In a phase3trial conducted in the United States,Argentina,Brazil,South Africa,Germany,and Turkey,the BioNTech-Pfizer mRNA vaccine BNT162b2was95%effective in preventing COVID-19through the data cutoff date of 14November2020(1个)。The severe acute respiratory syndrome coronavirus2(SARS-CoV-2)lineage B.1.1.7(variant of concern:VOC202012/01)was discovered to have emerged in the United Kingdom in September2020(2),以及it subsequently increased in prevalence,showed enhanced transmissibility,and spread to other countries and continents(3)。B.1.1.7 has a series of mutations in its spike(S)protein:ΔH69/V70,ΔY144,N501Y,A570D,D614G,P681H,T716I,S982A,and D1118H(H,His;V,Val;Y,Tyr;N,Asn;A,Ala;D,Asp;G,Gly;P,Pro;T,Thr;I,Ile;S,Ser。One of these mutations,N501Y,was of particular concern because it is located in the receptor binding site.The spike with this mutation binds more tightly to its cellreceptor,ACE-24个),and virus with this mutation has an increased host range that includes mice(5)。BNT162b2-immune sera neutralized SARS-Cov-2(USA/WA-1/2020background strain)with an introduced N501Y mutation asefficiently as they neutralized SARS-Cov-2without the mutation(6个)。Further,19pseudoviruses,each bearing a SARS-CoV-2S with a different mutation found in circulating virus strains,were also neutralized as efficiently as nonmutant SARS-CoV-2S-bearing pseudoviruses by BNT162b2-immune sera(7)。However,it was still unclear wherus with the full set of mutations in the lineage B.1.1.7spike,each of which may potentially interfere with antibody binding,would be neutralized efficiently by BNT162b2-immune sera。
To answer this question,we generated vesicular stomatitis virus(VSV)–SARS-Cov-2-Spseudoviruses bearing the Wuhan reference strain or the lineage B.1.1.7 spike protein(fig.S1)。40 participants in the previously reported German phase1/2 trial(7)-drawn from26younger(aged23to55years)and14older adults(aged57to73years)at7or21days after the booster immunization with30μg of BNT162b2(pVNT)50)]。The50%neutralization geometric mean titers(GMTs)of the sera against the SARS-CoV-2lineage B.1.1.7 spike–pseudotyped VSV for the younger adult group and the full analysis set were slightly but statistically significantly reduced compared with the GMTs against the Wuhan reference spike–Sudeand table S1.GMTs were not significantly different for the older adult group.The calculated geometric mean ratio with95%confidence interval(CI)of the B.1.1.7 pseudotype and the Wuhan pseudotype GMTs was0.78(95%CI:0.68to0.89)for the younger group and 0.83(95%CI:0.65to)for to 0.89)in aggregate]()。No statistical difference in the ratio was observed between the younger and the older vaccinated participants。
50%pseudovirus neutralization titers(pVNT)50)of40sera from BNT162b2vaccine recipients against VSV-SARS-CoV-2-S pseudovirus bearing the Wuhan reference strain or lineage B.1.1.7 spike protein。Sera fromn=26 younger adults(aged23to55 years;按索引排列和n=14older adults(aged57 to 73years;indicated by circles)drawn at either day29 or day43(7or21 days after vaccine dose two)were tested。Statistical significance of the difference between the neutralization of the VSV-SARS-COV-2-Spseudovirus bearing the Wuhan or lineage B.1.1.7 spike protein was calculated bya Wilcoxon matched-pairs signed rank test.Two-tailedPvalues are reported.GMTs and 95%CIs are indicated。
pVNT50ratio of SARS-CoV-2 lineage B.1.1.7to Wuhan reference strain spike–pseudotyped VSV。Triangles represent sera from younger adults(aged23to55years),and circles represent sera from older adults(aged57to73years)。Sera were drawn on either day29 or day43(7or21 days after vaccine dose two)。Geometric means of the pVNT50ratios of SARS-CoV-2lineage B.1.1.7 to Wuhan spike–pseudotyped VSV and 95%CIs are indicated.The difference in distribution of titer ratios between younger and older adults was tested for statistical significance with a two-tailed Mann-WhitneyUtest。
influenza virus vaccines,a20%reduced titer does not indicate a biologically relevant change in neutralization activity(8个单击功能区上,9)。The largely preserved neutralization of pseudoviruses bearing the B.1.1.7 spike by BNT162b2-immune sera makes it unlikely that the U.K.variant virus will escape BNT162b2-mediated protection。
A potential limitation of the work may be the use of anonreplicating pseudovirus system.However,previous reports have shown good concordance between pseudotype neutralization and SARS-CoV-2neutralization assays(10单击功能区上,11)。Still, concordance may vary between different SARS-CoV-2strains and remains to be demonstrated for the SARS-CoV-2B.1.1.7 lineage.Additional experiments will be needed to confirm efficient neutralization of B.1.1.7 lineage clinical isolates.This study has evaluated sera elicited by the recommended regimendes of aminical inical isolates.This study has evalisted sera and does not provide insight into neutralization if the recommended dosing regimen is not followed.The ongoing evolution of SARS-CoV-2necessitates continuous monitoring of the biological relevance of changes for maintained protection by the currently authorized vaccines.Unlike the protocol for influenza vaccines,the degree of reduction in neutralization that might indicate a need for astrain change has not yet been established for COVID-19vaccines.A previous study demonstrated that BNT162b2elicits both a polyepitopic CD8+T cell responsse to the encoded spike protein and virus-neutrazing7)。Given the multiple potential mediators of protection elicited by BNT162b2,it is possible that vaccine efficicacy could be preserved in the longer term,even with substantial losses of neutralization by vaccine-elicited sera.This view is further supported by the rapid onset of disease protection~12days the dors2 of,预应力混凝土预应力桩1个)。Without an established correlate of protection,clinical effectiveness data will be needed to provide definitive assessment of vaccine-mediated protection against viral variants。
Although sustained neutralization of the current B.1.1.7 variant is reasuring,preparation for potential COVID-19vaccine strain change is prudent.Adaptation of the vaccine to a new virus strain would be facilitated by the flexibility of mRNA-based vaccine technology。