Characterisation of a new recombinant, #XD (a Delta-Omicron recombinant)
➡️ The XD is a chimeric SARS2 virus having recombination of Delta AY.4 & Omicron BA.1.
➡️ The XD spike carries a larger fraction of the signature changes of BA.1, including the entirety of the RBD
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➡️ The XD is a chimeric SARS2 virus having recombination of Delta AY.4 & Omicron BA.1.
➡️ The XD spike carries a larger fraction of the signature changes of BA.1, including the entirety of the RBD
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There are two breakpoints, one at the beginning of spike & one within ORF 3a
➡️ Immune escape:
-With pseudovirus, only a small reduction in NAb titers ag #Delta compared to WT
-In contrast, both XD & BA.1 were barely neutralized by sera sampled 1 or 6 mo after 2 doses
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➡️ Immune escape:
-With pseudovirus, only a small reduction in NAb titers ag #Delta compared to WT
-In contrast, both XD & BA.1 were barely neutralized by sera sampled 1 or 6 mo after 2 doses
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-The titers were all much higher 1 month after a 3rd immunization, although they displayed an 8-fold to 10-fold reduction in neutralization efficacy against both BA.1 and XD compared to the WT virus.
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Likewise, in individuals infected and vaccinated with one dose, NAb titers towards BA.1 and XD were reduced 3.4- and 3.7-fold (but not significant), respectively
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➡️ Intrinsic severity of XD
Researchers infected hACE2-mice with test dose of either the recombinant or each parental lineage virus. They compared the viral load in the lungs & nasal turbinates at 3 days post-infection. 5/
Researchers infected hACE2-mice with test dose of either the recombinant or each parental lineage virus. They compared the viral load in the lungs & nasal turbinates at 3 days post-infection. 5/
The levels of viral RNA in the lungs of mice infected with BA.1 or XD viruses were comparable, and 3.7-fold lower than those of AY.4-infected animals
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In contrast, the viral load in nasal turbinates of the XD-infected mice was 8.5-fold higher than that in BA.1-infected animals, & only slightly lower than that of AY.4 infected mice
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They also monitored mice for body weight loss and disease over 11 days. Like the main Delta lineage, the parental AY.4 isolate resulted in disease with weight loss that accelerated at 3 dpi, and 6/7 mice reached humane endpoints between dpi 7 and 9.
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BA.1 infection was not associated with weight loss nor lethality.
With the XD virus, no weight loss during the first 5 dpi was observed, but all mice deteriorated rapidly between day 5 and 8 and died or had to be euthanized by day 9.
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With the XD virus, no weight loss during the first 5 dpi was observed, but all mice deteriorated rapidly between day 5 and 8 and died or had to be euthanized by day 9.
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These results indicate that #XD is associated w/ clinical features distinct from those of BA.1 in hACE2-mice
It further suggests that attenuated phenotype of BA.1 in this model cannot be only linked to variations in spike such as in the RBD or near the furin cleavage site 10/
It further suggests that attenuated phenotype of BA.1 in this model cannot be only linked to variations in spike such as in the RBD or near the furin cleavage site 10/
Conclusions:
The XD recombinant exhibits immune escape properties similar to Omicron, while its behavior in mice expressing the human ACE2 receptor is more similar to Delta. 11/
The XD recombinant exhibits immune escape properties similar to Omicron, while its behavior in mice expressing the human ACE2 receptor is more similar to Delta. 11/
Though this XD recombinant looks more threatening than XE or all other BA.1 X BA.2 recombinants, but does not seem to outcompete current dominant lineage BA.2
The one to watch is Delta X BA.2 spike recombinant!! 12/
researchsquare.com/article/rs-150…
The one to watch is Delta X BA.2 spike recombinant!! 12/
researchsquare.com/article/rs-150…
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