BREAKING! Australian Study Warns That Antibodies Produced In Individuals Infected With Earlier Strains Not Effective Against Emerging Variants

COVID-19 Immunology: Australian scientists from the University of New South Wales, the Children’s Hospital at Westmead-Sydney, Westmead Institute for Medical Research-Sydney and the New South Wales Health Pathology-Sydney researching how our immune system responds to COVID-19 have discovered  that those infected by early SARS-CoV-2 strains in 2020 produced sustained antibodies, however, these antibodies are not as effective against contemporary variants of the virus.

The SARS-CoV-2 antibody neutralization response and its evasion by emerging viral variants and variant of concern (VOC) are unknown, but critical to understand reinfection risk and breakthrough infection following vaccination.
 
Antibody immunoreactivity against SARS-CoV-2 antigens and Spike variants, inhibition of Spike-driven virus–cell fusion, and infectious SARS-CoV-2 neutralization were characterized in 807 serial samples from 233 reverse transcription polymerase chain reaction (RT-PCR)–confirmed COVID-19 diseased individuals with detailed demographics and followed up to 7 months.
 
A broad and sustained polyantigenic immunoreactivity against SARS-CoV-2 Spike, Membrane, and Nucleocapsid proteins, along with high viral neutralization, was associated with COVID-19 severity. A subgroup of “high responders” maintained high neutralizing responses over time, representing ideal convalescent plasma donors.
 
The study findings showed that antibodies generated against SARS-CoV-2 during the first COVID-19 wave had reduced immunoreactivity and neutralization potency to emerging Spike variants and VOC. Accurate monitoring of SARS-CoV-2 antibody responses would be essential for selection of optimal responders and vaccine monitoring and design.
 
The study findings were published in the peer reviewed journal: PLOS Medicine. https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1003656
 
 
This study can be considered as one of the world's most comprehensive studies of the immune response against COVID-19 infection.
 
The study also shows the need to invest in new vaccine designs to keep pace with emerging COVID variants.
 
The study team analyzed the serum of 233 individuals diagnosed with COVID-19 over 7 months and uncovered that the level of immunity over time is dependent on disease severity and the viral variant.
 
The team show that antibodies developed during the first wave had reduced effectiveness against six variants, ranging from those observed in the second wave in Australia through to three variants of concern that have driven the global pandemic in the UK, Brazil and South Africa.
 
According to the study team, the serum of COVID-19 infected individuals was of interest as it is the part of our blood that contains crucial information about our immune system. Analysis of the serum made it possible to create a detailed timeline of the level of 'neutralizing antibodies' produced against COVID-19 infection, and so to see if there was long-term immunity.
 
The neutralizing antibodies are part of our immune system's frontline arsenal that is triggered during infection and vaccination. Their job is to shield cells that are usually the target of a pathogen (such as the SARS-CoV-2 virus which causes the COVID-19 disease) from being infected. The level of neutralizing antibody response can be a defining feature of how effectively our body fights off illness.
 
In the study a rare group of 'super responders' was also identified as an exception.
 
Interestingly this group of 'super responders' had a stable and robust level of antibodies across all COVID-19 variants.
 
The study team says this group could prove useful for investigating the potential of convalescent plasma (using blood from people who have recovered to treat others) which has so far proven ineffective against severe COVID-19 illness. In addition, key donors could be looked at closely and their antibodies cloned for future therapeutic use.
 
Associate Professor Fabienne Brilot of the University of Sydney and Kids Research, Sydney Children's Hospitals Network who was also the co-senior author led the analysis branch of the study, using highly sensitive tools they developed to study the antibodies in detail.
 
According to the researchers, we can learn a great deal from these people who were infected in the first wave in Australia as they were infected with the same variant that our current vaccines are based on. The study highlights the importance of continued vaccine development, especially taking into account the differences in variants.
 
Associate Professor Dr Stuart Turville from the Kirby Institute at the University of New South Wales said that the study was conducted to investigate the level, breadth and longevity of the immunity generated from COVID-19 infection and whether mutation of the virus compromises immunity.
 
Dr Turville added, "What this work has shown us is that current observations about vaccines show they offer a much broader protection against COVID-19 and its variants than the body's natural immune response following infection, which is usually only protective against the variant of the virus that the person was infected with. We, therefore, should not rely on the body's natural immune response to control this pandemic, but rather the broadly protective vaccines that are available."
 
The study key findings were:
 
-1) SARS-CoV-2 antibody responses are sustained for up to seven months post-infection.
 
-2) The immune response remained stable in some individuals, and while it decreased in others, no individual showed a negative response during the seven-month period.
 
-3 )Levels of virus-neutralizing antibodies were associated with COVID-19 severity.
 
-4 )Antibodies generated after early infection displayed a significantly reduced antibody binding and neutralization potency to globally emerging viral variants.
Methods
 
The researchers analyzed the serum from 233 individuals who were diagnosed with COVID-19 from February to October 2020. There were two cohorts to the study--a hospital-based cohort of patients (the ADAPT study at St Vincent's Hospital, Sydney) recruited during the first and second wave of infection in Australia and a national cohort of plasma donors (LIFEBLOOD).
 
In all, 10 COVID-19 strains and variants of concern/ interest were investigated, including: the First known classified SARS-CoV-2 strain (Wuhan -1 D614), Alpha (B.1.1.7, United Kingdom), Beta (B.1.351, South Africa), Gamma (P1, Brazilian)
And Zeta (P2, Brazilian).
 
The study team used a comprehensive suite of assays that measured:

-a) The longevity and type of antibody response against Spike from various variants over time in serum of COVID-19 diagnosed individuals.

-b) Neutralization of infectious SARS-CoV-2 over time, by infecting cell lines that had ACE2 on its surface (which SARS-CoV-2 binds and targets on the cell to begin infection) with a particle designed to mimic a version of the SARS-CoV-2 virus particle.
 
The study team concluded, “Our study findings readily imply a need for periodic updates in vaccine design, as for the influenza vaccine. It is highly probable that we will need to address future VOC that provide even greater challenges for current vaccine design, additional spike changes, such as Q498R and/or the merging of S477N with E484K and N501Y, which can lead to further fitness gains. For instance, a Spike RBD with S477N, E484K, Q498K, and N501Y produces a SARS RBD that is 600-fold greater at engaging ACE2. In that context, how such a SARS-CoV-2 infection would proceed and whether current vaccines would provide sufficient protection is presently unknown. Our evidence that S477N/D614G-infected patients have a similar binding to this variant, albeit reduced, compared to first wave patients, may suggest changing the Wuhan-1 D614 Spike to the S477N/D614G variant in vaccine generation may not overcome the resistance of this variant to the neutralizing antibody response. As antibodies against Spike harness the majority of neutralizing activity, selecting the optimal Spike variants in monovalent or multivalent vaccine strategies may be critical.”
 
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