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The SARS-CoV-2 non-Spike (S) structural protein targets of nucleocapsid (N), membrane (M) and envelope (E), critical in the host cell interferon response and memory T-cell immunity, have been grossly overlooked since the inception of COVID vaccine development. To pursue a universal (pan-sarbecovirus) vaccine against ever-emergent future mutants, we explored booster immunogenicity of UB-612, a multitope-vaccine that contains S1-RBD-sFc protein and sequence-conserved rationally designed promiscuous Th and CTL epitope peptides on the Sarbecovirus N, M and S2 proteins. To a subpopulation of infection-free participants (aged 18-85 years) involved in a two-dose Phase-2 trial, a UB-612 booster (third dose) was administered 6-8 months after the second dose. The immunogenicity was evaluated at 14 days post-booster with overall safety monitored until the end of study. The booster induced high viral-neutralizing antibodies against live Wuhan WT (VNT50, 1,711) and Delta (VNT50, 1,282); and against pseudovirus WT (pVNT50, 11,167) vs. Omicron BA.1/BA.2/BA.5 variants (pVNT50, 2,314/1,890/854), respectively. The lower primary neutralizing antibodies in the elderly were uplifted upon boosting to approximately the same high level in young adults. UB-612 also induced potent, durable Th1-oriented (IFN-γ+-) responses (peak/pre-boost/post-boost SFU/106 PBMCs, 374/261/444) along with robust presence of cytotoxic CD8+ T cells (peak/pre-boost/post-boost CD107a+-Granzyme B+, 3.6%/1.8%/1.8%). Booster vaccination is safe and well tolerated without SAEs. By recognition against epitopes on Spike (S1-RBD and S2) and non-Spike (N and M) structure proteins, UB-612 provides potent, broad and long-lasting B-cell and T-cell memory immunity and offers a potential as a universal vaccine to fend off Omicrons and new VoCs.SIGNIFICANCE STATEMENTThe Omicron has swept the globe with a rapid succession of dominating sublineages from BA.1, BA.2, to the current BA.5 with increasing infectivity and antibody evasion. Concerningly, the non-Spike structure proteins that promote T-cell immunity are grossly overlooked in vaccine development. Looking beyond short-interval booster jabs and omicron-updated vaccines, a pragmatic approach to curbing ever-emergent new mutants would be “universal (pan-Sarbecovirus) vaccines” targeting conserved nonmutable epitopes on coronavirus. UB-612, a multitope-vaccine armed with Spike (S1-RBD and S2) and non-Spike targets (Nucleocapsid N and Membrane M), allows booster vaccination to elicit potent, broadly-recognizing, durable B- and T-cell memory immunity. Sequence-conserved epitope peptides were rationally-designed from S2, N and M proteins to synergistically enhance memory helper and cytotoxic T-cell immunity and B-cell immunity.

The 2009 influenza pandemic provided an opportunity to observe dynamic changes of the hemagglutinin (HA) and neuraminidase (NA) of pH1N1 strains that spread in two metropolitan areas--Taipei and Kaohsiung. We observed cumulative increases of amino acid substitutions of both HA and NA that were higher in the post-peak than in the pre-peak period of the epidemic. About 14.94% and 3.44% of 174 isolates had one and two amino acids changes, respective, in the four antigenic sites. One unique adaptive mutation of HA2 (E374K) was first detected three weeks before the epidemic peak. This mutation evolved through the epidemic, and finally emerged as the major circulated strain, with significantly higher frequency in the post-peak period than in the pre-peak (64.65% vs 9.28%, p

Background The heptavalent pneumococcal conjugate vaccine was introduced in Taiwan in October 2005. To evaluate the effect of the vaccination, we conducted an active, prospective, large-scale, long-term, and multicenter study to assess the prevalence of nasopharyngeal Streptococcus pneumoniae carriage in Taiwanese children. Methods This study was performed at three tertiary teaching hospitals in northern, central, and southern Taiwan. Questionnaires provided demographic, family/household, and medical history data. Pneumococcal isolates were tested for their susceptibility to various antimicrobial agents and serotypes. In addition, influenza virus and Staphylococcus aureus were recovered from nasopharyngeal and nasal swabs, respectively. Results Between July 2005 and July 2008, 857 pneumococcal strains were recovered from a total of 6057 children aged >2 months to 5 years (carriage rate, 14.1%). Carriage rates differed geographically and varied with subject age. In a multivariate analysis, having at least one sibling, attendance at day-care centers, a history of otitis media, and history of upper respiratory tract infection in the previous 2 weeks were each associated with a higher risk of pneumococcal colonization of the nasopharynx. Staphylococcus aureus nasal colonization was inversely associated with nasopharyngeal carriage of pneumococcus ( p = 0.000; odds ratio [OR]: 0.48; 95% CI: 0.39–0.58). Daycare attendance was the only risk factor for carriage of penicillin non-susceptible S. pneumoniae (OR: 2.37; 95% CI: 1.22–4.88). Although vaccination rates rose from 2005 to 2008, no concomitant decrease in S. pneumoniae carriage occurred. The rate of penicillin resistance among S. pneumoniae isolates was 92.8% (using the meningitis criteria). The prevalence of cefotaxime resistance (21.6%) was higher than that of penicillin (6.9%; non-meningitis criteria). Slightly more than half (57.4%) of the isolates belonged to strains covered by the heptavalent pneumococcal conjugate vaccine when both vaccine and vaccine-related serotypes were included. Conclusions Although vaccination rates rose from 2005 to 2008, no concomitant decrease occurred in S. pneumoniae carriage. Interaction between S. aureus and S. pneumoniae may influence vaccination efficacy. These findings provide baseline data to further compare pneumococcal carriage rates and antibiotic resistance patterns in Taiwanese children as vaccination rates continue to increase.

To compare the antimicrobial activities of ertapenem, ciprofloxacin, ceftriaxone, piperacillin-tazobactam, and ampicillin-sulbactam against 12 common organisms that cause community-acquired bacteremia and to identify the most active agents for the treatment of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae.1200 blood specimens from patients with community-acquired bacteremia were collected at Chang Gung Memorial Hospital, Kaohsiung, Taiwan. All isolates were identified by the API system, and each culture's antimicrobial susceptibility was determined by the standard disk-diffusion method. The minimal inhibitory concentrations of the antibiotics were detected by the Epsilimeter test.The in vitro susceptibilities of 11 of the 12 common pathogens to ertapenem were 100%. The frequency of ESBL-producing E. coli and K. pneumoniae was 6.2% and 9.5%, respectively. Only 48% and 50% of E. coli and K. pneumoniae, respectively, were susceptible to ciprofloxacin. These data infer that ciprofloxacin should not be given for ESBL-producing E. coli and K. pneumoniae. Ceftriaxone and piperacillin-tazobactam had high activity against the most common pathogens isolated.ESBL E. coli and K. pneumoniae are highly resistant to ciprofloxacin, so this antibiotic should be avoided for patients with community-acquired bacteremia. ESBL E. coli and K. pneumoniae are highly susceptible to ertapenem.

Parapneumonic effusion and empyema are recognized complications of bacterial pneumonia. Optimal management in children, especially the duration of parenteral antibiotics and the role of surgery, is controversial. This study analyzed the clinical characteristics, management, outcome, and bacterial etiology of 59 patients with complicated parapneumonic effusion and empyema treated at a single medical center in Kaohsiung from January 1995 to March 2004.The diagnosis of complicated parapneumonic effusion was based on the specific characteristics of pleural fluid, computed tomography or ultrasound findings, or direct visualization of loculations during the surgical procedure.Causative agents were culture-confirmed in 42% of the cases. Streptococcus pneumoniae was the leading pathogen in this series (20% of cases). None of the S. pneumoniae isolates were susceptible to penicillin. Mycoplasma pneumoniae accounted for 19% of cases based on immunoglobulin M assay.An initial combination therapy regimen consisting of cefotaxime or ceftriaxone plus macrolide provided reasonable activity against 80% of the pathogens isolated in this series. This study also revealed that prolonged parenteral antibiotic treatment resulted in longer length of hospital stay.

Background/PurposeInfections caused by extended-spectrum β-lactamase (ESBL)-producing bacteria have become a serious clinical concern worldwide. The occurrence of ESBLs in Taiwan has been well-documented and is reviewed in recent publications. However, studies comparing community-onset bacteremia caused by ESBL- and non-ESBL-producing Escherichia coli are limited.MethodsWe retrospectively reviewed the medical records of patients with E. coli bacteremia who visited the emergency department of Kaohsiung Chang Gung Memorial Hospital from January 2005 to December 2006. Clinical data were collected to compare the clinical features of patients with ESBL-producing E. coli with those of patients with non-ESBL-producers and to identify the risk factors associated with ESBL-producing E. coli bacteremia.ResultsThere were 404 episodes of community-onset E. coli bacteremia. The overall 30-day mortality rate was 11.4% (46/404) and the mortality rate of healthcare-associated infections was significantly higher than that of community-acquired infections [4/13 (30.8%) vs. 42/391 (10.7%); p= 0.049] Nonurinary focus was independently associated with an increased risk of fatality [47/178 (26.4%) vs. 4/226 (1.8%); p < 0.001]. The frequency of ESBL producers was 4.7% (19/404). Of these, four (21.1%) were associated with a long-term care facility. Significant risk factors associated with ESBL-producing E. coli bacteremia included recent antibiotic exposure (within 30 days) and urinary catheter placement. Although the trend was towards higher mortality in patients with ESBL-producing E. coli bacteremia, the difference did not reach statistical significance compared with the mortality of patients with non-ESBL E. coli bacteremia.ConclusionFewer than 5% of community-onset E. coli bacteremia episodes in Southern Taiwan were due to ESBL-producers. Prior antibiotic use within 30 days and urinary catheter placement were independently associated with ESBL-producing E. coli bacteremia.