Convergent epitope specificities, V gene usage and public clones elicited by primary exposure to SARS-CoV-2 variants

An important consequence of infection with a SARS-CoV-2 variant is protective humoral immunity against other variants. The basis for such cross-protection at the molecular level is incompletely understood. Here we characterized the repertoire and epitope specificity of antibodies elicited by Beta, Gamma and ancestral variant infection and assessed their cross-reactivity to these and the more recent Delta and Omicron variants. We developed a high-throughput approach to obtain immunoglobulin sequences and produce monoclonal antibodies for functional assessment from single B cells. Infection with any variant elicited similar cross-binding antibody responses exhibiting a remarkably conserved hierarchy of epitope immunodominance. Furthermore, convergent V gene usage and similar public B cell clones were elicited regardless of infecting variant. These convergent responses despite antigenic variation may represent a general immunological principle that accounts for the continued efficacy of vaccines based on a single ancestral variant.

T cell response following anti COVID-19 BNT162b2 vaccination is maintained against the SARS-CoV-2 Omicron B.1.1.529 variant of concern

The progression of the COVID-19 pandemic leads to the emergence of variants of concern (VOC), which may compromise the efficacy of the currently administered vaccines. Antigenic drift can potentially bring about a reduced protective T cell immunity and consequently to more severe disease manifestations. To assess this possibility, the T cell responses to the wild-type, Wuhan-1 SARS-CoV-2 ancestral spike protein and Omicron B.1.1.529 spike protein were compared. Accordingly, peripheral blood mononuclear cells (PBMC) were collected from 8 healthy volunteers 4-5 months following a third vaccination with BNT162b2, and stimulated with overlapping peptide libraries representing the spike of either the ancestral or Omicron SARS-CoV- 2 virus variants. Quantification of the specific T cells was carried out by a fluorescent ELISPOT assay, monitoring interferon-gamma (IFNg), interleukin-10 (IL-10) and interleukin-4 (IL-4) secreting cells. For all the examined individuals, comparable level of reactivity to both forms of spike protein were determined. In addition, a dominant Th1 response was observed, manifested mainly by IFNg secreting cells and only limited numbers of IL-10 and IL-4 secreting cells. The data demonstrates a stable T cell activity to the emerging Omicron variant in the tested individuals, therefore the protective immunity to the variant following BNT162b2 vaccination is not significantly affected.

Knowledge of and willingness to take pre-exposure prophylaxis among men who have sex with men in Israel.

BACKGROUND: Oral pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) has been found to reduce viral acquisition among HIV-negative MSM. This cross-sectional study was conducted before pre-exposure prophylaxis (PrEP) licensure in Israel, and aimed to compare men who have sex with men (MSM) who had heard of PrEP with those who had not, as well as MSM willing to take PrEP with those who were hesitant or not willing to take PrEP. METHODS: HIV-negative MSM responded anonymously to questionnaires in 2017 regarding their knowledge of and willingness to take PrEP, prior use of PrEP and post-exposure prophylaxis (PEP), and their sexual behaviors. RESULTS: Among 1705 participants, 1431 (83.9%) had heard about PrEP. They were older and more often reported being Jewish, having an academic degree, self-identifying as gay/bisexual, being tested for HIV in the last year, participating in group sex, using alcohol or drugs before or during sex, and having prior use of PrEP/PEP compared with MSM who had not heard about PrEP. A total of 760 (44.8%) participants indicated that they would consider taking PrEP, 567 (33.5%) maybe would consider taking PrEP, and 367 (21.7%) would not take PrEP. Those who were willing to take PrEP had a lower level of education, were involved in high-risk sexual behaviors, used alcohol or drugs before or during sex, and had previously used PrEP/PEP compared with participants who maybe would consider taking or would not take PrEP. When participants were asked to indicate if they were willing to take PrEP at different potential efficacies and costs, the willingness to using PrEP increased with the potential efficacy of the drug and adversely related to its cost. CONCLUSIONS: PrEP awareness was high, and 44.8% indicated willingness to take PrEP, especially those who reported high-risk sexual behaviors. This supports the current policy in Israel to allow PrEP to MSM who are at high-risk. In order to maintain a high level of PrEP-adherence, physicians should consider structural barriers, such as negative stigma of being promiscuous, lack of perceived HIV-risk, difficulties in accessing clinics or paying for PrEP, inability to follow-up or low tolerability of the medication.

Multiplexed Detection of COVID-19 with Single-Molecule Technology

The COVID-19 pandemic raises the need for diverse diagnostic approaches to rapidly detect different stages of viral infection. The flexible and quantitative nature of single-molecule imaging technology renders it optimal for development of new diagnostic tools. Here we present a proof-of-concept for a single-molecule based, enzyme-free assay for detection of SARS-CoV-2. The unified platform we developed allows direct detection of the viral genetic material from patients samples, as well as their immune response consisting of IgG and IgM antibodies. Thus, it establishes a platform for diagnostics of COVID-19, which could also be adjusted to diagnose additional pathogens.