Durability of mRNA-1273 vaccine–induced antibodies against SARS-CoV-2 variants
Amarendra PeguSarah O’ConnellStephen D. SchmidtSijy O’DellChloe Adrienna TalanaLilin LaiJim AlbertEvan J. AndersonHamilton BennettKizzmekia S. CorbettBritta FlachLisa A. JacksonBrett LeavJulie E. LedgerwoodCatherine J. LukeMat MakowskiMartha NasonPaul C. RobertsMario RoedererPaulina A. RebolledoChristina A. RostadNadine RouphaelWei ShiLingshu WangAlicia T. WidgeEun Sung YangJohn H. BeigelBarney S. GrahamJohn R. MascolaMehul S. SutharAdrian B. McDermottNicole A. Doria‐RoseJae AregaJohn H. BeigelWendy BuchananMohammed ElsafyBinh HoangRebecca LampleyAparna KolhekarHyung Il KooCatherine J. LukeMamodikoe MakheneSeema NayakRhonda Pikaart-TautgesPaul C. RobertsJanie RussellElisa SindallJim AlbertPratap KunwarMat MakowskiEvan J. AndersonAmer BechnakMary BowerAndrés Camacho-GonzálezMatthew H. CollinsAna DrobeniucVenkata Viswanadh EdaraSrilatha EdupugantiKatharine FloydTheda GibsonCassie M. Grimsley AckerleyBrandi JohnsonSatoshi KamidaniCarol KaoColleen F. KelleyLilin LaiHollie MacenczakMichele Paine McCulloughEtza PetersVarun K. PhadkePaulina A. RebolledoChristina A. RostadNadine RouphaelErin M. SchererAmy C ShermanKathy StephensMehul S. SutharMehgan TeheraniJessica TraenknerJuton Winstonİnci YıldırımLee BarrJoyce BenoitBarbara CarsteJoe ChoeMaya DunstanRoxanne ErolinJana ffitchColin FieldsLisa A. JacksonErika KinirySusan LasickaStella E. LeeM. NguyenStephanie PimientaJanice SuyehiraMichael M. WitteHamilton BennettNedim Emil AltarasAndrea Carfı́Marjorie HurleyBrett LeavRolando PajónWellington SunTal ZaksRhea N. ColerSasha E. LarsenKathleen M. NeuzilLisa C. LindesmithDavid R. MartinezJennifer E. MuntMichael L. MalloryCaitlin E. EdwardsRalph S. BaricNina M. BerkowitzEli BoritzKevin CarltonKizzmekia S. CorbettPamela CostnerAdrian CreangaNicole A. Doria‐RoseDaniel C. DouekBritta FlachMartin R. GaudinskiIngelise J. GordonBarney S. GrahamLaSonji A. HolmanJulie E. LedgerwoodKwanyee LeungBob C. LinMark K. LouderJohn R. MascolaAdrian B. McDermottKaitlyn M. MorabitoLaura NovikSarah O’ConnellSijy O’DellMarcelino PadillaAmarendra PeguStephen D. SchmidtWei ShiPhillip A. SwansonChloe Adrienna TalanaLingshu WangAlicia T. WidgeEun Sung YangYi ZhangJames D. ChappellMark R. DenisonTia M. HughesXiaotao LuAndrea J. PruijssersLaura J. StevensChristine M. PosavadMichael GaleVineet D. MenacheryPei‐Yong Shi
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutations may diminish vaccine-induced protective immune responses, particularly as antibody titers wane over time. Here, we assess the effect of SARS-CoV-2 variants B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.429 (Epsilon), B.1.526 (Iota), and B.1.617.2 (Delta) on binding, neutralizing, and angiotensin-converting enzyme 2 (ACE2)–competing antibodies elicited by the messenger RNA (mRNA) vaccine mRNA-1273 over 7 months. Cross-reactive neutralizing responses were rare after a single dose. At the peak of response to the second vaccine dose, all individuals had responses to all variants. Binding and functional antibodies against variants persisted in most subjects, albeit at low levels, for 6 months after the primary series of the mRNA-1273 vaccine. Across all assays, B.1.351 had the lowest antibody recognition. These data complement ongoing studies to inform the potential need for additional boost vaccinations.Objective To analyze the distribution and persistence of neutralizing antibody titer against human cytomegalovirus(HCMV) in plasma donors in Sichuan Province,China.Methods A total of 2 002 serum samples of health plasma donors were collected from 8 plasma stations in Sichuan Province and determined for neutralizing antibody titer by developed method,based on which the samples from 44 donors were traced for one year,and those from one donor for 4 years.Results The neutralizing antibody titers against HCMV in plasma donors in Sichuan Province were mainly distributed in 1 ∶ 16 ～ 1 ∶ 64,while the positive rate(not less than 1 ∶ 8) was 98.35%,of which 8.04% were not less than 1 ∶ 192.The neutralizing antibody titers of 44 plasma donors were stable within the past one year.However,the neutralizing antibody titers of the donors traced for 4 years were maintained at high levels.Conclusion The natural infection rate of HCMV was high in plasma donors in Sichuan Province.The HCMV neutralizing antibody titers were high and persistent in partial donors.It provided a basis for preparation of HCMV-specific IgG.
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Cytomegalovirus
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Canine distemper
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Abstract The World Health Organization (WHO) has highlighted the importance of an international standard (IS) for SARS-CoV-2 neutralizing antibody titer detection, with the aim of calibrating different diagnostic techniques. In this study, IS was applied to calibrate neutralizing antibody titers (IU/mL) and binding antibody titers (BAU/mL) in response to SARS-CoV-2 vaccines. Serum samples were collected from participants receiving the Moderna (n = 20) and Pfizer (n = 20) vaccines at three time points: pre-vaccination, after one dose, and after two doses. We obtained geometric mean titers of 1404.16 and 928.75 IU/mL for neutralizing antibodies after two doses of the Moderna and Pfizer vaccines, respectively. These values provide an important baseline for vaccine development and the implementation of non-inferiority trials. We also compared three commercially available kits from Roche, Abbott, and MeDiPro for the detection of COVID-19 antibodies based on binding affinity to S1 and/or RBD. Our results demonstrated that antibody titers measured by commercial assays are highly correlated with neutralizing antibody titers calibrated by IS.
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An immune response to recombinant human protein therapeutics, including type I interferons (IFNs), has the potential to have a serious negative impact on safety and efficacy. Monitoring of patients for neutralizing antibodies (NAbs) often is advisable. In the case of IFN-beta therapy for multiple sclerosis (MS), we obtained reproducible quantitative titers of NAbs using an improved and well-characterized assay based on a 10-fold reduction of a challenge dose of IFN-beta. However, the observed titer was significantly affected by the preparation of IFN-beta used as the assay challenge. NAb titers obtained using IFN-beta1b averaged 3-5-fold lower than titers of the same sample assayed using either IFN-beta1a or human fibroblast-derived IFN-beta. This was the case whether neutralizing serum was obtained from patients on therapy with IFN-beta1a or IFN-beta1b. The reason for this apparent titer difference is not fully understood but appears to be related to protein folding or other structural properties that differentiate the IFN-beta1b both from commercial IFN-beta1a preparations and from human fibroblast-derived IFN-beta.
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Trivalent influenza vaccine
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Abstract The latest SARS-CoV-2 variant of concern Omicron, with its immune escape from therapeutic anti-Spike monoclonal antibodies and WA-1 vaccine-elicited sera, demonstrates the continued relevance of COVID-19 convalescent plasma (CCP) therapies. Lessons learnt from previous usage of CCP suggests focusing on early outpatients and immunocompromised recipients, with high neutralizing antibody titer units. Here, we systematically review Omicron-neutralizing plasma activity data, and report that approximately 47% (424/902) of CCP samples from unvaccinated pre-Omicron donors neutralizes Omicron BA.1 with a very low geometric mean of geometric mean titers for 50% neutralization GM(GMT 50 ) of ~13, representing a > 20-fold reduction from WA-1 neutralization. Non-convalescent subjects who had received two doses of mRNA vaccines had a GM(GMT50) for Omicron BA.1 neutralization of ~27. However, plasma from vaccinees recovering from either previous pre-Omicron variants of concern infection, Omicron BA.1 infection, or third-dose uninfected vaccinees was nearly 100% neutralizing against Omicron BA.1, BA.2 and BA.4/5 with GM(GMT( 50 )) all over 189, 10 times higher than pre-Omicron CCP. Fully vaccinated and post-BA.1 plasma (Vax-CCP) had a GM(GMT 50 ) > 450 for BA.4/5 and >1,500 for BA.1 and BA.2. These findings have implications for both CCP stocks collected in prior pandemic periods and for future plans to restart CCP collections. Thus, Vax-CCP provides an effective tool to combat ongoing variants that escape therapeutic monoclonal antibodies.
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ABSTRACT To investigate the induction of neutralizing antibodies against Omicron after two and three vaccine doses in recipients of different ages. Physicians at Kobe University Hospital who had received the second dose of the BNT162b2 mRNA vaccine. At 2 months after the second vaccinations, the positive rate of neutralizing antibody against Omicron was 28%, and the titer was significantly lower than those against other variants, 11.8-fold and 3.6-fold lower than those against D614G and Delta, respectively. Unlike Delta, that positive rates of neutralizing antibody against Omicron were low in all age groups, and there was no significant difference in titers among age groups. Seven months after the 2nd dose, the positive rate of neutralizing antibody against Omicron decreased to 6%, but after the booster,3rd vaccination, it increased to 100%, and the titer was much higher than those at 2 and 7 months post-vaccination, 32-fold and 39-fold respectively. The booster vaccination effect was also observed in the younger at 41-fold, middle-aged at 43-fold, and older at 27-fold groups compared to the 7-month titers. Surprisingly, higher-than-predicted titers of the neutralizing antibodies against Omicron were induced after the booster vaccination regardless of recipient age, while this effect was not observed after two doses, indicating the induction of antibodies against common epitopes by the booster vaccination. Three doses can be confidently recommended to suppress the pandemic.
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Many variants of SARS-CoV-2 have emerged, and decreased neutralizing antibodies after vaccination and breakthrough infections have become a problem. The importance of monitoring titers of neutralizing antibodies is getting higher. We enrolled 146 COVID-19 patients, who were thought to be infected with Wuhan-hu-1 or D614G strains, and examined the time course of neutralizing titers against six concerning strains (Wuhan-hu-1, Alpha, Beta, Gamma, Kappa, and Delta) using newly developed ELISA. The acquisition of neutralizing titer was positively associated with disease severity. Immune evasions were observed approximately 20 to 30% for Alpha, Kappa, and Delta variant, and 40 to 45% for Beta and Gamma variant. The titers against all strains decreased over time, and interestingly, while titers against Wuhan-hu-1 decreased by 23%, those to Delta variant decreased by 70%. Our simple, cost-effective, and non-hazardous system will be applicable to process numerous samples, such as monitoring titers against prevalent strains after infection or vaccination.
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