Neutralising reactivity against SARS-CoV-2 delta and omicron variants by vaccination and infection history.

BACKGROUND: The continuous emergence of SARS-CoV-2 variants of concern (VOC) with immune escape properties, such as Delta (B.1.617.2) and Omicron (B.1.1.529), questions the extent of the antibody-mediated protection against the virus. Here we investigated the long-term antibody persistence in previously infected subjects and the extent of the antibody-mediated protection against B.1, B.1.617.2 and BA.1 variants in unvaccinated subjects previously infected, vaccinated naïve and vaccinated previously infected subjects. METHODS: Blood samples collected 15 months post-infection from unvaccinated (n=35) and vaccinated (n=41) previously infected subjects (Vo' cohort) were tested for the presence of antibodies against the SARS-CoV-2 spike (S) and nucleocapsid (N) antigens using the Abbott, DiaSorin, and Roche immunoassays. The serum neutralising reactivity was assessed against B.1, B.1.617.2 (Delta), and BA.1 (Omicron) SARS-CoV-2 strains through micro-neutralisation. The antibody titres were compared to those from previous timepoints, performed at 2- and 9-months post-infection on the same individuals. Two groups of naïve subjects were used as controls, one from the same cohort (unvaccinated n=29 and vaccinated n=20) and a group of vaccinated naïve healthcare workers (n=61). RESULTS: We report on the results of the third serosurvey run in the Vo' cohort. With respect to the 9-month time point, antibodies against the S antigen significantly decreased (P=0.0063) among unvaccinated subjects and increased (P<0.0001) in vaccinated individuals, whereas those against the N antigen decreased in the whole cohort. When compared with control groups (naïve Vo' inhabitants and naïve healthcare workers), vaccinated subjects that were previously infected had higher antibody levels (P<0.0001) than vaccinated naïve subjects. Two doses of vaccine elicited stronger anti-S antibody response than natural infection (P<0.0001). Finally, the neutralising reactivity of sera against B.1.617.2 and BA.1 was 4-fold and 16-fold lower than the reactivity observed against the original B.1 strain. CONCLUSIONS: These results confirm that vaccination induces strong antibody response in most individuals, and even stronger in previously infected subjects. Neutralising reactivity elicited by natural infection followed by vaccination is increasingly weakened by the recent emergence of VOCs. While immunity is not completely compromised, a change in vaccine development may be required going forward, to generate cross-protective pan-coronavirus immunity in the global population

Neutralising reactivity against SARS-CoV-2 Delta and Omicron variants by vaccination and infection history

Background: The continuous emergence of SARS-CoV-2 variants of concern (VOC) with immune escape properties, such as Delta (B.1.617.2) and Omicron (B.1.1.529), questions the extent of the antibody-mediated protection against the virus. Here we investigated the long-term antibody persistence in previously infected subjects and the extent of the antibody-mediated protection against B.1, B.1.617.2 and BA.1 variants in unvaccinated subjects previously infected, vaccinated naïve and vaccinated previously infected subjects. Methods: Blood samples collected 15 months post-infection from unvaccinated (n=35) and vaccinated (n=41) previously infected subjects (Vo’ cohort) were tested for the presence of antibodies against the SARS-CoV-2 spike (S) and nucleocapsid (N) antigens using the Abbott, DiaSorin, and Roche immunoassays. The serum neutralising reactivity was assessed against B.1, B.1.617.2 (Delta), and BA.1 (Omicron) SARS-CoV-2 strains through micro-neutralisation. The antibody titres were compared to those from previous timepoints, performed at 2- and 9-months post-infection on the same individuals. Two groups of naïve subjects were used as controls, one from the same cohort (unvaccinated n=29 and vaccinated n=20) and a group of vaccinated naïve healthcare workers (n=61). Results: We report on the results of the third serosurvey run in the Vo’ cohort. With respect to the 9-month time point, antibodies against the S antigen significantly decreased (P=0.0063) among unvaccinated subjects and increased (P&lt;0.0001) in vaccinated individuals, whereas those against the N antigen decreased in the whole cohort. When compared with control groups (naïve Vo’ inhabitants and naïve healthcare workers), vaccinated subjects that were previously infected had higher antibody levels (P&lt;0.0001) than vaccinated naïve subjects. Two doses of vaccine elicited stronger anti-S antibody response than natural infection (P&lt;0.0001). Finally, the neutralising reactivity of sera against B.1.617.2 and BA.1 was 4-fold and 16-fold lower than the reactivity observed against the original B.1 strain. Conclusions: These results confirm that vaccination induces strong antibody response in most individuals, and even stronger in previously infected subjects. Neutralising reactivity elicited by natural infection followed by vaccination is increasingly weakened by the recent emergence of VOCs. While immunity is not completely compromised, a change in vaccine development may be required going forward, to generate cross-protective pan-coronavirus immunity in the global population

SARS-CoV-2 antibody dynamics and transmission from community-wide serological testing in the Italian municipality of Vo’

In February and March 2020, two mass swab testing campaigns were conducted in Vo’, Italy. In May 2020, we tested 86% of the Vo’ population with three immuno-assays detecting antibodies against the spike and nucleocapsid antigens, a neutralisation assay and Polymerase Chain Reaction (PCR). Subjects testing positive to PCR in February/March or a serological assay in May were tested again in November. Here we report on the results of the analysis of the May and November surveys. We estimate a seroprevalence of 3.5% (95% Credible Interval (CrI): 2.8–4.3%) in May. In November, 98.8% (95% Confidence Interval (CI): 93.7–100.0%) of sera which tested positive in May still reacted against at least one antigen; 18.6% (95% CI: 11.0–28.5%) showed an increase of antibody or neutralisation reactivity from May. Analysis of the serostatus of the members of 1,118 households indicates a 26.0% (95% CrI: 17.2–36.9%) Susceptible-Infectious Transmission Probability. Contact tracing had limited impact on epidemic suppression

SARS-CoV-2 antibody dynamics, within-household transmission and the impact of contact tracing from community-wide serological testing in the Italian Municipality of Vo’

Background: In February and Mach 2020, two mass swab testing campaigns conducted in Vo’, Italy demonstrated the extent of asymptomatic SARS-CoV-2 infection and the feasibility of epidemic suppression. Methods: We tested 86% of the Vo’ population (2,602 subjects) in May with three immuno-assays detecting antibodies against the spike (S) and nucleocapsid (N) antigens, a neutralisation assay and Polymerase Chain Reaction (PCR). Subjects testing positive to PCR in February/March or a serological assay in May were tested again in November. Findings: Combining the results obtained with the three assays, we estimate a seroprevalence of 3.5% (95% Credible Interval (CrI) 2.8%-4.3%) in May. In November, all assays showed a reduction in antibody titres, though 98.8% (95% Confidence Interval (CI) 93.7%-100.0%) of sera still reacted against at least one antigen. Conversely, 18.6% (95% CI 11.0%-28.5%) showed a marked increase of antibody or viral neutralisation reactivity between May and November, linked to documented or likely re-exposures. We found significant differences in the magnitude and persistence of the antibody response by age group but not by symptom occurrence, hospitalisation, or sex. Analysis of the serostatus of 1,118 households indicated a 27.3% (95% CrI 19.2%-34.6%) probability of SARS-CoV-2 transmission among household members and that 81.8% (95% CrI 55.9%-95.2%) of transmission could be attributed to 20% of infections. Contact tracing correctly identified 44% of the infected subjects and had limited impact on the epidemic. Interpretation: We find evidence of antibody persistence up to nine months post infection. Different assays provided significantly different seroprevalence estimates, making it challenging to compare seroprevalence estimates globally. Due to the high population susceptibility and the limited impact of contact tracing, rigorous testing and improvements in contact tracing are essential to control SARS-CoV-2. Funding: Veneto Region, Medical Research Council, Wellcome Trust, Royal Society, University of Padua, UK National Institute for Health Research. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The first and second serosurveys of the Vo' population were approved by the Ethics Committee for Clinical Research of the province of Padova

Author Correction: SARS-CoV-2 antibody dynamics and transmission from community-wide serological testing in the Italian municipality of Vo’ (Nature Communications, (2021), 12, 1, (4383), 10.1038/s41467-021-24622-7)

The original version of this Article contained an error in the author affiliations. Affiliation 1 incorrectly read ‘MRC Centre for Global Infectious Disease Analysis and the Abdul Latif Jameel Institute for Disease and Emergency Analytics (J-IDEA), School of Public Health, Imperial College London, London, UK’ instead of the correct ‘MRC Centre for Global Infectious Disease Analysis and the Abdul Latif Jameel Institute for Disease and Emergency Analytics, School of Public Health, Imperial College London, London, UK’. The original version of this Article also contained an error in the Acknowledgements: ‘We acknowledge the Abdul Latif Jameel Institute for Disease and Emergency Analytics, funded by the Abdul Latif Jameel Foundation’ should have read ‘We acknowledge the Abdul Latif Jameel Institute for Disease and Emergency Analytics, funded by Community Jameel’. These errors have been corrected in both the PDF and HTML versions of the Article