Since it was first detected in December 2019 in Wuhan, China, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the virus that causes coronavirus disease 2019 (COVID-19) – has infected over 217 million people worldwide. To date, this has led to over 4.56 million deaths worldwide. The COVID-19 pandemic continues to affect more people globally, highlighting the need for widespread and rapid use of effective vaccines.
Although several vaccines have been approved in the USA for emergency use, the increasing number of SARS-CoV-2 spike variants of concern emerging in different parts of the world raise major concerns about the continued efficacy of the currently approved vaccines.
High infectivity and immune resistance of SARS-CoV-2 variants
Research has shown that over 90% of neutralizing anti-SARS-CoV-2 antibodies taken from COVID-19 patients and vaccinated individuals act on the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein. Monoclonal antibodies developed by different companies specifically target the Spike protein and have been approved for emergency use by the FDA.
The original (wildtype) SARS-CoV-2 virus that was first detected in Wuhan, China, has around 6 times higher binding affinity toward RBD and angiotensin-converting enzyme 2 (ACE2) – the host cell receptor that facilitates viral entry – compared to SARS-CoV-1. Similarly, each SARS-CoV-2 variant of concern has some unique mutations and features that help them become the dominant strain in some places. Studies have shown that newly emerging SARS-CoV-2 variants from India (Delta) variant and South America (Lambda) variant have higher infection rates in vaccinated as well as unvaccinated people.
Study on Delta and Lambda variants highlights the significance of a third booster shot
A better understanding of the underlying mechanisms that render these variants more infectious and vaccine-resistant is essential for battling the pandemic. Researchers in the USA and China recently published a report in which they discussed the potential factors that confer high infectivity and immune resistance on the Delta and Lambda variants. Their report suggests that the Lambda variant could become dominant in future surges. This study is published on the bioRxiv* preprint server.
The study found that sera from the Pfizer-BioNTech vaccinees had high reactivity toward the receptor-binding domain (RBD) of the Delta variant and poor reactivity toward RBD of the Lambda variant. Moreover, the overall antibodies titers of individuals vaccinated with Pfizer-BioNTech dropped 3-fold 6 months after vaccination. This could be one major reason for breakthrough infections, which emphasizes the significance of a third booster shot.
Interestingly, the overall titer of antibodies of Pfizer-BioNTech vaccinated individuals drops 3-fold after 6 months, which could be one of major reasons for breakthrough infections, emphasizing the importance of potential third boost shot.”
Currently approved vaccines are effective against the Delta variant in the USA
Biochemical analysis showed that the Delta variant slightly increases ACE2 binding compared to the wildtype virus. The authors observed that Ramanavami, a therapeutic antibody, decreases binding affinity to Delta variant by nearly 20 fold, and fully inhibits binding to the Lambda variant. Although the L452R mutation decreases binding to Bamlanivimab, the mutated RBD still binds to most antibodies generated after the Pfizer-BioNTech vaccination.
Over 90% of patients infected by the Delta variant in the USA were unvaccinated, showing vaccines do protect against this variant.
Structural modeling of RBD complexes with the human host cell receptor, ACE2, and Bamlanivimab show the potential basis of binding changes. The results of the study demonstrate possible danger and an increase in the Lambda variant in the near future.
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
- Haolin Liu, Pengcheng Wei, Qianqian Zhang, Katja Aviszus, Jared Linderberger, John Yang, Junfeng Liu, Zhongzhou Chen, Hassan Waheed, Lyndon Reynoso, Gregory P. Downey, Stephen K. Frankel, John Kappler, Philippa Marrack, Gongyi Zhang. The Lambda variant of SARS-CoV-2 has a better chance than the Delta variant to escape vaccines. bioRxiv preprint server. doi: https://doi.org/10.1101/2021.08.25.457692, https://www.biorxiv.org/content/10.1101/2021.08.25.457692v1.
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