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

Abstract

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.

Trajectories of Seroprevalence and Neutralizing Activity of Antibodies against SARS-CoV-2 in Southern Switzerland between July 2020 and July 2021: An Ongoing, Prospective Population-Based Cohort Study

“…Furthermore, our observations on the inverse association of the proportion of samples that could efficiently neutralize spike proteins with increasing viral mutations after two doses of a vaccine and before the circulation of the Omicron (B.1.1.529) variant extend preliminary findings obtained in mechanistic studies [ 35 ] and in selected clinical samples [ 60 , 61 ]. Similar to findings recently reported [ 19 , 21 , 24 , 25 , 62 , 63 , 64 , 65 ], neutralizing antibody titers were higher in the vaccinated than in the non-vaccinated individuals.…”

Development of hybrid immunity during a period of high incidence of infections with Omicron subvariants: A prospective population based multi-region cohort study

“…These findings are in line with previous studies, conducted in small and non-population-based samples, showing that hybrid immunity can confer to antibodies a better neutralisation capacity. [24][25][26][27][28][29][30] This study is the first to demonstrate the extent of hybrid immunity and neutralisation capacity in the general population in 2022. It is likely that we underestimated hybrid immunity and that its prevalence is higher than 51%, as anti-nucleocapsid antibodies wane quickly and we likely missed some infections that occurred before 2022.…”

Antibody Response after SARS-CoV-2 Infection with the Delta and Omicron Variant

“…Several factors play a role in vaccines’ effectiveness; the difference in the heterogeneity of the immunized population, virus mutation, and the dominancy of a new variant of concern (VOC) which can decrease vaccine effectiveness [ 19 ]. Moreover, breakthrough infections demonstrate reduced vaccine effectiveness against B.1.617.2 [ 20 , 21 , 22 , 23 ].…”