Immunogenicity and safety of a severe acute respiratory syndrome coronavirus 2 inactivated vaccine in healthy adults: randomized, double-blind, and placebo-controlled phase 1 and phase 2 clinical trials

Background:The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)call for urgent development of effective and safe vaccines.We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine,KCONVAC,in healthy adults.Methods:Phase 1 and phase 2 randomized,double-blind,and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years.The participants in the phase 1 trial were randomized to receive two doses,one each on Days 0 and 14,of either KCONVAC(5 or 10 mg/dose)or placebo.The participants in the phase 2 trial were randomized to receive either KCONVAC(at 5 or 10 mg/dose)or placebo on Days 0 and 14(0/14 regimen)or Days 0 and 28(0/28 regimen).In the phase 1 trial,the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose.In the phase 2 trial,the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose.Results:Inthe phase1 trial,60 participantswere enrolled andreceived at least one dose of 5-mgvaccine(n=24),10-mgvaccine(n=24),or placebo(n=12).In the phase 2 trial,500 participantswere enrolled and received at least one dose of 5-mg vaccine(n=100 for 0/14 or 0/28 regimens),10-mg vaccine(n=100 for each regimen),or placebo(n=50 for each regimen).In the phase 1 trial,13(54%),11(46%),and seven(7/12)participants reported at least one adverse event(AE)after receiving 5-,10-mg vaccine,or placebo,respectively.In the phase 2 trial,16(16%),19(19%),and nine(18%)0/14-regimen participants reported at least oneAEafter receiving 5-,10-mg vaccine,or placebo,respectively.Similar AE incidences were observed in the three 0/28-regimen treatment groups.No AEs with an intensity of grade 3+were reported,expect for one vaccine-unrelated seriousAE(foot fracture)reported in the phase 1 trial.KCONVACinduced significant antibody responses;0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses.Conclusions:Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults.These results support testing 5-mg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial.Trial Registration:http://www.chictr.org.cn/index.aspx(No.ChiCTR2000038804,http://www.chictr.org.cn/showproj.aspx?proj=62350;No.ChiCTR2000039462,http://www.chictr.org.cn/showproj.aspx?proj=63353).

Real-time reverse transcription-polymerase chain reaction assay panel for the detection of severe acute respiratory syndrome coronavirus 2 and its variants

Background:With the ongoing worldwide coronavirus disease 2019(COVID-19)pandemic,an increasing number of viral variants are being identified,which poses a challenge for nucleic acid-based diagnostic tests.Rapid tests,such as real-time reverse transcription-polymerase chain reaction(rRT-PCR),play an important role in monitoring COVID-19 infection and controlling its spread.However,the changes in the genotypes of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants may result in decreased sensitivity of the rRT-PCR assay and it is necessary to monitor the mutations in primers and probes of SARSCoV-2 detection over time.Methods:We developed two rRT-PCR assays to detect the RNA-dependent RNA polymerase(RdRp)and nucleocapsid(N)genes of SARS-CoV-2.We evaluated these assays together with our previously published assays targeting the ORF1ab and N genes for the detection and confirmation of SARS-CoV-2 and its variants of concern(VOCs).In addition,we also developed two rRT-PCR assays(S484K and S501Y)targeting the spike gene,which when combined with the open reading frames(ORF)1ab assay,respectively,to form duplex rRT-PCR assays,were able to detect SARS-CoV-2 VOCs(lineages B.1.351 and B.1.1.7).Results:Using a SARS-CoV-2 stock with predetermined genomic copies as a standard,the detection limit of both assays targeting RdRp and N was five copies/reaction.Furthermore,no cross-reactions with six others human CoVs(229E,OC43,NL63,HKU1,severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus)were observed using these assays.In addition,the S484K and S501Y assays were combined with the ORF1ab assay,respectively.Conclusions:Four rRT-PCR assays(RdRp,N,S484K,and S501Y)were used to detect SARS-CoV-2 variants,and these assays were shown to be effective in screening for multiple virus strains.