Credit NIAID
17,250
Eighteen months ago, when many world leaders were touting the `imminent end of the pandemic' the UK's SAGE (Scientific Advisory Group for Emergencies) on COVID released a series of detailed reports on the SARS-CoV-2 pandemic, and potential future scenarios.
Among their concerns, they warned of:
- The emergence of a much more severe variant
- Decreasing vaccine effectiveness
- And the emergence of drug resistant variants
While their first `worst case' scenario (emergence of a more severe variant) has thankfully not occurred, we did end up with an extremely transmissible and highly mutable Omicron variant - which has helped to drive scenarios #2 and #3.
Due to declining COVID vaccine effectiveness, a new bivalent booster shot was approved last fall, but uptake has been disappointing.
Between vaccine fatigue, incessant and misleading anti-vaccine messaging online (see No. XBB.1.5 Is Not More Likely To infect the Vaccinated (vs. Unvaccinated)), and assurances from politicians and pundits that the `COVID emergency' was over, fewer than 20% of the population has elected to get the new booster.
As we move into the 4th year of this pandemic, the SARS-CoV-2 virus continues to evolve, mutating rapidly and producing increasingly transmissible, and immunity evading, variants.
We've seen XBB.1.5 described as the `most transmissible, and immune evasive' to date, but - as today's preprint indicates - it may already have some serious competition.
While we've discussed XBB.1.5 extensively over the past couple of months, CA.3.1 and CH.1.1 have received far less attention, although the UK recently reported that CH.1.1 made up nearly 20% of local cases.
Both carry the L452R substitution in the spike, previously discovered in the Delta and Omicron BA.4/5 variants.
All of which brings us to a new preprint from researchers at Ohio State University, which looks at the `extraordinary' immune evasion of these new Omicron variants.
They report `a nearly complete escape of these variants from neutralizing antibodies stimulated by three doses of mRNA vaccine', but suggest that neutralization can be improved (2~8-fold higher nAb titers) by receipt of the bivalent booster.
They caution, however, that both the CH.1.1 and CA.3.1 variants were `highly resistant to both monovalent and bivalent mRNA vaccinations. I've only reproduced the abstract below, along with some excerpts from the full 28-page PDF.
I'll have a brief postscript after the break.
Extraordinary Evasion of Neutralizing Antibody Response by Omicron XBB.1.5, CH.1.1 and CA.3.1 VariantsPanke Qu, Julia N. Faraone, John P. Evans, Yi-Min Zheng, Claire Carlin, Mirela Anghelina, Patrick Stevens, Soledad Fernandez, Daniel Jones, Ashish Panchal, Linda J. Saif, Eugene M. Oltz, Kai Xu, Richard J. Gumina, Shan-Lu Liudoi: https://doi.org/10.1101/2023.01.16.524244
Abstract
Newly emerging Omicron subvariants continue to emerge around the world, presenting potential challenges to current vaccination strategies. This study investigates the extent of neutralizing antibody escape by new subvariants XBB.1.5, CH.1.1, and CA.3.1, as well as their impacts on spike protein biology.Our results demonstrated a nearly complete escape of these variants from neutralizing antibodies stimulated by three doses of mRNA vaccine, but neutralization was rescued by a bivalent booster. However, CH.1.1 and CA.3.1 variants were highly resistant to both monovalent and bivalent mRNA vaccinations.We also assessed neutralization by sera from individuals infected during the BA.4/5 wave of infection and observed similar trends of immune escape. In these cohorts, XBB.1.5 did not exhibit enhanced neutralization resistance over the recently dominant BQ.1.1 variant. Notably, the spike proteins of XBB.1.5, CH.1.1, and CA.3.1 all exhibited increased fusogenicity compared to BA.2, correlating with enhanced S processing.Overall, our results support the administration of new bivalent mRNA vaccines, especially in fighting against newly emerged Omicron subvariants, as well as the need for continued surveillance of Omicron subvariants.
(SNIP)
Discussion
As SARS-CoV-2 continues to mutate and evolve, it is critical to monitor how the biology of the virus changes and the impact on the efficacy of current vaccines, including the currently bivalent mRNA vaccines. In this work, we found that the bivalent mRNA vaccine recipients exhibit approximately 2~8-fold higher nAb titers, depending on variants tested, as compared to monovalent booster recipients, and the results are consistent with enhanced vaccine efficacy for the bivalent formula34 .
The nearly complete escape of 3-dose sera and BA.4/5 wave infection exhibited by all Omicron subvariants, especially XBB subvariants and CH.1.1 and CA.3.1, was remarkable and this is supported by some recent studies23,24,27,35–37 . Notably, XBB.1.5 did not exhibit enhanced neutralization resistance over the recently dominant BQ.1.1 variant, which itself caused no notable surge in cases or hospitalizations compared to prior Omicron subvariants.
Due to the fact that most samples fell below the limit of nAb detection, it is difficult to compare the neutralization titers between the different subvariants for this cohort. However, it is clear that CH.1.1 and CA.3.1 have a consistently stronger neutralization resistance than XBB, XBB.1 and XBB.1.5, which is astonishing and warrants continuous monitoring and further investigations.
Overall, our study highlights the continued waning of 3-dose mRNA booster efficacy against newly emerging Omicron subvariants. This effect can be partially saved by administration of a bivalent booster, though escape by some subvariants, particularly CH.1.1 and CA.3.1, is still prominent. Continued refinement of current vaccination strategies or investigation of new ones remains necessary. The biology of the S protein of Omicron subvariants, notably those of the XBB lineage, also continues to change, emphasizing the importance of continued surveillance of emerging variants.
It isn't often that you see the words `extraordinary', `astonishing', `notably' (x7), `surprisingly, and `remarkable' all appearing within a single scientific report, yet here we have one. The authors are obviously concerned over the future trajectory of these new variants.
Even if we are lucky enough to avoid the #1 scenario proffered by the SAGE committee, the long-term public health impact of repeated `mild' COVID infections is increasingly under scrutiny (see Nature: Acute and Postacute Sequelae Associated with SARS-CoV-2 Reinfection).The good news is, the bivalent booster appears to provide improved protection over earlier vaccine formulations (see MMWR: 2 Early Estimates Of Effectiveness Of Bivalent COVID Booster In Preventing Medical Encounters), but there are no guarantees how that will last.
