Friday, July 02, 2021

PrePrint: Infectivity and Immune Escape of the New SARS-CoV-2 Variant of Interest Lambda


 WHO List of VOCs (Variants of Concern) & VOIs (Variants of Interest) 

#16,046

Although there are literally thousands of SARS-CoV-2 variants around the world, only a handful have been identified as having traits that make them more worrisome than the `wild-type' COVID we've been dealing with for nearly 18 months (see WHO list above). 

The latest addition to that shortlist is dubbed Lambda, and as befits its very recent inclusion, very little scientific research has been released on this variant.  Anecdotal reports from South America, however, suggest it may be more transmissible. 

Lambda (Pango lineage C.37) was added to the WHO's VOI list on June 14th (see WHO Adds Lambda VOI (Variant of Interest) To Their Watchlist), with the WHO stating:

Lambda has been associated with substantive rates of community transmission in multiple countries, with rising prevalence over time concurrent with increased COVID-19 incidence. The earliest sequenced samples were reported from Peru in August 2020.

(Snip)

It is characterised by mutations in the spike protein, including G75V, T76I, del247/253, L452Q, F490S, D614G and T859N; however, there is currently limited evidence on the full extent of the impact associated with these genomic changes, and further robust studies into the phenotypic impacts are needed to better understand the impact on countermeasures and to control the spread.

Further studies are also required to validate the continued effectiveness of vaccines.

While the Delta variant - which is rapidly rising around the globe - remains our most immediate concern, the pattern we've seen with these rising COVID stars is that they eventually peak, and then they are challenged by the next viral contender.   

The B.1.2 variant, which reigned in the United States until early 2021 was supplanted by Alpha (B.1.1.7) in the spring, which is now being challenged by Delta (B.1.617.2) and to a lesser extent Gamma (P.1).  

Whether Lambda, P.1., AY.1 (the Delta Variant with the K417N mutation), or some other emerging variant has what it takes to challenge Delta's dominance remains to be seen.  But since SARS-CoV-2 continues to evolve, it is worth looking down the road to see what might be the next challenge. 

To that end we have a preprint (non-yet peer reviewed) article on the new Lambda variant currently rife in Chile, that finds it has the ability to evade some of the protection offered by the the widely used Chinese made CoronaVac vaccine.

Chile, while having a high rate of vaccine uptake, continues to struggle with COVID (see June 11th report Chile shuts capital Santiago once more as vaccines fail to quell rampant cases).   Some excerpts from the preprint follow, but click the link to read it in its entirety.  I'll have a brief postscript when you return.


Infectivity and immune escape of the new SARS-CoV-2 variant of interest Lambda

Mónica L. Acevedo1*, Luis Alonso-Palomares1*, Andrés Bustamante1 , Aldo Gaggero3, Fabio Paredes4, Claudia P. Cortés2,5, Fernando Valiente-Echeverría1#, Ricardo Soto-Rifo1#

ABSTRACT

Background: The newly described SARS-CoV-2 lineage C.37 was recently classified as a
variant of interest by the WHO (Lambda variant) based on its high circulation rates in South  American countries and the presence of critical mutations in the spike protein. The impact of such mutations in infectivity and immune escape from neutralizing antibodies are entirely unknown.

Methods: We performed a pseudotyped virus neutralization assay and determined the impact of the Lambda variant on infectivity and immune escape using plasma samples from healthcare workers (HCW) from two centers in Santiago, Chile who received the two-doses scheme of the inactivated virus vaccine CoronaVac.

Results: We observed an increased infectivity mediated by the Lambda spike protein that was even higher than that of the D614G (lineage B) or the Alpha and Gamma variants. Compared to the Wild type (lineage A), neutralization was decreased by 3.05-fold for the Lambda variant while it was 2.33-fold for the Gamma variant and 2.03-fold for the Alpha variant.

Conclusions: Our results indicate that mutations present in the spike protein of the Lambda variant of interest confer increased infectivity and immune escape from neutralizing antibodies elicited by CoronaVac. These data reinforce the idea that massive vaccination campaigns in countries with high SARS-CoV-2 circulation must be accompanied by strict genomic surveillance allowing the identification of new isolates carrying spike mutations and immunology studies aimed to determine the impact of these mutations in immune escape and vaccines breakthrough.

          (SNIP) 

DISCUSSION

High SARS-CoV-2 transmission is occurring in Chile despite an intensive vaccination campaign, which mostly relies in the inactivated virus vaccine from Sinovac Biotech and to a lesser extent in the mRNA vaccine from Pfizer/BioNTech and the non-replicative viral vector vaccines from Oxford/AstraZeneca and Cansino Biologicals. The last surge reported in the country has been dominated by the SARS-CoV-2 variants Gamma and Lambda, the former classified as a variant of concern several months ago and the latter being recently recognized as a variant of interest by the WHO.

While the Gamma variant possess 11 mutations in the spike protein including those in the receptor binding domain (RBD) associated with increased ACE2 binding and infectivity (N501Y) or immune escape (K417T and E484K)1 , the spike protein of the Lambda variant has a unique pattern of 7 mutations (Δ246-252, G75V, T76I, L452Q, F490S, D614G, T859N) from which L452Q is similar to the L452R mutation reported in the Delta and Epsilon variants6. 

The L452R mutation has been shown to confer immune escape to monoclonal antibodies (mAbs) as well as convalescent plasma13–16. Moreover, the L452R mutation has also been shown to increase viral infectivity16 and our data suggest that the L452Q mutation present in the Lambda variant might confer similar properties to those described for L452R. 

Interestingly, the 246-252 deletion in the N-terminal domain (NTD) of the Lambda Spike is located in an antigenic supersite17–20 and therefore, this deletion might also contribute to immune escape. Moreover, the F490S mutation has also been associated with an escape to convalescent sera13. Consistent with these antecedents, our results indicate that the spike protein of the Lambda variant confers immune escape to neutralizing antibodies elicited by the CoronaVac vaccine. Whether the Lambda variant also escapes to the cellular response shown to be elicited by CoronaVac9 is still unknown. 

We also observed that the spike protein of the Lambda variant presented increased infectivity when compared with the spike protein of the Alpha and Gamma variants, both of them with reported increased infectivity and transmissibility21,22. 

Together, our data show for the first time that mutations present in the spike protein of the Lambda variant confer escape to neutralizing antibodies and increased infectivity. The evidence presented here reinforces the idea that massive vaccination campaigns in countries with high SARS-CoV-2 circulation rates must be accompanied by strict genomic surveillance aimed to rapidly identify new viral isolates carrying spike mutations as well as studies aimed to analyze the impact of these mutations in immune escape and vaccines breakthrough.



Reduced vaccine protection doesn't mean no protection of course, and since most of those vaccinated in Chile received the inactivated-virus CoronaVac - and not the mRNA vaccines primarily adopted for use in the the United States -  our experiences with Lambda may differ. 

Still, SARS-CoV-2 continues to show its ability to evolve and offer up new challenges. And in order to meet them, we need as much advance knowledge of where they are heading that we can get.