tetano
Editor, Senior Moderator
Front Med (Lausanne)
. 2022 Feb 10;9:811004.
doi: 10.3389/fmed.2022.811004. eCollection 2022.
Molecular and Epidemiological Characterization of Emerging Immune-Escape Variants of SARS-CoV-2
Kei Miyakawa[SUP] 1 [/SUP], Sundararaj Stanleyraj Jeremiah[SUP] 1 [/SUP], Yutaro Yamaoka[SUP] 1 2 [/SUP], Takahiko Koyama[SUP] 3 [/SUP], Reitaro Tokumasu[SUP] 4 [/SUP], Michiharu Kudo[SUP] 4 [/SUP], Hideaki Kato[SUP] 5 [/SUP], Akihide Ryo[SUP] 1 [/SUP]
Affiliations
Abstract
The successive emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has presented a major challenge in the management of the coronavirus disease (COVID-19) pandemic. There are growing concerns regarding the emerging variants escaping vaccines or therapeutic neutralizing antibodies. In this study, we conducted an epidemiological survey to identify SARS-CoV-2 variants that are sporadically proliferating in vaccine-advanced countries. Subsequently, we created HiBiT-tagged virus-like particles displaying spike proteins derived from the variants to analyze the neutralizing efficacy of the BNT162b2 mRNA vaccine and several therapeutic antibodies. We found that the Mu variant and a derivative of the Delta strain with E484K and N501Y mutations significantly evaded vaccine-elicited neutralizing antibodies. This trend was also observed in the Beta and Gamma variants, although they are currently not prevalent. Although 95.2% of the vaccinees exhibited prominent neutralizing activity against the prototype strain, only 73.8 and 78.6% of the vaccinees exhibited neutralizing activity against the Mu and the Delta derivative variants, respectively. A long-term analysis showed that 88.8% of the vaccinees initially exhibited strong neutralizing activity against the currently circulating Delta strain; the number decreased to 31.6% for the individuals at 6 months after vaccination. Notably, these variants were shown to be resistant to several therapeutic antibodies. Our findings demonstrate the differential neutralization efficacy of the COVID-19 vaccine and monoclonal antibodies against circulating variants, suggesting the need for pandemic alerts and booster vaccinations against the currently prevalent variants.
Keywords: SARS-CoV-2; dual antibody cocktail therapy; emerging variants; mRNA vaccine; neutralizing antibodies.
. 2022 Feb 10;9:811004.
doi: 10.3389/fmed.2022.811004. eCollection 2022.
Molecular and Epidemiological Characterization of Emerging Immune-Escape Variants of SARS-CoV-2
Kei Miyakawa[SUP] 1 [/SUP], Sundararaj Stanleyraj Jeremiah[SUP] 1 [/SUP], Yutaro Yamaoka[SUP] 1 2 [/SUP], Takahiko Koyama[SUP] 3 [/SUP], Reitaro Tokumasu[SUP] 4 [/SUP], Michiharu Kudo[SUP] 4 [/SUP], Hideaki Kato[SUP] 5 [/SUP], Akihide Ryo[SUP] 1 [/SUP]
Affiliations
- PMID: 35223905
- PMCID: PMC8866700
- DOI: 10.3389/fmed.2022.811004
Abstract
The successive emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has presented a major challenge in the management of the coronavirus disease (COVID-19) pandemic. There are growing concerns regarding the emerging variants escaping vaccines or therapeutic neutralizing antibodies. In this study, we conducted an epidemiological survey to identify SARS-CoV-2 variants that are sporadically proliferating in vaccine-advanced countries. Subsequently, we created HiBiT-tagged virus-like particles displaying spike proteins derived from the variants to analyze the neutralizing efficacy of the BNT162b2 mRNA vaccine and several therapeutic antibodies. We found that the Mu variant and a derivative of the Delta strain with E484K and N501Y mutations significantly evaded vaccine-elicited neutralizing antibodies. This trend was also observed in the Beta and Gamma variants, although they are currently not prevalent. Although 95.2% of the vaccinees exhibited prominent neutralizing activity against the prototype strain, only 73.8 and 78.6% of the vaccinees exhibited neutralizing activity against the Mu and the Delta derivative variants, respectively. A long-term analysis showed that 88.8% of the vaccinees initially exhibited strong neutralizing activity against the currently circulating Delta strain; the number decreased to 31.6% for the individuals at 6 months after vaccination. Notably, these variants were shown to be resistant to several therapeutic antibodies. Our findings demonstrate the differential neutralization efficacy of the COVID-19 vaccine and monoclonal antibodies against circulating variants, suggesting the need for pandemic alerts and booster vaccinations against the currently prevalent variants.
Keywords: SARS-CoV-2; dual antibody cocktail therapy; emerging variants; mRNA vaccine; neutralizing antibodies.