SARS-CoV-2 Omicron neutralization by therapeutic antibodies, convalescent sera, and post-mRNA vaccine booster

Abstract

The rapid spread of the highly contagious Omicron variant of SARS-CoV-2 along with its high number of mutations in the spike gene has raised alarm about the effectiveness of current medical countermeasures. To address this concern, we measured neutralizing antibodies against Omicron in three important settings: (1) post-vaccination sera after two and three immunizations with the Pfizer/BNT162b2 vaccine, (2) convalescent sera from unvaccinated individuals infected by different variants, and (3) clinical-stage therapeutic antibodies. Using a pseudovirus neutralization assay, we found that titers against Omicron were low or undetectable after two immunizations and in most convalescent sera. A booster vaccination significantly increased titers against Omicron to levels comparable to those seen against the ancestral (D614G) variant after two immunizations. Neither age nor sex were associated with differences in post-vaccination antibody responses. Only three of 24 therapeutic antibodies tested retained their full potency against Omicron and high-level resistance was seen against fifteen. These findings underscore the potential benefit of booster mRNA vaccines for protection against Omicron and the need for additional therapeutic antibodies that are more robust to highly mutated variants.

Factors associated with poor antibody response to third-dose SARS-CoV-2 vaccination in patients with rheumatic and musculoskeletal diseases

“…Many immunosuppressed patients with rheumatic and musculoskeletal disease have a poor antibody response to two-dose SARS-COV-2 mRNA vaccination, 1 , 2 prompting widescale authorisation of a third vaccine dose for these patients. High antibody concentrations are required to overcome immune evasion by variants of concern in immunocompetent patients, 3 and although a third dose augments the immune response against SARS-CoV-2 in some immunosuppressed patients, 4 , 5 it is uncertain whether this response is sufficient for protection. Thus, identifying patients with rheumatic and musculoskeletal disease with poor response following a third dose is important in the selection of appropriate candidates for further medical interventions such as additional vaccine doses or prophylactic therapies.…”

Cross-neutralizing activity against Omicron could be obtained in SARS-CoV-2 convalescent patients who received two doses of mRNA vaccination

“…It was reported that the neutralizing antibody activity against Omicron in convalescent patients who were subsequently vaccinated was around ten times higher than that in fully vaccinated patients without past infection [5,□13]. In the present investigation, the ratios of the neutralizing antibody titer against Omicron relative to the other variants (D614G or Alpha) from vaccinated patients after their recovery ( Figure 2C and 2D ) were almost the same as those against Omicron compared to the D614G in uninfected individuals who received three doses of COVID-19 mRNA vaccine [4,□8,□13]. Although it remains unknown whether one dose is sufficient for convalescent patients with severe symptoms and whether a third dose is necessary for convalescent patients with mild symptoms, our results show that at least two doses of mRNA vaccination to SARS-CoV-2 convalescent patients may induce cross-neutralizing activity against Omicron comparably to three doses of mRNA vaccination to uninfected individuals.…”

“…In the efforts to control the spread of Omicron, a major challenge has been the low seroconversion rates of cross-neutralizing antibody against Omicron in sera of the individuals who are fully COVID-19-vaccinated [2]. A booster dose of an mRNA vaccine for individuals' acquisition of sufficient cross-neutralizing ability has been recommended by several investigators [3][4][5] and our research group [6], but as of this writing the data regarding the crossneutralizing activity against Omicron in COVID-19 convalescent individuals following mRNA vaccination are lacking [5,7,8].…”

SARS-CoV-2 Omicron Variant AI-based Primers

“…Since its detection, B.1.1.529 has started to replace the Delta variant in South Africa [24][25][26] , and early evidence has linked it to an increased risk of reinfection [15][16][17]27 . Due to its highly mutated S protein, B.1.1.529 has been shown to escape the majority of SARS-CoV-2 neutralizing antibodies and retrovirals 12,13,28 (except for ensovibep 29 , remdesivir, molnupiravir and nirmatrelvir 30,31 ). Furthermore, current vaccines technologies tested against B.1.1.529 seem to show lower efficacy 13,23,26,28,32,33 , however vaccine boosters (including heterologous booster) have been shown to help reducing immune escape 31,[34][35][36][37] , and universal vaccines to help fight this variant have been proposed 38,39 .…”

“…Due to its highly mutated S protein, B.1.1.529 has been shown to escape the majority of SARS-CoV-2 neutralizing antibodies and retrovirals 12,13,28 (except for ensovibep 29 , remdesivir, molnupiravir and nirmatrelvir 30,31 ). Furthermore, current vaccines technologies tested against B.1.1.529 seem to show lower efficacy 13,23,26,28,32,33 , however vaccine boosters (including heterologous booster) have been shown to help reducing immune escape 31,[34][35][36][37] , and universal vaccines to help fight this variant have been proposed 38,39 . It is important to note that early data point to a reduced risk of hospital admission among Omicron infected individuals 23,27 , and a reduced risk of severe outcomes among Omicron re-infected individuals earlier infected by the Delta variant 25 .…”