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Background: The SARS-CoV-2 non-Spike (S) structural protein targets on nucleocapsid (N), membrane (M) and envelope (E), critical in the host cell interferon response and memory T-cell immunity, are grossly overlooked in COVID vaccine development. The current Spike-only vaccines bear an intrinsic shortfall for promotion of a fuller T cell immunity. Vaccines designed to target conserved epitopes could elicit strong cellular immune responses that would synergize with B cell responses and lead to long-term vaccine success. We pursue a universal (pan-SARS-CoV-2) vaccine against Delta, Omicrons and ever-emergent new mutants. Methods and findings: We explored booster immunogenicity of UB-612, a multitope-vaccine that contains S1-RBD-sFc protein and sequence-conserved promiscuous Th and CTL epitope peptides on the Sarbecovirus N, M and S2 proteins. To a subpopulation (N = 1,478) 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%). This UB-612 booster vaccination is safe and well tolerated without SAEs. Conclusions: By targeting conserved epitopes on viral S2, M and N proteins, UB-612 could provide potent, broad and long-lasting B-cell and T-cell memory immunity and offers the potential as a universal vaccine to fend off Omicrons and new VoCs without resorting to Omicron-specific immunogens. Trial registration: ClinicalTrials.gov: NCT04773067; ClinicalTrials.gov ID: NCT05293665; ClinicalTrials.gov ID: NCT05541861. Author summary: The Omicron variant of SARS-CoV-2 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 have been grossly overlooked in vaccine development. Looking beyond short-interval boosters and omicron-updated vaccines, a pragmatic approach to curbing ever-emergent new mutants would be "universal (pan-SARS-CoV-2) vaccines" as exemplified by UB-612, a multitope-vaccine armed with Spike (S1-RBD and S2) and non-Spike (Nucleocapsid N and Membrane M) targets, allowing booster vaccination to elicit broadly-recognizing and durable B-/T-cell memory immunity. Sequence-conserved Th/CTL epitope peptides were designed from S2, N and M proteins to synergistically enhance memory helper and cytotoxic T-cell immunity and RBD targeted B-cell immunity. [ABSTRACT FROM AUTHOR]

Background: The clinical characteristics and outcomes of the 2019 novel coronavirus (COVID-19) pneumonia are different in Hubei compared to other regions in China. But there are few comparative studies on the differences between imported and local patients which may provide information of the different courses of the virus after transmission.Methods: We investigated 169 cases of COVID-19 pneumonia in two centers in Hunan Province, and divided them into two groups according to epidemiological history, "imported patients" refers to patient with a clear history of travel in Wuhan within 14 days before onset, and " local patients" refers to local resident without a recent history of travel in Wuhan, aiming to analyze the difference in clinical characteristics and outcomes between the two groups. All the epidemiological, clinical, imaging, and laboratory data were analyzed and contrasted.Results: The incidence of fever on admission in imported patients was significantly higher than local patients. There was a significantly higher proportion of abnormal pulmonary signs, hypokalemia, hyponatremia, prolonged PT, elevated D-dimer and elevated blood glucose in imported patients. Compared with local patients, the proportion using antibiotics, glucocorticoids and gamma globulin were significantly higher in imported patients. The moderate type was more common in local patients, and the severe type were more frequent in imported patients. In addition, the median duration of viral clearance was longer in imported patients.Conclusions: In summary, we found that imported cases were more likely to develop into severe cases, compared with local patients and required more powerful treatments. Trial registration Registered 21st March 2020, and this study has been approved by the Medical Ethics Committee (Approved Number. 2020017). [ABSTRACT FROM AUTHOR]