Omicron neutralizing antibody response following booster vaccination compared with breakthrough infection

Abstract

The rapid spread of the vaccine-resistant Omicron variant of SARS-CoV-2 presents a renewed threat to both unvaccinated and fully vaccinated individuals, and accelerated booster vaccination campaigns are underway to mitigate the ongoing wave of Omicron cases. The degree of immunity provided by standard vaccine regimens, boosted regimens, and immune responses elicited by the combination of vaccination and natural infection remain incompletely understood. The relative magnitude, quality and durability of serological responses, and the likelihood of neutralizing protection against future SARS-CoV-2 variants following these modes of exposure are unknown but are critical to the future trajectory of the COVID-19 pandemic. In this study of 99 vaccinated adults, we find that compared with responses after two doses of an mRNA regimen, the immune responses three months after a third vaccine dose and one month after breakthrough infection due to prior variants show dramatic increases in magnitude, potency, and breadth, including increased antibody dependent cellular phagocytosis and robust neutralization of the recently circulating Omicron variant. These results suggest that as the number of Omicron cases rise and as global vaccination and booster campaigns continue, an increasing proportion of the population of the world will acquire potent immune responses that may be protective against future SARS-CoV-2 variants.

Impact of age and SARS-CoV-2 breakthrough infection on humoral immune responses after three doses of COVID-19 mRNA vaccine

“…By contrast, both younger and older adults who experienced their first SARS-CoV-2 infection (presumably Omicron BA.1 or BA.2 [12]) after three-dose vaccination demonstrated superior binding and functional humoral responses to those induced by triple-vaccination alone. This is consistent with other studies of hybrid immunity [10, 14, 15] and suggests that a post-third-dose infection may provide prolonged immune protection. The observation that immune enhancement was most pronounced for Omicron-specific responses ( e.g .…”

Serial infection with SARS-CoV-2 Omicron BA.1 and BA.2 following three-dose COVID-19 vaccination

“…The observation that average humoral responses to three-dose vaccination failed to protect the participant against Omicron BA.1 infection is consistent with the extremely high rates of community transmission observed in many regions during recent Omicron-driven pandemic waves. Given that third vaccine doses substantially boost humoral responses in individuals of all ages ( 30 – 33 ), the relative risk of Omicron breakthrough infection is likely to be even higher among individuals who have received fewer than three doses ( 18 , 34 ). Relative risk is also likely to increase with time following vaccination due to natural declines in antibody responses ( 26 , 35 – 38 ), which, combined with natural Spike antigenic drift, may lead to ongoing risk of periodic re-infection ( 39 ).…”

Protection from Omicron and other VOCs by Bivalent S-Trimer COVID-19 Vaccine

“…Therefore, we designed a bivalent vaccine, to address advanced models that attempt to define the antigenic range of SARS-CoV-2 (20) by selecting our Ancestor vaccine, SCB-2019, which occupies a centroid range of antigenicity and has shown high levels of efficacy against VOCs in a phase 3 trial (10), and the Omicron strain given its divergent antigenicity and its global prevalence. This approach is supported by the observation that individuals who have received two doses of Ancestor vaccine and subsequently infected with Omicron have high levels of broad cross-reactive neutralization against panels of VOCs (21). An Omicron only monovalent vaccine, while likely to elicit protection against Omicron and related sub-lineages, is however potentially ineffective against other VOC distal from its antigenic position; a rationale for bivalency to mitigate this risk.…”