scholarly journals Reduced neutralisation of the Delta (B.1.617.2) SARS-CoV-2 variant of concern following vaccination

2021 ◽  
Vol 17 (12) ◽  
pp. e1010022
Author(s):  
Chris Davis ◽  
Nicola Logan ◽  
Grace Tyson ◽  
Richard Orton ◽  
William T. Harvey ◽  
...  
Keyword(s):  
South African ◽  
Vaccine Efficacy ◽  
Antigenic Drift ◽  
Productive Infection ◽  
Subsequent Reduction ◽  
Fold Reduction ◽  
Antibody Titres ◽  
Efficacy Assessment ◽  
Induced Immunity ◽  
Over Time

Vaccines are proving to be highly effective in controlling hospitalisation and deaths associated with SARS-CoV-2 infection but the emergence of viral variants with novel antigenic profiles threatens to diminish their efficacy. Assessment of the ability of sera from vaccine recipients to neutralise SARS-CoV-2 variants will inform the success of strategies for minimising COVID19 cases and the design of effective antigenic formulations. Here, we examine the sensitivity of variants of concern (VOCs) representative of the B.1.617.1 and B.1.617.2 (first associated with infections in India) and B.1.351 (first associated with infection in South Africa) lineages of SARS-CoV-2 to neutralisation by sera from individuals vaccinated with the BNT162b2 (Pfizer/BioNTech) and ChAdOx1 (Oxford/AstraZeneca) vaccines. Across all vaccinated individuals, the spike glycoproteins from B.1.617.1 and B.1.617.2 conferred reductions in neutralisation of 4.31 and 5.11-fold respectively. The reduction seen with the B.1.617.2 lineage approached that conferred by the glycoprotein from B.1.351 (South African) variant (6.29-fold reduction) that is known to be associated with reduced vaccine efficacy. Neutralising antibody titres elicited by vaccination with two doses of BNT162b2 were significantly higher than those elicited by vaccination with two doses of ChAdOx1. Fold decreases in the magnitude of neutralisation titre following two doses of BNT162b2, conferred reductions in titre of 7.77, 11.30 and 9.56-fold respectively to B.1.617.1, B.1.617.2 and B.1.351 pseudoviruses, the reduction in neutralisation of the delta variant B.1.617.2 surpassing that of B.1.351. Fold changes in those vaccinated with two doses of ChAdOx1 were 0.69, 4.01 and 1.48 respectively. The accumulation of mutations in these VOCs, and others, demonstrate the quantifiable risk of antigenic drift and subsequent reduction in vaccine efficacy. Accordingly, booster vaccines based on updated variants are likely to be required over time to prevent productive infection. This study also suggests that two dose regimes of vaccine are required for maximal BNT162b2 and ChAdOx1-induced immunity.

scholarly journals Reduced neutralisation of the Delta (B.1.617.2) SARS-CoV-2 variant of concern following vaccination

2021 ◽  
Author(s):  
Chris Davis ◽  
Nicola Logan ◽  
Grace Tyson ◽  
Richard Orton ◽  
William Harvey ◽  
...  
Keyword(s):  
South African ◽  
Vaccine Efficacy ◽  
Antigenic Drift ◽  
Productive Infection ◽  
Subsequent Reduction ◽  
Fold Reduction ◽  
Antibody Titres ◽  
Efficacy Assessment ◽  
Induced Immunity ◽  
Over Time

Vaccines are proving to be highly effective in controlling hospitalisation and deaths associated with SARS-CoV-2 infection but the emergence of viral variants with novel antigenic profiles threatens to diminish their efficacy. Assessment of the ability of sera from vaccine recipients to neutralise SARS-CoV-2 variants will inform the success of strategies for minimising COVID19 cases and the design of effective antigenic formulations. Here, we examine the sensitivity of variants of concern (VOCs) representative of the B.1.617.1 and B.1.617.2 (first associated with infections in India) and B.1.351 (first associated with infection in South Africa) lineages of SARS-CoV-2 to neutralisation by sera from individuals vaccinated with the BNT162b2 (Pfizer/BioNTech) and ChAdOx1 (Oxford/AstraZeneca) vaccines. Across all vaccinated individuals, the spike glycoproteins from B.1.617.1 and B.1.617.2 conferred reductions in neutralisation of 4.31 and 5.11-fold respectively. The reduction seen with the B.1.617.2 lineage approached that conferred by the glycoprotein from B.1.351 (South African) variant (6.29-fold reduction) that is known to be associated with reduced vaccine efficacy. Neutralising antibody titres elicited by vaccination with two doses of BNT162b2 were significantly higher than those elicited by vaccination with two doses of ChAdOx1. Fold decreases in the magnitude of neutralisation titre following two doses of BNT162b2, conferred reductions in titre of 7.77, 11.30 and 9.56-fold respectively to B.1.617.1, B.1.617.2 and B.1.351 pseudoviruses, the reduction in neutralisation of the delta variant B.1.617.2 surpassing that of B.1.1351. Fold changes in those vaccinated with two doses of ChAdOx1 were 0.69, 4.01 and 1.48 respectively. The accumulation of mutations in these VOCs, and others, demonstrate the quantifiable risk of antigenic drift and subsequent reduction in vaccine efficacy. Accordingly, booster vaccines based on updated variants are likely to be required over time to prevent productive infection. This study also suggests that two dose regimes of vaccine are required for maximal BNT162b2 and ChAdOx1-induced immunity.

scholarly journals SARS-CoV-2 Omicron Spike recognition by plasma from individuals receiving BNT162b2 mRNA vaccination with a 16-weeks interval between doses

2021 ◽  
Author(s):  
Debashree Chatterjee ◽  
Alexandra Tauzin ◽  
Lorie Marchitto ◽  
Shang Yu Gong ◽  
Marianne Boutin ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Vaccine Efficacy ◽  
Short Interval ◽  
Antigenic Drift ◽  
Alpha Beta ◽  
Induced Immunity ◽  
Plasma Activity

Continuous emergence of SARS-CoV-2 variants of concern (VOC) is fueling the COVID-19 pandemic. Omicron (B.1.1.529), is rapidly spreading worldwide. The large number of mutations in its Spike raised concerns about a major antigenic drift that could significantly decrease vaccine efficacy and infection-induced immunity. A long interval between BNT162b2 mRNA doses was shown to elicit antibodies that efficiently recognize Spikes from different VOCs. Here we evaluated the recognition of Omicron Spike by plasma from a cohort of SARS-CoV-2 naive and previously-infected individuals that received their BNT162b2 mRNA vaccine 16-weeks apart. Omicron Spike was recognized less efficiently than D614G, Alpha, Beta, Gamma and Delta Spikes. We compared to plasma activity from participants receiving a short (4-weeks) interval regimen. Plasma from individuals of the long interval cohort neutralized better the Omicron Spike compared to those that received a short interval. Whether this difference confers any clinical benefit against Omicron remains unknown.

scholarly journals Host Factors Impact Vaccine Efficacy: Implications for Seasonal and Universal Influenza Vaccine Programs

2019 ◽  
Vol 93 (21) ◽  
Author(s):  
Santosh Dhakal ◽  
Sabra L. Klein
Keyword(s):  
Influenza Virus ◽  
Influenza Vaccine ◽  
Virus Vaccine ◽  
Vaccine Efficacy ◽  
Public Health Problem ◽  
Influenza Virus Vaccine ◽  
Host Factors ◽  
Influenza Vaccines ◽  
Vaccine Type ◽  
Induced Immunity

ABSTRACT Influenza is a global public health problem. Current seasonal influenza vaccines have highly variable efficacy, and thus attempts to develop broadly protective universal influenza vaccines with durable protection are under way. While much attention is given to the virus-related factors contributing to inconsistent vaccine responses, host-associated factors are often neglected. Growing evidences suggest that host factors including age, biological sex, pregnancy, and immune history play important roles as modifiers of influenza virus vaccine efficacy. We hypothesize that host genetics, the hormonal milieu, and gut microbiota contribute to host-related differences in influenza virus vaccine efficacy. This review highlights the current insights and future perspectives into host-specific factors that impact influenza vaccine-induced immunity and protection. Consideration of the host factors that affect influenza vaccine-induced immunity might improve influenza vaccines by providing empirical evidence for optimizing or even personalizing vaccine type, dose, and use of adjuvants for current seasonal and future universal influenza vaccines.

scholarly journals Chimeric spike mRNA vaccines protect against sarbecovirus challenge in mice

2021 ◽  
Author(s):  
David R. Martinez ◽  
Alexandra Schaefer ◽  
Sarah R. Leist ◽  
Gabriela De la Cruz ◽  
Ande West ◽  
...  
Keyword(s):  
South African ◽  
Neutralizing Antibodies ◽  
Lung Pathology ◽  
Breakthrough Infection ◽  
Neutralization Activity ◽  
Vaccination Strategies ◽  
Binding Domains ◽  
Limited Efficacy ◽  
Fold Reduction ◽  
Novel Strategy

AbstractThe emergence of SARS-CoV and SARS-CoV-2 in the 21st century highlights the need to develop universal vaccination strategies against the SARS-related Sarbecovirus subgenus. Using structure-guided chimeric spike designs and multiplexed immunizations, we demonstrate protection against SARS-CoV, SARS-CoV-2, and bat CoV (BtCoV) RsSHC014 challenge in highly vulnerable aged mice. Chimeric spike mRNAs containing N-terminal domain (NTD), and receptor binding domains (RBD) induced high levels of broadly protective neutralizing antibodies against three high-risk sarbecoviruses: SARS-CoV, RsSHC014, and WIV-1. In contrast, SARS-CoV-2 mRNA vaccination not only showed a 10 to >500-fold reduction in neutralizing titers against heterologous sarbecovirus strains, but SARS-CoV challenge in mice resulted in breakthrough infection including measurable lung pathology. Importantly, chimeric spike mRNA vaccines efficiently neutralized both the D614G and the South African B.1.351 variants of concern despite some reduction in neutralization activity. Thus, multiplexed-chimeric spikes may provide a novel strategy to prevent pandemic and SARS-like zoonotic coronavirus infections, while revealing the limited efficacy of SARS-CoV-2 spike vaccines against other sarbecoviruses.

scholarly journals ChAdOx1 nCoV-19 (AZD1222) protects Syrian hamsters against SARS-CoV-2 B.1.351 and B.1.1.7

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Robert J. Fischer ◽  
Neeltje van Doremalen ◽  
Danielle R. Adney ◽  
Claude Kwe Yinda ◽  
Julia R. Port ◽  
...  
Keyword(s):  
Single Dose ◽  
Vaccine Efficacy ◽  
Infectious Virus ◽  
Neutralizing Antibody ◽  
Subgenomic Rna ◽  
Syrian Hamsters ◽  
Fold Reduction ◽  
Histopathological Evaluation ◽  
Gross Lesions ◽  
Pulmonary Pathology

AbstractWe investigated ChAdOx1 nCoV-19 (AZD1222) vaccine efficacy against SARS-CoV-2 variants of concern (VOCs) B.1.1.7 and B.1.351 in Syrian hamsters. We previously showed protection against SARS-CoV-2 disease and pneumonia in hamsters vaccinated with a single dose of ChAdOx1 nCoV-19. Here, we observe a 9.5-fold reduction of virus neutralizing antibody titer in vaccinated hamster sera against B.1.351 compared to B.1.1.7. Vaccinated hamsters challenged with B.1.1.7 or B.1.351 do not lose weight compared to control animals. In contrast to control animals, the lungs of vaccinated animals do not show any gross lesions. Minimal to no viral subgenomic RNA (sgRNA) and no infectious virus can be detected in lungs of vaccinated animals. Histopathological evaluation shows extensive pulmonary pathology caused by B.1.1.7 or B.1.351 replication in the control animals, but none in the vaccinated animals. These data demonstrate the effectiveness of the ChAdOx1 nCoV-19 vaccine against clinical disease caused by B.1.1.7 or B.1.351 VOCs.

scholarly journals Rapid and Successful Implementation of a COVID-19 Convalescent Plasma Programme—The South African Experience

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2050
Author(s):  
Tanya Nadia Glatt ◽  
Caroline Hilton ◽  
Cynthia Nyoni ◽  
Avril Swarts ◽  
Ronel Swanevelder ◽  
...  
Keyword(s):  
South Africa ◽  
South African ◽  
Successful Implementation ◽  
Western Cape ◽  
The South ◽  
South Africans ◽  
African Experience ◽  
Antibody Titres ◽  
Investigational Therapies ◽  
Set Up

Background: COVID-19 convalescent plasma (CCP) has been considered internationally as a treatment option for COVID-19. CCP refers to plasma collected from donors who have recovered from and made antibodies to SARS-CoV-2. To date, convalescent plasma has not been collected in South Africa. As other investigational therapies and vaccination were not widely accessible, there was an urgent need to implement a CCP manufacture programme to service South Africans. Methods: The South African National Blood Service and the Western Cape Blood Service implemented a CCP programme that included CCP collection, processing, testing and storage. CCP units were tested for SARS-CoV-2 Spike ELISA and neutralising antibodies and routine blood transfusion parameters. CCP units from previously pregnant females were tested for anti-HLA and anti-HNA antibodies. Results: A total of 987 CCP units were collected from 243 donors, with a median of three donations per donor. Half of the CCP units had neutralising antibody titres of >1:160. One CCP unit was positive on the TPHA serology. All CCP units tested for anti-HLA antibodies were positive. Conclusion: Within three months of the first COVID-19 diagnosis in South Africa, a fully operational CCP programme was set up across South Africa. The infrastructure and skills implemented will likely benefit South Africans in this and future pandemics.

scholarly journals SARS-CoV-2 Convalescent Sera Binding and Neutralizing Antibody Concentrations Compared with COVID-19 Vaccine Efficacy Estimates Against Symptomatic Infection

2021 ◽  
Author(s):  
Amy J. Schuh ◽  
Panayampalli S. Satheshkumar ◽  
Stephanie Dietz ◽  
Lara Bull-Otterson ◽  
Myrna Charles ◽  
...  
Keyword(s):  
Vaccine Efficacy ◽  
Neutralizing Antibody ◽  
Published Data ◽  
Symptomatic Infection ◽  
Convenience Sample ◽  
Post Vaccination ◽  
Antibody Assays ◽  
Study Population ◽  
Binding Antibody ◽  
Induced Immunity

Previous vaccine efficacy (VE) studies have estimated neutralizing and binding antibody concentrations that correlate with protection from symptomatic infection; how these estimates compare to those generated in response to SARS-CoV-2 infection is unclear. Here, we assessed quantitative neutralizing and binding antibody concentrations using standardized SARS-CoV-2 assays on 3,067 serum specimens collected during July 27, 2020-August 27, 2020 from COVID-19 unvaccinated persons with detectable anti-SARS-CoV-2 antibodies using qualitative antibody assays. Quantitative neutralizing and binding antibody concentrations were strongly positively correlated (r=0.76, p<0.0001) and were noted to be several fold lower in the unvaccinated study population as compared to published data on concentrations noted 28 days post-vaccination. In this convenience sample, ~88% of neutralizing and ~63-86% of binding antibody concentrations met or exceeded concentrations associated with 70% COVID-19 VE against symptomatic infection from published VE studies; ~30% of neutralizing and 1-14% of binding antibody concentrations met or exceeded concentrations associated with 90% COVID-19 VE. These data support observations of infection-induced immunity and current recommendations for vaccination post infection to maximize protection against symptomatic COVID-19.

scholarly journals Private hospital expenditure and relation to utilisation: Observations from the data

2018 ◽  
Vol 21 (1) ◽  
Author(s):  
Marine Erasmus ◽  
Helen Kean
Keyword(s):  
South Africa ◽  
Older People ◽  
South African ◽  
Market Share ◽  
Private Hospital ◽  
Private Hospitals ◽  
Detailed Understanding ◽  
Hospital Market ◽  
Hospital Expenditure ◽  
Over Time

Background: This study contributes to the detailed understanding of the drivers of medical scheme expenditure on private hospitals in South Africa over 2006–2014. This is important in the context of various regulatory reforms that are being considered at present. Aim: The aim is to provide an updated analysis and description of the drivers of medical scheme expenditure on private hospitals in South Africa. Setting: Private hospital market, South Africa. Methods: Data from the three largest private hospital groups – which account for approximately 70% of the South African private hospital market share – are collected, aggregated and analysed. This study uses targeted descriptive and exploratory analyses, relying on a residual approach to hospital expenditure. Results: It is found that over time medical scheme beneficiaries, on average, are being admitted to private hospitals more frequently, as well as staying in hospital for longer during each admission. The data also indicate that over time older people are being admitted to hospital more often. Conclusion: This study’s findings contradict previous assertions that it is only prices driving increased medical scheme expenditure on private hospitals.

The Earliest South African Hominids

2021 ◽  
Vol 50 (1) ◽  
pp. 125-143
Author(s):  
Ronald J. Clarke ◽  
Travis Rayne Pickering ◽  
Jason L. Heaton ◽  
Kathleen Kuman
Keyword(s):  
East Africa ◽  
South African ◽  
The South ◽  
Taxonomic Assignment ◽  
First Time ◽  
Over Time

The earliest South African hominids (humans and their ancestral kin) belong to the genera Australopithecus, Paranthropus, and Homo, with the oldest being a ca. 3.67 million-year-old nearly complete skeleton of Australopithecus (StW 573) from Sterkfontein Caves. This skeleton has provided, for the first time in almost a century of research, the full anatomy of an Australopithecus individual with indisputably associated skull and postcranial bones that give complete limb lengths. The three genera are also found in East Africa, but scholars have disagreed on the taxonomic assignment for some fossils owing to historical preconceptions. Here we focus on the South African representatives to help clarify these debates. The uncovering of the StW 573 skeleton in situ revealed significant clues concerning events that had affected it over time and demonstrated that the associated stalagmite flowstones cannot provide direct dating of the fossil, as they are infillings of voids caused by postdepositional collapse.

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