We also thank the Ministry of Public Health, Chulabhorn Royal Academy, and Zullig pharma for providing the vaccines for this study. Footnotes Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.ijid.2022.07.038. Appendix.?Supplementary materials Click here to view.(1.4M, docx)Image, application 1. immunoglobulin (Ig) levels, anti-RBD IgG, and focus reduction neutralization test against Omicron BA.1 and BA.2 variants and T cell response peaked at 14-28 days after booster vaccination. Both the full and half dose of mRNA-1273 induced the highest response, followed by BNT162b2 and AZD1222. At 90 days, the persistence of immunogenicity was observed among all mRNA-boosted individuals. Adverse events were acceptable for all vaccines. Conclusion A heterologous mRNA booster provided a significantly superior boost of binding and NAbs levels against the Omicron variant compared with a homologous booster in individuals with AZD1222-primed vaccinations. 0.01, ***, 0.001. BAU?=?binding antibody units; CI?=?confidence interval; GMT?=?geometric mean titer; IgG?=?immunoglobulin G; mRNA?=?messenger RNA; RBD?=?receptor-binding domain. Surrogate virus neutralization specific Delta and Omicron variants A subset of the sample was tested for sVNT in the prebooster stage. At 28 days after boosters, the median percentage inhibition (% inhibition) to the Delta variant was significantly elevated to 93.5% in AZD1222, 96.9% in AR-9281 BNT162b2, 97.0% in mRNA-1273, and 97.9% in half-dose mRNA-1273 (Figure?3 a). Whereas, a lower % inhibition was observed against Omicron variants with 15.0%, 67.1%, 64.6%, and 65.7% in groups AZD1222, BNT162b2, mRNA-1273, and half-dose mRNA-1273, respectively (Figure?3b). These findings suggested that heterologous-boosted individuals achieved a higher level of NAbs against the Omicron variant than homologous-boosted individuals. On day 90 after vaccination, the median % inhibition to Delta variant slightly decreased to 78.0% in the AZD1222-boosted group, while the other groups remained 97% inhibition. In contrast to the Omicron variant, the median % inhibition was reduced to 9.0% for AZD1222, 33.2% for BNT162b2, 35.5% for mRNA-1273, and 38.7% for half-dose AR-9281 mRNA-1273, respectively. Correspondingly, the neutralizing activity against the Omicron variant was significantly lower than that against the Delta variant (Figure?3c). The heterologous AZD1222/mRNA prime-boosted achieved higher detectable neutralization activities against Omicron than the homologous booster at both the day 28 and day 90 time point (Supplementary Table 3). Open in a separate window Figure 3 Neutralizing activities of Delta and Omicron variants compared between preboost and postboost using a surrogate virus neutralization test A subset of samples was randomly selected to test for sVNT, including sera collected at baseline and sera collected 28 days and 90 days after boost (n?=?30/group). (A) Neutralizing activities against the SARS-CoV-2 Delta variant and (B) neutralizing activities against the SARS-CoV-2 Omicron variant (BA.1) were shown as % inhibition. (C) Comparison of the neutralizing activity between the Delta and Omicron variants after booster vaccination. Median values with IQR are denoted as horizontal bars. Horizontal bars indicate the median. Dotted lines designate cutoff Rabbit polyclonal to XIAP.The baculovirus protein p35 inhibits virally induced apoptosis of invertebrate and mammaliancells and may function to impair the clearing of virally infected cells by the immune system of thehost. This is accomplished at least in part by its ability to block both TNF- and FAS-mediatedapoptosis through the inhibition of the ICE family of serine proteases. Two mammalian homologsof baculovirus p35, referred to as inhibitor of apoptosis protein (IAP) 1 and 2, share an aminoterminal baculovirus IAP repeat (BIR) motif and a carboxy-terminal RING finger. Although thec-IAPs do not directly associate with the TNF receptor (TNF-R), they efficiently blockTNF-mediated apoptosis through their interaction with the downstream TNF-R effectors, TRAF1and TRAF2. Additional IAP family members include XIAP and survivin. XIAP inhibits activatedcaspase-3, leading to the resistance of FAS-mediated apoptosis. Survivin (also designated TIAP) isexpressed during the G2/M phase of the cell cycle and associates with microtublules of the mitoticspindle. In-creased caspase-3 activity is detected when a disruption of survivin-microtubuleinteractions occurs values (30%). IQR?=?interquartile range; mRNA?=?messenger RNA; sVNT?=?surrogate virus neutralization test. Focus reduction neutralization test against the BA.1 and BA.2 variants Most participants showed undetectable NAbs at baseline. Then, 28 days after receiving AR-9281 a booster, the GMTs of NAbs against BA.1 and BA.2 were significantly increased compared with baseline (Figure?4 a and b). Consistent with those binding antibodies, the GMR of NAbs against BA.1 ranged from 5.56 (95% CI: 2.70-11.43) in the BNT162b2 group to 18.03 (95% CI: 8.89-36.56) in the mRNA-1273 group. While the GMR of NAbs against BA.2 ranged from 5.43 (95% CI: 2.64-11.17) in the BNT162b2 group to 7.11 (95% CI: 3.45-14.62) in the mRNA-1273 groups (Supplementary Table 1). Then, 90 days after vaccination, a significant decrease in NAbs levels was observed, and the percentage of reduction ranged between 30-75% depending on booster vaccines (Supplementary Table 2). The NAb titers of BA.1 were comparable with BA.2 (Figure?4c and d), and higher activity was observed to neutralize the Omicron variant in the heterologous mRNA-boosted than in the homologous AZD1222-boosted individuals. Open in a separate window Figure 4 Neutralizing antibody titers against Omicron BA.1 and BA.2 before and after booster vaccination Neutralization of SARS-CoV-2 Omicron BA.1 and BA.2 was measured using FRNT50. (A) Neutralization against the BA.1 Omicron variant and (B) neutralization against the BA.2 Omicron variant. (C) Comparison of AR-9281 NAb titers against BA.1 and BA.2 28 days after the booster dose. (D) Comparison of NAb titers against BA.1 and BA.2 90 days after the booster dose. Each data point represents an individual who received a booster vaccine, including the viral vector vaccine, AZD1222 (purple),.