Background
The Delta and Omicron variants of SARS-CoV-2 are currently responsible for breakthrough infections due to waning immunity. We report phase I/II trial results of UB-612, a multitope subunit vaccine containing S1-RBD-sFc protein and rationally designed promiscuous peptides representing sarbecovirus conserved helper T cell and cytotoxic T lymphocyte epitopes on the nucleocapsid (N), membrane (M), and spike (S2) proteins.
Method
We conducted a phase I primary 2-dose (28 days apart) trial of 10, 30, or 100 μg UB-612 in 60 healthy young adults 20 to 55 years old, and 50 of them were boosted with 100 μg of UB-612 approximately 7 to 9 months after the second dose. A separate placebo-controlled and randomized phase II study was conducted with 2 doses of 100 μg of UB-612 (
n =
3,875, 18–85 years old). We evaluated interim safety and immunogenicity of phase I until 14 days after the third (booster) dose and of phase II until 28 days after the second dose.
Results
No vaccine-related serious adverse events were recorded. The most common solicited adverse events were injection site pain and fatigue, mostly mild and transient. In both trials, UB-612 elicited respective neutralizing antibody titers similar to a panel of human convalescent sera. The most striking findings were long-lasting virus-neutralizing antibodies and broad T cell immunity against SARS-CoV-2 variants of concern (VoCs), including Delta and Omicron, and a strong booster-recalled memory immunity with high cross-reactive neutralizing titers against the Delta and Omicron VoCs.
Conclusion
UB-612 has presented a favorable safety profile, potent booster effect against VoCs, and long-lasting B and broad T cell immunity that warrants further development for both primary immunization and heterologous boosting of other COVID-19 vaccines.
Trial Registration
ClinicalTrials.gov: NCT04545749, NCT04773067, and NCT04967742.
Funding
UBI Asia, Vaxxinity Inc., and Taiwan Centers for Disease Control, Ministry of Health and Welfare.
Congestive heart failure and metastatic infections were predictors of mortality. Isolates with decreased susceptibility to vancomycin that emerged during persistent MRSA bacteraemia were associated with mortality. Aggressive attempts to completely eradicate foci should be encouraged.
We collected 110 Salmonella enterica isolates from sick pigs and determined their serotypes, genotypes using pulsed-field gel electrophoresis (PFGE), and antimicrobial susceptibility to 12 antimicrobials and compared the data with a collection of 18,280 isolates obtained from humans. The pig isolates fell into 12 common serovars for human salmonellosis in Taiwan; S. Typhimurium, S. Choleraesuis, S. Derby, S. Livingstone, and S. Schwarzengrund were the 5 most common serovars and accounted for a total of 84% of the collection. Of the 110 isolates, 106 (96%) were multidrug resistant (MDR) and 48 (44%) had PFGE patterns found in human isolates. S. Typhimurium, S. Choleraesuis, and S. Schwarzengrund were among the most highly resistant serovars. The majority of the 3 serovars were resistant to 8–11 of the tested antimicrobials. The isolates from pigs and humans sharing a common PFGE pattern displayed identical or very similar resistance patterns and Salmonella strains that caused severe infection in pigs were also capable of causing infections in humans. The results indicate that pigs are one of the major reservoirs to human salmonellosis in Taiwan. Almost all of the pig isolates were MDR, which highlights the necessity of strictly regulating the use of antimicrobials in the agriculture sector in Taiwan.
In Taiwan, the 23-valent pneumococcal polysaccharide vaccine (PPV23) and the 7-valent pneumococcal conjugate vaccine (PCV7) have been available since January 2001 and October 2005, respectively. A hospital-based surveillance of invasive pneumococcal disease (IPD) in a medical center was conducted from 2000 to 2008 to evaluate the epidemiologic changes after pneumococcal vaccination. A total of 337 episodes in 328 patients were identified. The cumulative coverage rate of PPV23 among persons of age >or=75 years increased from 12% in 2007 to 41% in 2008, and that of PCV7 among children aged <5 years was 0.7% in 2005 and 25.2% in 2008. The annual incidence of IPD decreased from 6.2 cases per 10,000 hospitalizations in 2000-2005 to 3.8 cases in 2006-2008 (38.5% reduction, P < 0.001), but the fatality rate did not change significantly (24.4% and 21.8%, P = 0.74). The serotype coverage rates of PPV23 and PCV7 were not significantly different between 2000-2005 and 2006-2008 (both P > 0.05). A marked increase of serotype 19A from 2000-2005 (0.5%) to 2006-2008 (11.5%) was found (P < 0.001). In summary, a decline in IPD incidence but not in fatality rate occurred after the availability of PCV7 and the increased usage of PPV23. The rapid emergence of serotype 19A during this period is alarming.
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