SARS-CoV-2 variants with reduced infectivity and varied sensitivity to the BNT162b2 vaccine are developed during the course of infection

Abstract

In-depth analysis of SARS-CoV-2 quasispecies is pivotal for a thorough understating of its evolution during infection. The recent deployment of COVID-19 vaccines, which elicit protective anti-spike neutralizing antibodies, has stressed the importance of uncovering and characterizing SARS-CoV-2 variants with mutated spike proteins. Sequencing databases have allowed to follow the spread of SARS-CoV-2 variants that are circulating in the human population, and several experimental platforms were developed to study these variants. However, less is known about the SARS-CoV-2 variants that are developed in the respiratory system of the infected individual. To gain further insight on SARS-CoV-2 mutagenesis during natural infection, we preformed single-genome sequencing of SARS-CoV-2 isolated from nose-throat swabs of infected individuals. Interestingly, intra-host SARS-CoV-2 variants with mutated S genes or N genes were detected in all individuals who were analyzed. These intra-host variants were present in low frequencies in the swab samples and were rarely documented in current sequencing databases. Further examination of representative spike variants identified by our analysis showed that these variants have impaired infectivity capacity and that the mutated variants showed varied sensitivity to neutralization by convalescent plasma and to plasma from vaccinated individuals. Notably, analysis of the plasma neutralization activity against these variants showed that the L1197I mutation at the S2 subunit of the spike can affect the plasma neutralization activity. Together, these results suggest that SARS-CoV-2 intra-host variants should be further analyzed for a more thorough characterization of potential circulating variants.

Immunological Study of Combined Administration of SARS-CoV-2 DNA Vaccine and Inactivated Vaccine

“…One is that antibody titers elicited by COVID-19 vaccines declined quickly, and the ability to target certain SARS-CoV-2 variants decreased even more quickly [45][46][47]. The other is that new variants are constantly emerging and becoming the main infectious strains in different regions [48][49][50]. Thus, considering that inactivated vaccines are currently among the most widely used vaccines in the world, and considering their inherent disadvantages, we constructed two DNA vaccine candidates that could cover more variants of SARS-CoV-2 and tested their administration with inactivated vaccines in various combinations.…”

Pharmaceutical Prospects of Curcuminoids for the Remedy of COVID-19: Truth or Myth

“…Intensely, BNT and Moderna vaccines have been currently approved by the FDA ( Chilamakuri and Agarwal 2021 ). Within 2 years, there are several mutated variants of SARS-CoV-2 from the origin strain, and their wide dispersion led to multiple waves of outbreaks, especially the mutation on the spike gene of new SARS-CoV-2 variants caused the alteration in several amino acid residues and change the structural conformation of spike protein, decreasing the titer of human antibodies and neutralizing antibodies induced by infection or vaccination ( Khateeb et al, 2022 ; Ma et al, 2022 ; Tay et al, 2022 ). New antibody-resistant variants of SARS-CoV-2 in vaccine breakthrough infection can be seen even in people who have received two or three vaccinations within 6 months which shows that the vaccines have failed to fully protect the people from variants of SARS-CoV-2 infection such as Omicron ( Khateeb et al, 2022 ; Servellita et al, 2022 ; Wang et al, 2022 ).…”

Persistent SARS-CoV-2 Alpha Variant Infection in Immunosuppressed Patient, France, February 2022

“…In January 2022, the Alpha variant was no longer circulating in France, according to strains submitted to GISAID. Our case highlights the potential for persistence of supposedly extinct SARS-CoV-2 variants that might cause prolonged infection in immunocompromised patients and acquire adaptive mutations that confer increased transmissibility, antigenic divergence, and reduced pathogenicity, with obvious public health implications ( 1 , 3 ). Similar cases likely exist in other parts of the world because SARS-CoV-2 genome sequencing and reporting to GISAID are far from exhaustive.…”

“…I mmunosuppressed patients can have prolonged SARS-CoV-2 infection (1). Studies have reported the occurrence and selection of multiple mutations in the spike glycoprotein sequence in immunosuppressed patients with persistent SARS-CoV-2 infections (2)(3)(4)(5)(6). To date, intrahost mutations have been described essentially in the ancestral wild-type SARS-CoV-2 virus (3,(5)(6)(7)(8), especially during prolonged infection with variants of concern (VOCs) (9).…”

“…Studies have reported the occurrence and selection of multiple mutations in the spike glycoprotein sequence in immunosuppressed patients with persistent SARS-CoV-2 infections (2)(3)(4)(5)(6). To date, intrahost mutations have been described essentially in the ancestral wild-type SARS-CoV-2 virus (3,(5)(6)(7)(8), especially during prolonged infection with variants of concern (VOCs) (9). Additional SARS-CoV-2 mutations in immunocompromised persons could enable increased virus transmissibility and immune evasion, shaping the emergence of new VOCs.…”