This is a summary, written by members of the CITF Secretariat, of:

Mwimanzi, F., Lapointe HR, Cheung PK, Sang Y, Yaseen F, Umviligihozo G, Kalikawe R, Datwani S, Omondi FH, Burns L, Young L, Leung V, Agafitei O, Ennis S, Dong W, Basra S, Lim LY, Ng K, Pantophlet R, Brumme CJ, Montaner JSG, Prystajecky N, Lowe CF, DeMarco ML, Holmes DT, Simons J, Niikura M, Romney MG, Brumme ZL, and Brockman MA (2022). Older adults mount less durable humoral responses to two doses of COVID-19 mRNA vaccine, but strong initial responses to a third dose. J Infect Dis; jiac199. doi: 10.1093/infdis/jiac199.

The results and/or conclusions contained in the research do not necessarily reflect the views of all CITF members.

While two doses of the COVID-19 vaccine can prevent serious illness in most cases, vaccine-induced immune responses decline naturally over time, increasing the risk of breakthrough infections. A paper from CITF-funded researchers Dr. Mark Brockman of Simon Fraser University, Dr. Zabrina Brumme of Simon Fraser University and the BC Centre for Excellence in HIV/AIDS, and Dr. Marc Romney, from Providence Health Care and the University of British Columbia, published in the Journal of Infectious Diseases showed that a third dose of COVID-19 vaccine elevated both the levels of antibodies and their neutralizing capacity above that of two doses in all individuals, including older adults. The research team also shows that a third dose stimulates stronger responses against the Omicron variant than that which was seen after two doses.

Key Points:

  • After two doses of mRNA vaccines, binding antibody responses decline fastest among older adults and those with a higher burden of chronic conditions.
  • Upon receiving a third dose booster, older adults mount antibody responses similar to what is seen in a cohort of younger healthcare workers (HCW). Following a third dose, a higher number of chronic health conditions was the sole significant correlate of lower antibody concentrations between the two groups.
  • After two doses of mRNA vaccination, neutralizing antibodies against the wild-type virus were significantly higher in HCW compared to older adults. Neutralizing activity had declined to below the limit of quantification in at least 83% of older adults in comparison to 58% of HCW at six months post-second dose. A third vaccine dose boosted the neutralizing activity in HCW and older adults two and eight times higher, respectively, than the peak responses after two doses.
  • IgG antibodies against the Omicron variant’s receptor-binding domain (RBD) after two or three vaccine doses were lower than against wild-type RBD antigens after two and three doses. Nevertheless, the third dose boosted anti-Omicron IgG antibody concentrations more robustly than the levels induced by two doses within all groups.
  • Similar to IgG response, all the groups showed significantly lower neutralizing capabilities against Omicron when compared to the wild-type virus. Neutralizing antibodies capable of blocking Omicron followed a similar pattern, with HCW showing marginally higher anti-Omicron IgG levels compared to older adults after two doses, but equivalent levels after three.
  • Individuals with prior COVID-19 infections who received two doses of vaccine had higher antibody levels than both HCW and older adults six months post-second vaccine dose who were not previously infected.
  • A longer dose interval was also associated with higher antibody concentrations at all time points after the second dose.

The cohort included 81 healthcare workers (HCW), 56 older adults (including 18 residents of long-term care or assisted living facilities), and 14 individuals with prior COVID-19 infection (including 8 HCW and 6 older adults) who received two doses of mRNA vaccination. At study entry, the median age of these groups was 41, 79 and 48 years, respectively. The older adults had a higher burden of chronic health conditions. All participants received two COVID-19 mRNA vaccine doses and the dosing interval was up to 112 days. 114 participants received a third dose booster (32 HCW, 19 older adults and 3 individuals with prior COVID-19 infections), on average seven months after the second dose.

The evidence supports the importance of booster doses for both younger and older adults. Older adults and people with pre-existing medical conditions should continue to be prioritized, as these groups receive particularly significant immune benefits from a third dose.