Pillar 1
Immunology & Vaccine Protection

COVID-19 mRNA vaccines have provided significant protection against SARS-CoV-2 infection and disease, particularly among older adults who are at highest risk of severe illness. While two vaccine doses may be effective initially, vaccine-induced immune responses in blood decline naturally over time and this is associated with an increased risk of breakthrough viral infection.  Third booster doses are now recommended for most individuals to maintain antiviral protection, but few reports have examined the durability of vaccine-induced immune responses in older adults or the impact of third booster doses on responses against the Omicron variant.

This study of 151 individuals, published in The Journal of Infectious Diseases, demonstrates that antiviral antibody responses in blood were significantly lower among older adults compared to younger adults after two vaccine doses. Older adults also displayed a faster rate of antibody decline in blood, which was attributed to a higher number of chronic health conditions in this group rather than older age per se.  Furthermore, virus neutralization activities against the ancestral (Wuhan) and Omicron BA.1 strains were significantly lower among older adults, most of which (85%) displayed no ability to neutralize Omicron. Following a third vaccine dose, antiviral antibody levels increased significantly in both groups and reached equivalence between younger and older adults. Moreover, a third vaccine dose significantly enhanced virus neutralization activity against the ancestral and Omicron BA.1 strains, which also reached equivalence between younger and older adults.

The findings of this study illustrate the immune benefits of a third mRNA vaccine dose, particularly among older adults who typically displayed weaker antiviral antibody responses and virus neutralization activities after two doses.  Importantly, a third vaccine dose was crucial to stimulate virus neutralization activity against the Omicron BA.1 variant in older adults, although Omicron-specific responses were substantially lower than those against the ancestral strain in both younger and older adults, and their effectiveness to prevent Omicron infection is uncertain.

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Francis Mwimanzi, Hope Lapointe, Peter Cheung, Yurou Sang, Fatima Yaseen, Gisele Umviligihozo, Rebecca Kalikawe, Sneha Datwani, Harrison Omondi, Laura Burns, Landon Young, Victor Leung, Olga Agafitei, Siobhan Ennis, Winnie Dong, Simon Basra, Li-Yi Yim, Kurtis Ng, Ralph Pantophlet, Chanson Brumme, Julio Montaner, Natalie Prystajecky, Christopher Lowe, Mari DeMarco, Daniel Holmes, Janet Simons, Masahiro Niikura, Marc Romney, Zabrina Brumme, Mark Brockman. Older adults mount less durable humoral responses to two doses of COVID-19 mRNA vaccine but strong initial responses to a third dose. The Journal of Infectious Diseases. 2022.09.15.6583561; https://academic.oup.com/jid/article/226/6/983/6583561