Pillar 1
Immunology & Vaccine Protection

Booster doses of COVID-19 mRNA vaccine are widely recommended to maintain immunity against SARS-CoV-2, but longer-term studies of vaccine-induced responses remain limited, particularly among older adults and individuals who have experienced an Omicron breakthrough infection following vaccination.

This study of 116 adults, which is available as a pre-print and not yet peer-reviewed, demonstrates that a third dose of mRNA vaccine significantly enhances the magnitude of SARS-CoV-2-specific antibody responses among adults who remained naive to viral infection. While antiviral IgG concentrations in blood were similar between younger and older adults, the responses against Omicron variants were consistently significantly lower compared to those against the ancestral (Wuhan) strain. Virus neutralization activity declined substantially over time post-vaccination and Omicron-specific neutralization activity was below the limit of detection in most participants (56% of younger adults and 96% of older adults) at six months following the third mRNA vaccine dose.  In a subset of 38 adults who experienced a presumed Omicron infection after receiving three vaccine doses, the resulting “hybrid” immune response featured elevated IgG concentrations and virus neutralization activities against ancestral and Omicron strains compared to vaccination alone; however, responses against Omicron strains remained significantly lower compared to those against the ancestral strain.

The findings of this study reinforce the immune benefits of a third vaccine dose and further suggest that COVID-19 naive individuals, particularly older adults, may require fourth doses within three to six months after receiving their third to maintain protection against Omicron strains. By contrast, individuals who have contracted SARS-CoV-2 infection after receiving three vaccine doses may derive less benefit from a fourth dose within this timeframe. Overall lower antiviral activity against Omicron strains indicates that most individuals will remain at higher risk of infection by Omicron variants despite booster vaccination and perhaps even after a breakthrough infection.

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Francis Mwimanzi, Hope Lapointe, Peter Cheung, Yurou Sang, Fatima Yaseen, Rebecca Kalikawe, Sneha Datwani, Laura Burns, Landon Young, Victor Leung, Siobhan Ennis, Chanson Brumme, Julio Montaner, Winnie Dong, Natalie Prystajecky, Christopher Lowe, Mari DeMarco, Daniel Holmes, Janet Simons, Masahiro Niikura, Marc Romeny, Zabrina Brumme, Mark Brockman. Impact of age and SARS-CoV-2 breakthrough infection on humoral immune responses after three doses of COVID-19 mRNA vaccine. medRxiv. 2022.08.08.22278494; https://www.medrxiv.org/content/10.1101/2022.08.08.22278494v1