Efficacy and breadth of adjuvanted SARS-CoV-2 receptor-binding domain nanoparticle vaccine in macaques
Hannah A. D. KingMichael JoyceInès Lakhal-NaouarAslaa AhmedCamila Macedo CincottaCaroline SubraKristina K. PeachmanHolly R. HackRita E. ChenPaul V. ThomasWei‐Hung ChenRajeshwer S. SankhalaAgnes HajduczkiElizabeth J. MartinezCaroline E. PetersonWilliam C. ChangMisook ChoeClayton SmithJarrett A. HeadleyHanne Andersen ElyardAnthony CookAlexander AndersonKathryn McGuckin WuertzMing DongIsabella SwaffordJames Brett CaseJeffrey R. CurrierKerri G. LalMihret F. AmareVincent DussuptSebastian MolnarSharon P. DayeXiankun ZengErica K. BarkeiKendra J. AlfsonHilary StaplesRicardo CarrionShelly J. KrebsDominic Paquin‐ProulxNicos KarasavvasVictoria R. PolonisLinda L. JagodzinskiSandhya VasanPaul T. ScottYaoxing HuangManoj S. NairDavid D. HoNatalia de ValMichael DiamondMark G. LewisMangala RaoGary R. MatyasGregory D. GromowskiSheila A. PeelNelson L. MichaelKayvon ModjarradDiane L. Bolton
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Abstract:
Emergence of novel variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need for next-generation vaccines able to elicit broad and durable immunity. Here we report the evaluation of a ferritin nanoparticle vaccine displaying the receptor-binding domain of the SARS-CoV-2 spike protein (RFN) adjuvanted with Army Liposomal Formulation QS-21 (ALFQ). RFN vaccination of macaques using a two-dose regimen resulted in robust, predominantly Th1 CD4+ T cell responses and reciprocal peak mean serum neutralizing antibody titers of 14,000 to 21,000. Rapid control of viral replication was achieved in the upper and lower airways of animals after high-dose SARS-CoV-2 respiratory challenge, with undetectable replication within 4 d in seven of eight animals receiving 50 µg of RFN. Cross-neutralization activity against SARS-CoV-2 variant B.1.351 decreased only approximately twofold relative to WA1/2020. In addition, neutralizing, effector antibody and cellular responses targeted the heterotypic SARS-CoV-1, highlighting the broad immunogenicity of RFN-ALFQ for SARS-CoV-like Sarbecovirus vaccine development.Keywords:
Coronavirus
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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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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Abstract Objectives To assess the neutralization activity pre and post Omicron BA.1 emergence in a unique cohort of 280 vaccinated restaurant/bar, grocery and hardware store workers in Québec, Canada. Methods Participants were recruited during the emergence of Omicron BA.1 variant. The neutralizing activity of participant sera was assessed by microneutralization assay. Results Serum neutralizing antibody (NtAb) titers of all participants against the ancestral SARS-CoV-2 strain was comparable with the response against Delta variant, however, their response was significantly reduced against Omicron BA.1, BA2, BA.2.12.1, BA.4 and BA.5. The neutralizing response of each group of workers was similar. Individuals who received 2 doses of vaccine had significantly reduced NtAb titers against all SARS-CoV-2 strains compared to those infected and then vaccinated (≥1 dose), vaccinated (≥2 doses) and then infected, or those who received 3 doses of vaccine. Participants vaccinated with 2 or 3 doses of vaccine and then infected had the highest NtAb titers against all SARS-CoV-2 strains tested. Conclusion We assessed for the first time the NtAb response in food and retail workers. Individuals infected after ≥2 doses of vaccine had the highest levels of NtAbs against Omicron BA.1, BA.2 and BA.5 variants and might be better protected against reinfection.
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Summary Studies have been reported which led to the development of a reliable and reproducible neutralization test for mumps in the chick embryo, employing serial dilutions of inactivated serum and constant amounts of virus. Slight variations in the concentration of test agent fail to influence significantly the results in that a 1000-fold increase in mumps virus reduces the serum titer by only 10-fold. Convalescent sera showed a wide variation in neutralizing titers, ranging from 1:8 to greater than 1:2000. Analysis of serial sera from individual patients revealed that maximal levels were ordinarily attained within 3 weeks, and remained at this level for several months before a gradual decline was detected. Subclinical cases exhibited similar titers. Exceptional patients may develop only low levels of neutralizing antibodies. A comparison of neutralizing, complement-fixing (V and S antigens) and hemagglutination inhibiting titers failed to reveal correlations. The ratios of neutralizing and complement fixing titers varied over a 1000-fold range, those of neutralizing and hemagglutination inhibiting titers over a 40-fold range. These variations were of an order far greater than could be accounted for on technical grounds and the suggestion has been offered that the various technics measure different antibodies. The fact that one or the other antibody may fail to appear in the serum of convalescents from mumps, offers a practical diagnostic problem which has been discussed.
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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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Porcine epidemic diarrhea (PED) is a highly contagious disease that causes high mortality in suckling piglets. Although several licensed inactivated and live attenuated vaccines were widely used, the infection rate remains high due to unsatisfactory protective efficacy. In this study, mRNA vaccine candidates against PED were prepared, and their immunogenicity was evaluated in mice and pregnant sows. The mRNA PED vaccine based on heterodimer of viral receptor binding region (RBD) showed good immunogenicity. It elicited robust humoral and cellular immune responses in mice, and the neutralizing antibody titer reached 1:300 after a single vaccination. Furthermore, it induced neutralizing antibody level similar to that of the inactivated vaccine in pregnant sows. This study developed a new design of PED vaccine based on the mRNA-RBD strategy and demonstrated the potential for clinical application.
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