Neutralization of VOCs including Delta one year post COVID-19 or vaccine

Background: SARS-CoV-2 variants, such as Alpha, Beta, Gamma and Delta, are raising concern about the efficiency of neutralizing antibodies (NAb) induced by wild-type infection or vaccines based on the wild-type spike. Methods: We determined IgG and NAb against SARS-CoV-2 variants one year following mild wild-type infection (n=104) and two-dose regimens with BNT162b2 (BNT/BNT) (n=67), ChAdOx1 (ChAd/ChAd) (n=82), or heterologous ChAdOx1 followed by BNT162b2 (ChAd/BNT) (n=116). Findings: Wild type spike IgG and NAb remained detectable in 80% (83/104) of unvaccinated participants one year post mild infection. The neutralizing capacity was similar against wild type (reference), Alpha (0.95 (0.92-0.98) and Delta 1.03 (0.95-1.11) but significantly reduced against Beta (0.54 (0.48-0.60)) and Gamma 0.51 (0.44-0.61). Similarly, BNT/BNT and ChAd/ChAd elicited sustained capacity against Alpha and Delta (1.01 (0.78-1.31) and 1.03 (0.95-1.11)) and (0.96 (0.84-1.09) and 0.82 (0.61-1.10) respectively), with reduced capacity against Beta (0.67 (0.50-0.88) and 0.53 (0.40-0.71)) and Gamma (0.12 (0.06-0.27) and 0.54 (0.37-0.80)). A similar trend was found following ChAd/BNT (0.74 (0.66-0.83) and 0.70 (0.50-0.97) against Alpha and Delta and 0.29 (0.20-0.42) and 0.13 (0.08-0.20) against Beta and Gamma). Interpretation: Persistent neutralization of the wide-spread Alpha and Delta variants one year after wild-type infection may aid vaccine policy makers in low-resource settings when prioritizing vaccine supply. The reduced capacity of neutralizing Beta and Gamma strains, but not the Alpha and Delta strains following both infection and three different vaccine regimens argues for caution against Beta and Gamma-exclusive mutations in the efforts to optimize next generation SARS-CoV-2 vaccines. Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section

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Four SARS-CoV-2 vaccines induce quantitatively different antibody responses against SARS-CoV-2 variants

10.1101/2021.09.27.21264163 ◽

2021 ◽

Author(s):

Marit J. van Gils ◽

Ayesha H.A. Lavell ◽

Karlijn van der Straten ◽

Brent Appelman ◽

Ilja Bontjer ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Adenovirus Vector ◽

Neutralizing Antibody ◽

Antibody Responses ◽

Wild Type ◽

Fold Reduction ◽

Antibody Titers ◽

Alpha Beta ◽

Vaccination Campaigns

Emerging and future SARS-CoV-2 variants may jeopardize the effectiveness of vaccination campaigns. We performed a head-to-head comparison of the ability of sera from individuals vaccinated with either one of four vaccines (BNT162b2, mRNA-1273, AZD1222 or Ad26.COV2.S) to recognize and neutralize the four SARS-CoV-2 variants of concern (VOCs; Alpha, Beta, Gamma and Delta). Four weeks after completing the vaccination series, SARS-CoV-2 wild-type neutralizing antibody titers were highest in recipients of BNT162b2 and mRNA-1273 (median titers of 1891 and 3061, respectively), and substantially lower in those vaccinated with the adenovirus vector-based vaccines AZD1222 and Ad26.COV2.S (median titers of 241 and 119, respectively). VOCs neutralization was reduced in all vaccine groups, with the largest (5.8-fold) reduction in neutralization being observed against the Beta variant. Overall, the mRNA vaccines appear superior to adenovirus vector-based vaccines in inducing neutralizing antibodies against VOCs four weeks after the final vaccination.

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Maintenance of neutralizing SARS-CoV-2 antibodies over five months in convalescent SARS-CoV-2 afflicted patients.

10.22541/au.160768745.52792441/v1 ◽

2020 ◽

Author(s):

Sissy Sonnleitner ◽

Martina Prelog ◽

Bainca Jansen ◽

Chantal Rodgarkia-Dara ◽

Sarah Gietl ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Primary Infection ◽

Protective Immunity ◽

Neutralization Assay ◽

Immunofluorescence Assay ◽

Crucial Importance ◽

Wild Type ◽

Specific Antibodies ◽

Chemiluminescent Immunoassay ◽

Type Infection

Level and duration of protective immunity against SARS-CoV-2 after primary infection is of crucial importance for preventive approaches. In order to provide evidence for the longevity of specific antibodies, we investigated the generation and maintenance of neutralizing antibodies of convalescent SARS-CoV-2-afflicted patients over a five month period post primary infection using an immunofluorescence assay, a commercial chemiluminescent immunoassay and an in-house enzyme-linked plaque-reduction neutralization assay. We present the successful application of an improved version of the plaque-reduction neutralization assay, which can be analyzed optometrically, significantly simplifying the interpretation of the results. Based on the results of the plaque-reduction neutralization assay, neutralizing antibodies were maintained in 85.3% of convalescent individuals without significant decay over five months. Furthermore, a positive correlation between severity of infection and neutralizing titer was shown. In conclusion, SARS-CoV-2-afflicted individuals have been proven to be able to establish and maintain neutralizing antibodies over a five months’ period after primary infection which allows to hope for long-lasting presumably protective humoral immunity after wild-type infection or even after vaccination.

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Neutralization of ancestral SARS-CoV-2 and variants Alpha, Beta, Gamma, Delta, Zeta and Omicron by mRNA vaccination and infection-derived immunity through homologous and heterologous variants

10.1101/2021.12.28.21268491 ◽

2021 ◽

Author(s):

Meriem Bekliz ◽

Kenneth Adea ◽

Pauline Vetter ◽

Christiane S Eberhardt ◽

Krisztina Hosszu-Fellous ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Immune Escape ◽

Neutralization Assay ◽

Significant Loss ◽

Antigenic Relationship ◽

Double Dose ◽

Gamma Delta ◽

Breakthrough Infection ◽

Neutralizing Capacity ◽

Alpha Beta

Emerging SARS-CoV-2 variants of concern/interest (VOC/VOI) raise questions about effectiveness of neutralizing antibodies derived from infection or vaccination. As the population immunity to SARS-CoV-2 has become more complex due to prior infection and/or vaccination, understanding the antigenic relationship between variants is needed. Here, we have assessed in total 104 blood specimens from convalescent individuals after infection with early-pandemic SARS-CoV-2 (pre-VOC) or with Alpha, Beta, Gamma or Delta, post-vaccination after double-dose mRNA-vaccination and break through infections due to Delta or Omicron. Neutralization against seven authentic SARS-CoV-2 isolates (B.1, Alpha, Beta, Gamma, Delta, Zeta, Omicron) was assessed by plaque-reduction neutralization assay. We found highest neutralization titers against the homologous (previously infecting) variant, with lower neutralization efficiency against heterologous variants. Significant loss of neutralization for Omicron was observed but to a varying degree depending on previously infecting variant (23.0-fold in Beta-convalescence up to 56.1-fold in Alpha-convalescence), suggesting that infection-derived immunity varies, but independent of the infecting variant is only poorly protective against Omicron. Of note, Zeta VOI showed also pronounced escape from neutralization of up to 28.2-fold in Alpha convalescent samples. Antigenic mapping reveals both Zeta and Omicron as separate antigenic clusters. Double dose vaccination showed robust neutralization for Alpha, Beta, Gamma, Delta and Zeta, with fold-change reduction of only 2.8 (for Alpha) up to 6.9 (for Beta). Escape from neutralization for Zeta was largely restored in vaccinated individuals, while Omicron still showed a loss of neutralization of 85.7-fold compared to pre-VOC SARS-CoV-2. Combined immunity from infection followed by vaccination or vaccine breakthrough infection showed highest titers and most robust neutralization for heterologous variants. Breakthrough infection with Delta showed only 12.5-fold reduced neutralization for Omicron, while breakthrough infection with Omicron showed only a 1.5-fold loss for Delta, suggests that infection with antigenically different variants can boost immunity for antigens closer to the vaccine strain. Antigenic cartography showed also a tendency towards broader neutralizing capacity for heterologous variants. We conclude that the complexity of background immunity needs to be taken into account when assessing new VOCs. Development towards separate serotypes such as Zeta was already observed before Omicron emergence, thus other factors than just immune escape must contribute to Omicrons rapid dominance. However, combined infection/vaccination immunity could ultimately lead to broad neutralizing capacity also against non-homologous variants.

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Determinants of early antibody responses to COVID-19 mRNA vaccines in exposed and naive healthcare workers

10.1101/2021.09.08.21263232 ◽

2021 ◽

Author(s):

Gemma Moncunill ◽

Ruth Aguilar ◽

Marta Ribes ◽

Natalia Ortega ◽

Rocío Rubio ◽

...

Keyword(s):

Health Care Workers ◽

Healthcare Workers ◽

Healthy Individuals ◽

Wild Type ◽

Post Vaccination ◽

Neutralization Capacity ◽

Care Workers ◽

Neutralizing Capacity ◽

One Year ◽

Antibody Levels

Background Two doses of mRNA vaccination have shown >94% efficacy at preventing COVID-19 mostly in naive adults, but it is not clear if the second dose is needed to maximize effectiveness in those previously exposed to SARS-CoV-2 and what other factors affect responsiveness. Methods We measured IgA, IgG and IgM levels against SARS-CoV-2 spike (S) and nucleocapsid (N) antigens from the wild-type and S from the Alpha, Beta and Gamma variants of concern, after BNT162b2 (Pfizer/BioNTech) or mRNA-1273 (Moderna) vaccination in a cohort of health care workers (N=578). Neutralizing capacity and antibody avidity were evaluated. Data were analyzed in relation to COVID-19 history, comorbidities, vaccine doses, brand and adverse events. Findings Vaccination induced robust IgA and IgG levels against all S antigens. Neutralization capacity and S IgA and IgG levels were higher in mRNA-1273 vaccinees, previously SARS-CoV-2 exposed, particularly if symptomatic, and in those experiencing systemic adverse effects. A second dose in pre-exposed did not increase antibody levels. Smoking and comorbidities were associated with lower neutralization and antibody levels. Among fully vaccinated, 6.3% breakthroughs were detected up to 189 days post-vaccination. Among pre-exposed non-vaccinated, 90% were IgG seropositive more than 300 days post-infection. Interpretation Our data support administering a single-dose in pre-exposed healthy individuals. However, heterogeneity of responses suggests that personalized recommendations may be necessary depending on COVID-19 history and life-style. Higher mRNA-1273 immunogenicity would be beneficial for those expected to respond worse to vaccination. Persistence of antibody levels in pre-exposed unvaccinated indicates maintenance of immunity up to one year.

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Study on Causes of Female Infertility at National Ayurveda Teaching Hospital, Borella, Sri Lanka: A Survey Based Study

Research in Pharmacy and Health Sciences ◽

10.32463/rphs.2017.v03i01.02 ◽

2017 ◽

Vol 3 (1) ◽

pp. 249-252

Author(s):

Farzana MUZN ◽

Arshiya Sultana

Keyword(s):

Sri Lanka ◽

Teaching Hospital ◽

Married Women ◽

Female Infertility ◽

Policy Makers ◽

Complex Disorder ◽

Anovulatory Cycle ◽

Common Causes ◽

Increasing Trend ◽

One Year

Background: Infertility is defined as the inability to conceive after at least one year of unprotected intercourse. It is a complex disorder with significant medical, psychosocial, and economic problems. In about one third of couples are infertile. Approximately 167 million married women aged 15-49 years in developing countries were infertility. The present study aimed to determine the most common causes of female infertility in patients who visiting the National Ayuvedic Teaching Hospital, Borella, Sri Lanka. Methods: In this study 635 infertile (primary and secondary) women were selected to determine the causes of infertility. The subjects were selected from the gynecology clinic, between the periods of February 2015 to March 2016. The data were gathered using a questionnaire; and after that proper statistical method was applied to analyze the data. Results: From the results age between 28-37 years (37.16%) are more prevalent to infertility and the causes of infertility are mainly due to anovulatory cycle (31.18%) and menstrual irregularities (19.21%). BMI also one of the significant cause for infertility. Conclusion: Therefore, identifying the risk factors and proper treatment on time along with policy makers providing facilities to resolve the infertility could possible diverse this alarming increasing trend of infertility.

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129 Genomic Relationship Between PRRSV Wild-type Infection and PRRSV Vaccination for Antibody Response and Reproductive Performance

Journal of Animal Science ◽

10.1093/jas/skab054.032 ◽

2021 ◽

Vol 99 (Supplement_1) ◽

pp. 18-18

Author(s):

Leticia P Sanglard ◽

Felipe Hickmann ◽

Yijian Huang ◽

Kent A Gray ◽

Daniel Linhares ◽

...

Keyword(s):

Antibody Response ◽

Reproductive Performance ◽

Genetic Correlations ◽

Clinical Signs ◽

Respiratory Syndrome Virus ◽

Wild Type ◽

Large White ◽

Selection For ◽

Indicator Trait ◽

Type Infection

Abstract Immunoglobulin G antibody response, measured as sample-to-positive (S/P) ratio, to Porcine Reproductive and Respiratory Syndrome virus (PRRSV) has been proposed as an indicator trait for improved reproductive performance in PRRSV-infected purebred sows and PRRSV-vaccinated crossbred gilts. In this study, we investigated the genetic correlations (rg) of S/P ratio following a PRRSV outbreak and PRRSV-vaccination with performance in non-exposed and PRRSV-exposed sows. PRRSV outbreak phase was defined based on previously described methodologies after the detection of typical clinical signs of PRRSV infection. 541 Landrace sows had S/P ratio measured at ~54 days after the beginning of the PRRSV outbreak (S/Poutbreak), and 906 Landrace x Large White naïve F1 gilts had S/P ratio measured at ~50 days after vaccination with a commercial modified live PRRSV vaccine (S/PVx). 711 and 428 Landrace sows had reproductive performance recorded before and during the PRRSV outbreak, respectively. 811 vaccinated F1 animals had farrowing performance for up to 3 parities. All animals were genotyped for ~28K SNPs. The estimate of rg of S/Poutbreakwith S/PVx was high (rg±SE = 0.72±0.18). Estimates of rg of S/Poutbreak with reproductive performance in F1 sows were low to moderate, ranging from 0.05±0.23 (number stillborn) to 0.30±0.20 (total number born). Estimates of rg of S/PVxwith reproductive performance in non-infected purebred sows were moderate and favorable with number born alive (0.50±0.23), but low (0 to -0.11±0.23) with litter mortality traits. Estimates of rg of S/PVx were moderate and negative (-0.47±0.18) with the number of mummies in PRRSV-infected purebred sows and low with other traits (-0.29±0.18 for total number born to 0.05±0.18 for number stillborn). These results indicate that selection for antibody response following a PRRSV outbreak collected in purebred sows and to PRRSV vaccination collected in commercial crossbred gilts may increase litter size of non-infected and PRRSV-exposed purebred and commercial crossbred sows.

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Protective efficacy of a SARS-CoV-2 DNA vaccine in wild-type and immunosuppressed Syrian hamsters

npj Vaccines ◽

10.1038/s41541-020-00279-z ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Rebecca L. Brocato ◽

Steven A. Kwilas ◽

Robert K. Kim ◽

Xiankun Zeng ◽

Lucia M. Principe ◽

...

Keyword(s):

Dna Vaccine ◽

Neutralizing Antibodies ◽

Protective Efficacy ◽

Phase 1 ◽

Severe Disease ◽

Disease Model ◽

Wild Type ◽

Jet Injection ◽

Syrian Hamsters ◽

Dna Targeting

AbstractA worldwide effort to counter the COVID-19 pandemic has resulted in hundreds of candidate vaccines moving through various stages of research and development, including several vaccines in phase 1, 2 and 3 clinical trials. A relatively small number of these vaccines have been evaluated in SARS-CoV-2 disease models, and fewer in a severe disease model. Here, a SARS-CoV-2 DNA targeting the spike protein and delivered by jet injection, nCoV-S(JET), elicited neutralizing antibodies in hamsters and was protective in both wild-type and transiently immunosuppressed hamster models. This study highlights the DNA vaccine, nCoV-S(JET), we developed has a great potential to move to next stage of preclinical studies, and it also demonstrates that the transiently-immunosuppressed Syrian hamsters, which recapitulate severe and prolonged COVID-19 disease, can be used for preclinical evaluation of the protective efficacy of spike-based COVID-19 vaccines.

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Despite vaccination, China needs non-pharmaceutical interventions to prevent widespread outbreaks of COVID-19 in 2021

Nature Human Behaviour ◽

10.1038/s41562-021-01155-z ◽

2021 ◽

Author(s):

Juan Yang ◽

Valentina Marziano ◽

Xiaowei Deng ◽

Giorgio Guzzetta ◽

Juanjuan Zhang ◽

...

Keyword(s):

Reproduction Number ◽

Synergetic Effect ◽

Data Driven ◽

Natural Immunity ◽

Epidemic Threshold ◽

Policy Makers ◽

Large Populations ◽

One Year ◽

Pharmaceutical Interventions

AbstractCOVID-19 vaccination is being conducted in over 200 countries and regions to control SARS-CoV-2 transmission and return to a pre-pandemic lifestyle. However, understanding when non-pharmaceutical interventions (NPIs) can be lifted as immunity builds up remains a key question for policy makers. To address this, we built a data-driven model of SARS-CoV-2 transmission for China. We estimated that, to prevent the escalation of local outbreaks to widespread epidemics, stringent NPIs need to remain in place at least one year after the start of vaccination. Should NPIs alone be capable of keeping the reproduction number (Rt) around 1.3, the synergetic effect of NPIs and vaccination could reduce the COVID-19 burden by up to 99% and bring Rt below the epidemic threshold in about 9 months. Maintaining strict NPIs throughout 2021 is of paramount importance to reduce COVID-19 burden while vaccines are distributed to the population, especially in large populations with little natural immunity.

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Kinetics of Neutralizing Antibodies of COVID-19 Patients Tested Using Clinical D614G, B.1.1.7 and B 1.351 Isolates in Microneutralization Assays

Viruses ◽

10.3390/v13060996 ◽

2021 ◽

Vol 13 (6) ◽

pp. 996

Author(s):

Jenni Virtanen ◽

Ruut Uusitalo ◽

Essi M. Korhonen ◽

Kirsi Aaltonen ◽

Teemu Smura ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Acute Infection ◽

Clinical Isolates ◽

Wild Type Virus ◽

Type Virus ◽

Wild Type ◽

Kinetics Of

Increasing evidence suggests that some newly emerged SARS-CoV-2 variants of concern (VoCs) resist neutralization by antibodies elicited by the early-pandemic wild-type virus. We applied neutralization tests to paired recoveree sera (n = 38) using clinical isolates representing the first wave (D614G), VoC1, and VoC2 lineages (B.1.1.7 and B 1.351). Neutralizing antibodies inhibited contemporary and VoC1 lineages, whereas inhibition of VoC2 was reduced 8-fold, with 50% of sera failing to show neutralization. These results provide evidence for the increased potential of VoC2 to reinfect previously SARS-CoV-infected individuals. The kinetics of NAbs in different patients showed similar decline against all variants, with generally low initial anti-B.1.351 responses becoming undetectable, but with anti-B.1.1.7 NAbs remaining detectable (>20) for months after acute infection.

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Neutralizing Antibodies Titers and Side Effects in Response to BNT162b2 Vaccine in Healthcare Workers with and without Prior SARS-CoV-2 Infection

Vaccines ◽

10.3390/vaccines9070742 ◽

2021 ◽

Vol 9 (7) ◽

pp. 742

Author(s):

José Javier Morales-Núñez ◽

José Francisco Muñoz-Valle ◽

Carlos Meza-López ◽

Lin-Fa Wang ◽

Andrea Carolina Machado Sulbarán ◽

...

Keyword(s):

Single Dose ◽

Side Effects ◽

Adverse Effects ◽

Antibody Production ◽

Neutralizing Antibodies ◽

Healthcare Workers ◽

Vaccination Program ◽

Expected Result ◽

Neutralizing Capacity ◽

The Usa

The main expected result of a vaccine against viruses is the ability to produce neutralizing antibodies. Currently, several vaccines against SARS-CoV-2 are being applied to prevent mortal complications, being Pfizer-BioNTech (BNT162b2) one of the first to be authorized in the USA and Mexico (11 December 2020). This study evaluated the efficacy of this vaccine on antibody production with neutralizing capacity and its side effects in healthcare workers with and without prior SARS-CoV-2 infection and in a group of unvaccinated individuals with prior COVID-19. The main findings are the production of 100% neutralizing antibodies in both groups after the second dose, well-tolerated adverse effects, the possible presence of immunosenescence, and finally, we support that a single dose of this vaccine in individuals with prior COVID-19 would be sufficient to achieve an immunization comparable to people without prior COVID-19 with a complete vaccination program (2 doses).

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