RESUMO
BACKGROUND: We studied whether comorbid conditions affect strength and duration of immune responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA vaccination in a US-based, adult population. METHODS: Sera (before and after BNT162b2 vaccination) were tested serially up to 12 months after 2 doses of vaccine for SARS-CoV-2-anti-Spike neutralizing capacity by pseudotyping assay in 124 individuals; neutralizing titers were correlated to clinical variables with multivariate regression. Postbooster (third dose) effect was measured at 1 and 3 months in 72 and 88 subjects, respectively. RESULTS: After completion of primary vaccine series, neutralizing antibody half maximal inhibitory concentration (IC50) values were high at 1 month (14-fold increase from prevaccination), declined at 6 months (3.3-fold increase), and increased at 1 month postbooster (41.5-fold increase). Three months postbooster, IC50 decreased in coronavirus disease (COVID)-naïve individuals (18-fold increase) and increased in prior COVID 2019 (COVID-19+) individuals (132-fold increase). Age >65 years (ß = -0.94, P = .001) and malignancy (ß = -0.88, P = .002) reduced strength of response at 1 month. Both neutralization strength and durability at 6 months, respectively, were negatively affected by end-stage renal disease ([ß = -1.10, P = .004]; [ß = -0.66, P = .014]), diabetes mellitus ([ß = -0.57, P = .032]; [ß = -0.44, P = .028]), and systemic steroid use ([ß = -0.066, P = .032]; [ß = -0.55, P = .037]). Postbooster IC50 was robust against WA-1 and B.1.617.2. Postbooster neutralization increased with prior COVID-19 (ß = 2.9, P < .0001), and malignancy reduced neutralization response (ß = -0.68, P = .03), regardless of infection status. CONCLUSIONS: Multiple clinical factors affect the strength and duration of neutralization response after primary series vaccination, but not the postbooster dose strength. Malignancy was associated with lower booster-dose response regardless of prior COVID infection, suggesting a need for clinically guided vaccine regimens.
Assuntos
COVID-19 , Adulto , Humanos , Idoso , COVID-19/epidemiologia , COVID-19/prevenção & controle , SARS-CoV-2 , Vacina BNT162 , Vacinas contra COVID-19 , Vacinação , Anticorpos Neutralizantes , RNA Mensageiro , Anticorpos AntiviraisRESUMO
Background: We studied whether comorbid conditions impact strength and duration of immune responses after SARS-CoV-2 mRNA vaccination in a US-based, adult population. Methods: Sera (pre-and-post-BNT162b2 vaccination) were tested serially up to 12 months after two doses of vaccine for SARS-CoV-2-anti-Spike neutralizing capacity by pseudotyping assay in 124 individuals; neutralizing titers were correlated to clinical variables with multivariate regression. Post-booster (third dose) effect was measured at 1 and 3 months in 72 and 88 subjects respectively. Results: After completion of primary vaccine series, neutralizing antibody IC50 values were high at one month (14-fold increase from pre-vaccination), declined at six months (3.3-fold increase), and increased at one month post-booster (41.5-fold increase). Three months post-booster, IC50 decreased in COVID-naïve individuals (18-fold increase) and increased in prior COVID-19+ individuals (132-fold increase). Age >65 years (ß=-0.94, p=0.001) and malignancy (ß=-0.88, p=0.002) reduced strength of response at 1 month. Both strength and durability of response at 6 months, respectively, were negatively impacted by end-stage renal disease [(ß=-1.10, p=0.004); (ß=-0.66, p=0.014)], diabetes mellitus [(ß=-0.57, p=0.032); (ß=-0.44, p=0.028)], and systemic steroid use [(ß=-0.066, p=0.032); (ß=-0.55, p=0.037)]. Post-booster IC50 was robust against WA-1 and B.1.617.2, but the immune response decreased with malignancy (ß =-0.68, p=0.03) and increased with prior COVID-19 (p-value < 0.0001). Conclusion: Multiple clinical factors impact the strength and duration of neutralization response post-primary series vaccination, but not the post-booster dose strength. Prior COVID-19 infection enhances the booster-dose response except in individuals with malignancy, suggesting a need for clinically guiding vaccine dosing regimens. Summary: Multiple clinical factors impact the strength and duration of neutralization response post-primary series vaccination. All subjects, irrespective of prior COVID infection, benefited from a third dose. Malignancy decreased response following third dose, suggesting the importance of clinically guided vaccine regimens.
RESUMO
Imprinted small nucleolar RNAs (snoRNAs) are only found in eutherian genomes and closely related to brain functions. A complex human neurological disease, Prader-Willi syndrome (PWS), is primarily attributed to the deletion of imprinted snoRNAs in chromosome 15q11-q13. Here we investigated the snoRNA repertoires in the PWS locus of 12 mammalian genomes and their evolution processes. A total of 613 imprinted snoRNAs were identified in the PWS homologous loci and the gene number was highly variable across lineages, with a peak in Euarchontoglires. Lineage-specific gene gain and loss events account for most extant genes of the HBII-52 (SNORD115) and the HBII-85 (SNORD116) gene family, and remarkable high gene-birth rates were observed in the primates and the rodents. Meanwhile, rapid sequence substitution occurred only in imprinted snoRNA genes, rather than their flanking sequences or the protein-coding genes located in the same imprinted locus. Strong selective constraints on the functional elements of these imprinted snoRNAs further suggest that they are subjected to birth-and-death evolution. Our data suggest that the regulatory role of HBII-52 on 5-HT2CR pre-mRNA might originate in the Euarchontoglires through adaptive process. We propose that the rapid evolution of PWS-related imprinted snoRNAs has contributed to the neural development of Euarchontoglires.