Ancestral SARS‐CoV‐2 and Omicron BA.5‐specific neutralizing antibody and T‐cell responses after Omicron bivalent booster vaccination in previously infected and infection‐naive individuals

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Abstract

Coronavirus disease‐2019 (COVID‐19) bivalent ancestral/Omicron messenger RNA (mRNA) booster vaccinations became available to boost and expand the immunity against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) Omicron infections. In a prospective cohort study including 59 healthcare workers, we assessed SARS‐CoV‐2 ancestral and Omicron BA.5‐specific neutralizing antibody and T‐cell responses in previously infected and infection‐naive individuals. Also, we assessed the effect of an ancestral/Omicron BA.1 bivalent mRNA booster vaccination on these immune responses. 10 months after previous monovalent mRNA vaccinations, ancestral SARS‐CoV‐2 S1‐specific T‐cell and anti‐RBD IgG responses remained detectable in most individuals and a previous SARS‐CoV‐2 infection was associated with increased T‐cell responses. T‐cell responses, anti‐RBD IgG, and Omicron BA.5 neutralization activity increased after receiving an ancestral/Omicron BA.1 bivalent booster mRNA vaccination. An Omicron BA.5 infection in addition to bivalent vaccination, led to a higher ratio of Omicron BA.5 to ancestral strain neutralization activity compared to no bivalent vaccination and no recent SARS‐CoV‐2 infection. In conclusion, SARS‐CoV‐2 T‐cell and antibody responses persist for up to 10 months after a monovalent booster mRNA vaccination. An ancestral/Omicron BA.1 bivalent booster mRNA vaccination increases these immune responses and also induces Omicron BA.5 cross‐neutralization antibody activity. Finally, our data indicate that hybrid immunity is associated with improved preservation of T‐cell immunity.

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Increased risk of SARS-CoV-2 reinfection associated with emergence of Omicron in South Africa

Juliet Pulliam, Cari van Schalkwyk, Nevashan Govender … (2022)

Here, we provide two methods for monitoring reinfection trends in routine surveillance data to identify signatures of changes in reinfection risk and apply these approaches to data from South Africa’s SARS-CoV-2 epidemic to date. While we found no evidence of increased reinfection risk associated with circulation of Beta (B.1.351) or Delta (B.1.617.2) variants, we find clear, population-level evidence to suggest immune evasion by the Omicron (B.1.1.529) variant in previously infected individuals in South Africa. Reinfections occurring between 01 November 2021 and 31 January 2022 were detected in individuals infected in all three previous waves, and there has been an increase in the risk of having a third infection since mid-November 2021.

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Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum

Aekkachai Tuekprakhon, Jiandong Huo, Rungtiwa Nutalai … (2022)

The Omicron lineage of SARS-CoV-2, first described in November 2021, spread rapidly to become globally dominant and has split into a number of sub-lineages. BA.1 dominated the initial wave but has been replaced by BA.2 in many countries. Recent sequencing from South Africa’s Gauteng region uncovered two new sub-lineages, BA.4 and BA.5 which are taking over locally, driving a new wave. BA.4 and BA.5 contain identical spike sequences and, although closely related to BA.2, contain further mutations in the receptor binding domain of spike. Here, we study the neutralization of BA.4/5 using a range of vaccine and naturally immune serum and panels of monoclonal antibodies. BA.4/5 shows reduced neutralization by serum from triple AstraZeneca or Pfizer vaccinated individuals compared to BA.1 and BA.2. Furthermore, using serum from BA.1 vaccine breakthrough infections there are likewise, significant reductions in the neutralization of BA.4/5, raising the possibility of repeat Omicron infections. SARS-CoV-2 Omicron BA.4 and BA.5 sublineages bear mutations that lead to their reduced neutralization by sera from triple vaccinated individuals when compared to the more recent BA.1 and BA.2. Importantly, sera from individuals with breakthrough BA.1 infections also show reduced neutralization, suggesting that repeat Omicron infections are likely in the population.

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SARS-CoV-2 variant biology: immune escape, transmission and fitness

Alessandro M. Carabelli, Thomas P. Peacock, Lucy G. Thorne … (2023)

In late 2020, after circulating for almost a year in the human population, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibited a major step change in its adaptation to humans. These highly mutated forms of SARS-CoV-2 had enhanced rates of transmission relative to previous variants and were termed ‘variants of concern’ (VOCs). Designated Alpha, Beta, Gamma, Delta and Omicron, the VOCs emerged independently from one another, and in turn each rapidly became dominant, regionally or globally, outcompeting previous variants. The success of each VOC relative to the previously dominant variant was enabled by altered intrinsic functional properties of the virus and, to various degrees, changes to virus antigenicity conferring the ability to evade a primed immune response. The increased virus fitness associated with VOCs is the result of a complex interplay of virus biology in the context of changing human immunity due to both vaccination and prior infection. In this Review, we summarize the literature on the relative transmissibility and antigenicity of SARS-CoV-2 variants, the role of mutations at the furin spike cleavage site and of non-spike proteins, the potential importance of recombination to virus success, and SARS-CoV-2 evolution in the context of T cells, innate immunity and population immunity. SARS-CoV-2 shows a complicated relationship among virus antigenicity, transmission and virulence, which has unpredictable implications for the future trajectory and disease burden of COVID-19.