Safety and immunogenicity of Nanocovax, a SARS-CoV-2 recombinant spike protein vaccine: Interim results of a double-blind, randomised controlled phase 1 and 2 trial.

Background: Nanocovax is a recombinant severe acute respiratory syndrome coronavirus 2 subunit vaccine composed of full-length prefusion stabilized recombinant SARS-CoV-2 spike glycoproteins (S-2P) and aluminium hydroxide adjuvant. Methods: We conducted a dose-escalation, open label trial (phase 1) and a randomized, double-blind, placebo-controlled trial (phase 2) to evaluate the safety and immunogenicity of the Nanocovax vaccine (in 25 mcg, 50 mcg, and 75 mcg doses, aluminium hydroxide adjuvanted (0·5 mg/dose) in 2-dose regime, 28 days apart (ClinicalTrials.gov number, NCT04683484). In phase 1, 60 participants received two intramuscular injection of the vaccine following dose-escalation procedure. The primary outcomes were reactogenicity and laboratory tests to evaluate the vaccine safety. In phase 2, 560 healthy adults received either vaccine doses similar in phase 1 (25 or 50 or 75 mcg S antigen in 0·5 mg aluminium per dose) or adjuvant (0·5 mg aluminium) in a ratio of 2:2:2:1. One primary outcome was the vaccine safety, including solicited adverse events for 7 day and unsolicited adverse events for 28 days after each injection as well as serious adverse event or adverse events of special interest throughout the study period. Another primary outcome was anti-S IgG antibody response (Index unit/ml). Secondary outcomes were surrogate virus neutralisation (inhibition percentage), wild-type SARS-CoV-2 neutralisation (dilution fold), and T-cell responses by intracellular staining for interferon gamma (IFNg). Anti-S IgG and neutralising antibody levels were compared with convalescent serum samples from symptomatic Covid-19 patients. Findings: For phase 1 study, no serious adverse events were observed for all 60 participants. Most adverse events were grade 1 and disappeared shortly after injection. For phase 2 study, after randomisation, 480 participants were assigned to receive the vaccine with adjuvant, and 80 participants were assigned to receive the placebo (adjuvant only). Reactogenicity was absent or mild in the majority of participants and of short duration (mean ≤3 days). Unsolicited adverse events were mild in most participants. There were no serious adverse events related to Nanocovax. Regarding the immunogenicity, Nanocovax induced robust anti-S antibody responses. In general, there humoral responses were similar among vaccine groups which reached their peaks at day 42 and declined afterward. At day 42, IgG levels of vaccine groups were 60·48 [CI95%: 51·12-71·55], 49·11 [41·26-58·46], 57·18 [48·4-67·5] compared to 7·10 [6·32-13·92] of convalescent samples. IgG levels reported here can be converted to WHO international standard binding antibody unit (BAU/ml) by multiplying them to a conversion factor of 21·8. Neutralising antibody titre of vaccine groups at day 42 were 89·2 [52·2-152·3], 80·0 [50·8-125.9] and 95·1 [63·1-143·6], compared to 55·1 [33·4-91·0] of the convalescent group. Interpretation: Up to day 90, Nanocovax was found to be safe, well tolerated, and induced robust immune responses. Funding: This work was funded by the Coalition for Epidemic Preparedness Innovations (CEPI), the Ministry of Science and Technology of Vietnam, and Nanogen Pharmaceutical Biotechnology JSC.

Genome-wide analysis of SARS-CoV-2 strains circulating in Vietnam: Understanding the nature of the epidemic and role of the D614G mutation.

Genome-wide analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains is essential to better understand infectivity and virulence and to track coronavirus disease 2019 (COVID-19) cases and outbreaks. We performed whole-genome sequencing of 27 SARS-CoV-2 strains isolated between January 2020 and April 2020. A total of 54 mutations in different genomic regions was found. The D614G mutation, first detected in March 2020, was identified in 18 strains and was more likely associated with a lower cycle threshold (<25) in real-time reverse-transcription polymerase chain reaction diagnostic tests than the original D614 (prevalence ratio = 2.75; 95% confidence interval, 1.19-6.38). The integration of sequencing and epidemiological data suggests that SARS-CoV-2 transmission in both quarantine areas and in the community in Vietnam occur at the beginning of the epidemic although the country implemented strict quarantine quite early, with strict contact tracing, and testing. These findings provide insights into the nature of the epidemic, as well as shape strategies for COVID-19 prevention and control in Vietnam.

Clinical features, isolation, and complete genome sequence of severe acute respiratory syndrome coronavirus 2 from the first two patients in Vietnam.

In January 2020, we identified two severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients in a familial cluster with one person coming from Wuhan, China. The complete genome sequences of two SARS-CoV-2 strains isolated from these patients were identical and 99.98% similar to strains isolated in Wuhan. This is genetically suggestive of human-to-human transmission of SARS-CoV-2 and indicates Wuhan as the most plausible origin of the early outbreak in Vietnam. The younger patient had a mild upper respiratory illness and a brief viral shedding, whereas the elderly with multi-morbidity had pneumonia, prolonged viral shedding, and residual lung damage. The evidence of nonsynonymous substitutions in the ORF1ab region of the viral sequence warrants further studies.