SOTR who developed Abs able to recognize the RBD, the avidity was significantly lower than 178 in HCW ( Figure 1B and 4) . The third dose of mRNA vaccine increased RBD avidity in SOTR but, 179 with the exception of liver recipients, remained significantly lower than in HCW. 180

We evaluated the network of pairwise correlations among all studied immune variables on 183 the HCW and the different SOTR groups ( Figure 5 ). For HCW, we observed that after the second 184 dose all immune variables tested were involved in a dense network of positive correlations. After 185 the boost, we did not observe major differences in the network of correlations, suggesting that the 186 third dose did not induce qualitatively different humoral responses in HCW. For lung and heart 187 recipients, who received the strongest immunosuppressive regimens, we observed that all 188 immune variables were very weakly interconnected after the second dose and the third dose did 189 not strongly increase the network. Immune variables were slightly more interconnected for kidney 190 recipients, which aligns with their lower immunosuppressive regimen compared to heart and lung 191 recipients. For liver recipients, the network of correlation was less dense than in HCW after the 192 second dose as observed for the other groups of SOTR. Interestingly, in this less 193 immunosuppressed group of SOTR, the third dose of the mRNA vaccine induced a dense network 194 of correlations, which was in a comparable range as in HCW. 195 All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. While a large part of the world population is vaccinated with two or three doses of CoV-2 vaccines, some population groups remain vulnerable to SARS-CoV-2 infection and most 198 importantly to severe outcomes. Here we show that SOTR, known to respond less efficiently to 199 vaccination due to their chronic immunosuppressive regimen (Kumar et al., 2011; Stucchi et al., 200 2018) , elicited poor humoral responses after the second dose of SARS-CoV-2 mRNA vaccine, 201 compared to HCW. The boost induced an increase of these responses, but they did not reach the 202 same level as observed in HCW. 203

An important concern about the evolving pandemic is the frequent apparition of variants. 205

It was previously shown that the 3-4 weeks standard interval of vaccination leads to weak 206 neutralizing Abs against several VOCs in the general population (Chatterjee et al., 2022; Payne 207 et al., 2021; Tauzin et al., 2022a Tauzin et al., , 2022c . However, administering a boost strongly enhances the 208 breadth of neutralization activity against these variants (Nemet et al., 2022; Schmidt et al., 2022; 209 Tauzin et al., 2022a) . In SOTR, we did not observe a significant increase in the breadth of 210 recognition and neutralization of these variants, suggesting an inability in Abs maturation in most 211 of these individuals. This is supported by the poor anti-RBD avidity detected in these individuals, 212 likely reflecting poor B cells maturation compared to HCW. 213 214 Interestingly, we observed that SOTR elicited Abs with ADCC activity comparable to HCW 215 after the third dose of the mRNA vaccine. There is increasing evidence showing that Fc-mediated 216 effector functions play an important role in the protection against severe outcomes of SARS-CoV-217 2 (Anand et al., 2021; Richardson et al., 2022; Tauzin et al., 2021) . However, whether this will 218 suffice to protect SOTR from severe outcomes caused by SARS-CoV-2 remains unknown. 219 220 All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 16, 2022.

We also noted some differences in humoral responses, depending on the transplanted 221 organ. Notably, we observed that liver recipients had better humoral responses than other SOTR 222 groups. These differences are probably due to the lower immunosuppressive regimens in liver 223 recipients than in other SOTR groups. Further work is needed to understand the correlation 224 between specific immunosuppressive regimens and vaccination outcome, taking into account the 225 dose and type of immunosuppressive agents, and response to SARS-CoV-2 vaccines. This also 226 highlights the importance of evaluating the different SOTR groups independently regarding the 227 decisions on the follow-up of vaccinations that needs to be adapted to each SOTR group. 

The authors declare no competing interests. 264 265 All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 16, 2022. ; https://doi.org/10. 1101 represented as white symbols, and limits of detection are plotted. Error bars indicate means ± 289 SEM. (* p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001; ns, non-significant). Indirect ELISA and stringent ELISA were performed by incubating plasma samples from SOTR 310

and HCW with recombinant SARS-CoV-2 RBD protein. Anti-RBD Ab binding was detected using 311 HRP-conjugated anti-human IgG. The RBD avidity index corresponded to the RLU value obtained 312 All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 

All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 

The study was conducted in 20 SARS-CoV-2 naïve vaccinated HCW (8 males and 12 females; (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. FreeStyle 293F cells (Invitrogen) were grown in FreeStyle 293F medium (Invitrogen) to a density 404 of 1 x 10 6 cells/mL at 37°C with 8 % CO2 with regular agitation (150 rpm). Cells were transfected 405 All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 16, 2022. ; https://doi.org/10.1101/2022.05.13.22275056 doi: medRxiv preprint with a plasmid coding for SARS-CoV-2 S RBD (Beaudoin-Bussières et al., 2020) using 406

ExpiFectamine 293 transfection reagent, as directed by the manufacturer (Invitrogen). One week 407 later, cells were pelleted and discarded. Supernatants were filtered using a 0.22 µm filter (Thermo 408

Fisher Scientific). The recombinant RBD proteins were purified by nickel affinity columns, as 409 directed by the manufacturer (Invitrogen). The RBD preparations were dialyzed against 410 phosphate-buffered saline (PBS) and stored in aliquots at -80°C until further use. To assess 411 purity, recombinant proteins were loaded on SDS-PAGE gels and stained with Coomassie Blue. 412 413

The SARS-CoV-2 RBD ELISA assay used was previously described (Beaudoin-Bussières et al., 415 2020; Prévost et al., 2020) . Briefly, recombinant SARS-CoV-2 S RBD proteins (2.5 μg/ml) were 416 prepared in PBS and were adsorbed to plates (MaxiSorp Nunc) overnight at 4°C. Coated wells 417 were subsequently blocked with blocking buffer (Tris-buffered saline [TBS] containing 0.1% 418 Tween20 and 2% BSA) for 1h at room temperature. Wells were then washed four times with 419 washing buffer (Tris-buffered saline [TBS] containing 0.1% Tween20). CR3022 mAb (50 ng/ml) 420 or a 1/250 dilution of plasma were prepared in a diluted solution of blocking buffer (0.1 % BSA) 421 and incubated with the RBD-coated wells for 90 minutes at room temperature. Plates were 422 washed four times with washing buffer followed by incubation with secondary Abs (diluted in a 423 solution of blocking buffer (0.4% BSA)) for 1h at room temperature, followed by four washes. To 424 calculate the RBD-avidity index, we performed in parallel a stringent ELISA, where the plates 425 were washed with a chaotropic agent, 8M of urea, added of the washing buffer. This assay was 426 previously described (Tauzin et al., 2022b) . HRP enzyme activity was determined after the 427 addition of a 1:1 mix of Western Lightning oxidizing and luminol reagents (Perkin Elmer Life 428

Technologies). Signal obtained with BSA was subtracted for each plasma and was then 430 normalized to the signal obtained with CR3022 present in each plate. The seropositivity threshold 431 All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 16, 2022. ; https://doi.org/10.1101 https://doi.org/10. /2022 was established using the following formula: mean of pre-pandemic SARS-CoV-2 negative 432 plasma + (3 standard deviation of the mean of pre-pandemic SARS-CoV-2 negative plasma). (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 16, 2022. ; https://doi.org/10.1101 https://doi.org/10. /2022 Plasma (1/500 dilution) were added to the appropriate wells. The plates were subsequently 458 centrifuged for 1 min at 300g, and incubated at 37°C, 5% CO2 for 5 hours before being fixed in a 459 2% PBS-formaldehyde solution. ADCC activity was calculated using the formula: [(% of GFP+ 460 cells in Targets (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 16, 2022. ; https://doi.org/10.1101/2022.05.13.22275056 doi: medRxiv preprint

Symbols represent biologically independent samples from SOTR and HCW. Lines connect data 486 from the same donor. Statistics were analyzed using GraphPad Prism version 8.0.1 (GraphPad, 487 San Diego, CA). Every dataset was tested for statistical normality and this information was used 488 to apply the appropriate (parametric or nonparametric) statistical test. Differences in responses 489 for the same donor after the second and third dose of mRNA vaccine were performed using Mann-490

Whitney tests. Differences in responses between HCW and SOTR at D2 or D3 were measured 491 by Kruskal-Wallis tests. P values < 0.05 were considered significant; significance values are 492 indicated as * p < 0.05, * * p < 0.01, * * * p < 0.001, * * * * p < 0.0001. Spearman's R correlation 493 coefficient was applied for correlations. Statistical tests were two-sided and p < 0.05 was 494 considered significant. 495 496

Edge bundling graphs were generated in undirected mode in R and RStudio using ggraph, igraph, 498 tidyverse, and RColorBrewer packages (R Core Team, 2014) . Edges are only shown if p < 0.05, 499 and nodes are sized according to the connecting edges' r values. Nodes are color-coded 500 according to groups of variables. 501

Supplemental information can be found online at … 504 All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 16, 2022. ; https://doi.org/10.1101 https://doi.org/10. /2022 Anand, S.P., Prévost, J., Richard, J., Perreault, J., Tremblay, T., Drouin, M., Fournier, 506 Lewin, A., Bazin, R., and Finzi, A. (2020). High-throughput detection of antibodies targeting the 507 SARS-CoV-2 Spike in longitudinal convalescent plasma samples (Microbiology). 508

Anand, S.P., Prévost, J., Nayrac, M., Beaudoin-Bussières, G., Benlarbi, M., Gasser, R., Brassard, 509 N., Laumaea, A., Gong, S.Y., Bourassa, C., et al. (2021) . Beaudoin-Bussières, G., Laumaea, A., Anand, S.P., Prévost, J., Gasser, R., Goyette, G., 523 Medjahed, H., Perreault, J., Tremblay, T., Lewin, A., et al. (2020) Beaudoin-Bussières, G., Richard, J., Prévost, J., Goyette, G., and Finzi, A. (2021) . A new flow 527 cytometry assay to measure antibody-dependent cellular cytotoxicity against SARS-CoV-2 Spike-528 expressing cells. STAR Protoc. 2, 100851. https://doi.org/10. 1016 /j.xpro.2021 .100851. 529 Björkman, C., Näslund, K., Stenlund, S., Maley, S.W., Buxton, D., and Uggla, A. (1999 . An IgG 530

Avidity ELISA to Discriminate between Recent and Chronic Neospora Caninum Infection. J. Vet. 531 Diagn. Invest. 11, 41-44. https://doi.org/10.1177 /104063879901100106. 532 Caillard, S., Chavarot, N., Bertrand, D., Kamar, N., Thaunat, O., Moal, V., Masset, C., Hazzan, 533 M., Gatault, P., Sicard, A., et al. (2021 Chatterjee, D., Tauzin, A., Marchitto, L., Gong, S.Y., Boutin, M., Bourassa, C., Bussières, G., Bo, Y., Ding, S., Laumaea, A., et al. (2022) . SARS-CoV-2 Omicron Spike 541 recognition by plasma from individuals receiving BNT162b2 mRNA vaccination with a 16-week 542 interval between doses. Cell Rep. 110429. https://doi.org/10.1016 Rep. 110429. https://doi.org/10. /j.celrep.2022 All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 16, 2022. ; https://doi.org/10.1101 .05.13.22275056 doi: medRxiv preprint CST (2022 Gong, S.Y., Chatterjee, D., Richard, J., Prévost, J., Tauzin, A., Gasser, R., Bo, Y., Vézina, D., 554 Goyette, G., Gendron-Lepage, G., et al. (2021) . antibodies against SARS-CoV-2 emerging variants of concern. Cell Rep. Miele, M., Busà, R., Russelli, G., Sorrentino, M.C., Di Bella, M., Timoneri, F., Mularoni, A., 582

Panarello, G., Vitulo, P., Conaldi, P. G., et al. (2021) . Impaired anti-SARS-CoV-2 Humoral and 583 Cellular Immune Response induced by Pfizer-BioNTech BNT162b2 mRNA Vaccine in Solid 584 All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 

Temporal associations of B and T cell immunity 588 with robust vaccine responsiveness in a 16-week interval BNT162b2 regimen

Third BNT162b2 Vaccination Neutralization of 592 SARS-CoV-2 Omicron Infection

Immunogenicity of standard and extended 596 dosing intervals of BNT162b2 mRNA vaccine

COVID-19 in solid organ transplant 600 recipients: Initial report from the US epicenter

Considerable escape of SARS-CoV

Omicron to antibody neutralization

Safety and Efficacy of the BNT162b2 mRNA 607

Covid-19 Vaccine

Cross-Sectional Evaluation of Humoral 610 Responses against SARS-CoV-2 Spike

R: A language and environment for statistical computing. R Foundation for 613 Statistical Computing

Low immunogenicity to SARS-CoV-2 vaccination 616 among liver transplant recipients

Estimating the duration of 619 seropositivity of human seasonal coronaviruses using seroprevalence studies

SARS-CoV-2 Beta and Delta 623 variants trigger Fc effector function with increased cross-reactivity

Impaired humoral immunity to SARS-627

CoV-2 BNT162b2 vaccine in kidney transplant recipients and dialysis patients

A Review on Novel Coronavirus (Covid-19): 633 Symptoms, Transmission and Diagnosis Tests

Vaccine Recommendations for 636 Solid-Organ Transplant Recipients and Donors

Humoral and cellular immunity to SARS-640

CoV-2 vaccination in renal transplant versus dialysis patients: A prospective, multicenter 641 observational study using mRNA-1273 or BNT162b2 mRNA vaccine

BNT162b2 elicits Fc-mediated antibody effector functions and T cell responses

A boost with SARS-CoV-2

BNT162b2 mRNA vaccine elicits strong humoral responses independently of the interval between 650 the first two doses

Following SARS-CoV-2 Infection

Strong humoral immune responses 656 against SARS-CoV-2 Spike after BNT162b2 mRNA vaccination with a 16-week interval between 657 doses

Effectiveness of mRNA-1273 against SARS-CoV-2 660

Omicron and Delta variants

Live imaging of SARS-CoV-2 infection in mice 663

After the third dose