Impact of hybrid immunity booster vaccination and Omicron breakthrough infection on SARS-CoV-2 VOCs cross-neutralization.

The elicitation of cross-variant neutralizing antibodies against SARS-CoV-2 represents a major goal for current COVID-19 vaccine strategies. Additionally, natural infection may also contribute to broaden neutralizing responses. To assess the contribution of vaccines and natural infection, we cross-sectionally analyzed plasma neutralization titers of six groups of individuals, organized according to the number of vaccines they received and their SARS-CoV-2 infection history. Two doses of vaccine had a limited capacity to generate cross-neutralizing antibodies against Omicron variants of concern (VOCs) in uninfected individuals, but efficiently synergized with previous natural immunization in convalescent individuals. In contrast, booster dose had a critical impact on broadening the cross-neutralizing response in uninfected individuals, to level similar to hybrid immunity, while still improving cross-neutralizing responses in convalescent individuals. Omicron breakthrough infection improved cross-neutralization of Omicron subvariants in non-previously infected vaccinated individuals. Therefore, ancestral Spike-based immunization, via infection or vaccination, contributes to broaden SARS-CoV-2 humoral immunity.

Efficacy of SARS-CoV-2 vaccination in patients with monoclonal gammopathies: A cross sectional study.

SARS-CoV-2 vaccination is the most effective strategy to protect individuals with haematologic malignancies against severe COVID-19, while eliciting limited vaccine responses. We characterized the humoral responses following 3 mo after mRNA-based vaccines in individuals at different plasma-cell disease stages: monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and multiple myeloma on first-line therapy (MM), compared with a healthy population. Plasma samples from uninfected MM patients showed lower SARS-CoV-2-specific antibody levels and neutralization capacity compared with MGUS, SMM, and healthy individuals. Importantly, COVID-19 recovered MM individuals presented significantly higher plasma neutralization capacity compared with their uninfected counterparts, highlighting that hybrid immunity elicit stronger immunity even in this immunocompromised population. No differences in the vaccine-induced humoral responses were observed between uninfected MGUS, SMM and healthy individuals. In conclusion, MGUS and SMM patients could be SARS-CoV-2 vaccinated following the vaccine recommendations for the general population, whereas a tailored monitoring of the vaccine-induced immune responses should be considered in uninfected MM patients.

Reduced humoral response 3 months following BNT162b2 vaccination in SARS-CoV-2 uninfected residents of long-term care facilities.

BACKGROUND: SARS-CoV-2 vaccination is the most effective strategy to protect older residents of long-term care facilities (LTCF) against severe COVID-19, but primary vaccine responses are less effective in older adults. Here, we characterised the humoral responses of institutionalised seniors 3 months after they had received the mRNA/BNT162b2 vaccine. METHODS: plasma levels of SARS-CoV-2-specific total IgG, IgM and IgA antibodies were measured before and 3 months after vaccination in older residents of LTCF. Neutralisation capacity was assessed in a pseudovirus neutralisation assay against the original WH1 and later B.1.617.2/Delta variants. A group of younger adults was used as a reference group. RESULTS: three months after vaccination, uninfected older adults presented reduced SARS-CoV-2-specific IgG levels and a significantly lower neutralisation capacity against the WH1 and Delta variants compared with vaccinated uninfected younger individuals. In contrast, COVID-19-recovered older adults showed significantly higher SARS-CoV-2-specific IgG levels after vaccination than their younger counterparts, whereas showing similar neutralisation activity against the WH1 virus and an increased neutralisation capacity against the Delta variant. Although, similarly to younger individuals, previously infected older adults elicit potent cross-reactive immune responses, higher quantities of SARS-CoV-2-specific IgG antibodies are required to reach the same neutralisation levels. CONCLUSIONS: although hybrid immunity seems to be active in previously infected older adults 3 months after mRNA/BNT162b2 vaccination, humoral immune responses are diminished in COVID-19 uninfected but vaccinated older residents of LTCF. These results suggest that a vaccine booster dose should be prioritised for this particularly vulnerable population.

Small form factor flow virometer for SARS-CoV-2.

Current diagnostics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection heavily rely on reverse transcription-polymerase chain reaction (RT-PCR) or on rapid antigen detection tests. The former suffers from long time-to-result and high cost while the latter from poor sensitivity. Therefore, it is crucial to develop rapid, sensitive, robust, and inexpensive methods for SARS-CoV-2 testing. Herein, we report a novel optofluidic technology, a flow-virometry reader (FVR), for fast and reliable SARS-CoV-2 detection in saliva samples. A small microfluidic chip together with a laser-pumped optical head detects the presence of viruses tagged with fluorescent antibodies directly from saliva samples. The technology has been validated using clinical samples with high sensitivity (91.2%) and specificity (90%). Thanks also to its short time-to-result (<30 min) and small size (25 × 30 × 13 cm), which can be further reduced in the future, it is a strong alternative to existing tests, especially for point-of-care (POC) and low resource settings.

Previous SARS-CoV-2 Infection Increases B.1.1.7 Cross-Neutralization by Vaccinated Individuals.

With the spread of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is a need to assess the protection conferred by both previous infections and current vaccination. Here we tested the neutralizing activity of infected and/or vaccinated individuals against pseudoviruses expressing the spike of the original SARS-CoV-2 isolate Wuhan-Hu-1 (WH1), the D614G mutant and the B.1.1.7 variant. Our data show that parameters of natural infection (time from infection and nature of the infecting variant) determined cross-neutralization. Uninfected vaccinees showed a small reduction in neutralization against the B.1.1.7 variant compared to both the WH1 strain and the D614G mutant. Interestingly, upon vaccination, previously infected individuals developed more robust neutralizing responses against B.1.1.7, suggesting that vaccines can boost the neutralization breadth conferred by natural infection.

SARS-CoV-2 infection elicits a rapid neutralizing antibody response that correlates with disease severity.

The protective effect of neutralizing antibodies in SARS-CoV-2 infected individuals is not yet well defined. To address this issue, we have analyzed the kinetics of neutralizing antibody responses and their association with disease severity. Between March and May 2020, the prospective KING study enrolled 72 COVID-19+ participants grouped according to disease severity. SARS-CoV-2 infection was diagnosed by serological and virological tests. Plasma neutralizing responses were assessed against replicative virus and pseudoviral particles. Multiple regression and non-parametric tests were used to analyze dependence of parameters. The magnitude of neutralizing titers significantly increased with disease severity. Hospitalized individuals developed higher titers compared to mild-symptomatic and asymptomatic individuals, which together showed titers below the detection limit in 50% of cases. Longitudinal analysis confirmed the strong differences in neutralizing titers between non-hospitalized and hospitalized participants and showed rapid kinetics of appearance of neutralizing antibodies (50% and 80% of maximal activity reached after 11 and 17 days after symptoms onset, respectively) in hospitalized patients. No significant impact of age, gender or treatment on the neutralizing titers was observed in this limited cohort. These data identify a clear association of humoral immunity with disease severity and point to immune mechanisms other than antibodies as relevant players in COVID-19 protection.