Evolution of SARS-CoV-2 has led to the more infectious Delta variant. By mid-August, 2021, Delta has risen to 86% of sequenced SARS-CoV-2 viral samples in the USA. Which is remarkable because as recent as May 15th, 2021 Delta only represented 2% of sequenced samples.
Despite vaccines that induce a strong antibody response against the original, wild type (WT) virus, Delta variant is causing breakthrough infections.
To better understand how antibodies produced after vaccination or natural infection protect against the Delta variant, we ran serum samples from 49 individuals with Genscript's cPASS neutralizing antibody platform.
Delta variant had lower average neutralization values than WT for all cohorts (Figure 1). No cohort dropped from a positive composite value to negative. The J&J vaccine cohort had the lowest Delta neutralization at 33%. The largest difference between WT and Delta variant neutralization was the Natural Infection group, who's average neutralization dropped 17% against Delta. The Pfizer and Moderna vaccine cohorts had a 6% and 8% reduction with Delta, respectively.
Most individual samples showed reduced neutralization against Delta compared to WT. One individual (CH-AS00086) who recovered from natural infection had higher neutralization against Delta than WT. Their infection onset was July 21, 2021, which is in alignment with Delta variant's abundance in the US population.
The individual with the J&J vaccine followed by breakthrough infection had WT and Delta neutralization >96%. This is more than double the average neutralization for the J&J alone cohort (Figure 2).
Pfizer and Moderna vaccine cohorts show waning antibody levels starting at about the 180 day mark. This is not definitive, however, and could be skewed by the small sample size.
On average, the natural infection group showed lower neutralization values than the Pfizer and Moderna groups, but the natural infection group did not display the same decline in antibody neutralization.
Results indicate antibodies produced after vaccination or natural infection are less effective against Delta than wild type SARS-CoV-2. Despite this difference, our data shows on average, Delta neutralization is still in the positive range for all cohorts.
Against Delta the J&J group has an average value near the positive-negative cutoff. However, it is unclear what this means in terms of protection. It is also worth noting that our small J&J sample size may skew the data. More testing is needed to improve confidence in those results.
Furthermore, with Delta variant tests we are applying Genscript's suggested positive/negative cutoff value for the WT virus tests. The Delta variant version of their neutralizing antibody test has not been verified, and unlike WT version, does not have FDA Emergency Use Authorization (EUA).
It does appear antibody neutralization begins to wane around 6 months after the Pfizer and Moderna vaccines. This is a typical dynamic for antibody titers after any infection or vaccination. Despite the reduction, both WT and Delta variant neutralization is usually still positive 6-8 months after the first vaccine dose.
The two long term samples from naturally infected individuals remain positive at 9 and 12 months. Study participant CH-AS00061 submitted a sample 364 days after testing positive for COVID-19. Their neutralizing antibody levels against WT and Delta were 89.9% and 80.7%, respectively.
Those high neutralization values may indicate an exposure boosted antibody production during their year of convalescence. Importantly, they did not report an additional infection, nor did any of the other naturally infected participants. This shows the long term protection after recovery from infection.
While the natural infection group has the greatest difference between WT and Delta neutralization, some natural immunity dynamics are not captured by the neutralizing antibody test.
Specifically, the test does not assess binding to other SARS-CoV-2 proteins, such as nucleocapsid. The test also does not capture antibody binding to portions of Spike protein outside the receptor binding domain. It is an important distinction because our previous data shows natural immunity provides a strong antibody response against those parts of the virus.
This has a real world impact, as seen in recent data from Israel. Researchers there showed natural immunity is 13 times more protective against Delta infection than vaccination.
Study participant CH-AS00086 had a natural infection in July of 2021. Due to the high frequency of Delta variant in all COVID-19 infections at that time, it is likely Delta caused their infection. Their antibody test showed ~10% higher Delta neutralization than WT, which agrees with that conclusion.
That suggests Genscript's cPASS platform can be used to differentiate the variant responsible for infection. The observation's caveat is CH-AS00086's viral sample was not sequenced. This means we do not definitively know the variant responsible for infection.
The big unanswered question is, at what neutralizing antibody level does protection begin? Delta neutralization is lower for the vaccine groups but still in the positive range for the test. Reports of Delta breakthrough infections indicate the variant can escape from vaccine immunity. However cPASS derived neutralizing antibody levels are unknown in people with breakthrough infections. This needs to be studied in greater detail.
Perhaps the people who experience vaccination failure never developed a strong antibody response. We have tested samples from a few fully vaccinated, immunocompromised individuals who did not produce antibodies. This unfortunate dynamic provides a mechanism for breakthrough infections. It is also evidence that we need to champion monoclonal antibody treatments, continue to develop effective therapies and encourage antibody testing.
In the future, Cure-Hub will explore ways to define the threshold for immune protection against SARS-CoV-2, the now endemic virus.
After completing screening and informed consent on Cure-Hub's online platform, study participants were mailed a home sample collection kit. Thank you to all who have participated, you helped everyone better understand COVID-19.
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