This evidence review was compiled by members of the CITF Secretariat with the input from experts affiliated with the CITF and does not necessarily reflect the views of all CITF members.

Kristin Davis, Research Assistant, CITF Secretariat
Bruce Mazer, Associate Scientific Director – Strategy, CITF Secretariat

With the arrival of Omicron and the looming threat of other variants to come, the question on everyone’s mind is: how long does immunity to SARS-CoV-2 last? Protection from SARS-CoV-2 infection and the disease it causes (COVID-19) cannot be fully understood without concrete “real-world” data on immunity and recurrence. Because SARS-CoV-2 is still a relatively new virus, the duration of immunity is a very active research question. Data are being collected and analyzed in real-time. CITF experts are among those grappling with this issue and we offer a current overview from around the world of where the science stands to date.

Immune memory: An overview

Recovery from a viral infection is typically followed by a period of immunological memory. After fighting the infection, antibody-producing B-cells enter a dormant state known as ‘memory’ B-cells. These linger in the body, patiently awaiting their next confrontation with the virus against which they were primed. T-cells also become dormant, remembering the viral intruder, ready to mount a swift immune response and directly kill virus-infected cells in any future encounters.

This is the basis underlying vaccination: the immune system is exposed to a harmless protein fragment of a virus. This activates an immune response to make antibodies and T-cells for future exposures to the virus.

Normally, if not called upon, antibodies fade over a period of months to years. Immunity acquired to some viruses, including influenza and the seasonal coronaviruses causing the common cold, also diminishes because the virus’ genetic evolution helps them evade pre-programmed immune responses (1-3). As a result, most immunization schedules include additional doses of vaccine, called boosters. As their name suggests, boosters, administered sometime after the first or ‘primer’ doses, help to stimulate the immune system through re-exposure. Memory B-cells and T-cells are called into action and fine-tune their immune responses in a manner that is more long-lasting. Hence, boosters help by elevating immunity to the same level as, or higher than, the first exposure.

Why do we need boosters for COVID-19?

Part one: Waning immunity

In the months since most Canadians received their last vaccine dose, immunity has most likely declined. Thus, they need re-exposure: a booster is the ideal way.

  1. Breakthrough infections more frequent months after vaccination
    Research emerging from Israel comparing individuals 60 years and older who received a third shot of Pfizer-BioNTech’s Comirnaty vaccine to those who had received only two doses found that the third shot made people 11 times less likely to acquire a breakthrough infection and 20 times less likely to become severely ill from COVID-19 (4). Recent preprints (not yet peer-reviewed) have demonstrated that a third dose of an mRNA vaccine could significantly increase vaccine effectiveness against both the Delta and Omicron variants (5,6). These studies offer preliminary evidence indicating that a booster helps address waning immunity, especially against emerging variants.
  2. Antibody levels decline over time
    Data are currently insufficient to define a measurable unit of immunity, known as a correlate of protection, that indicates whether an individual is protected from infection. However, we do know that the mean peak of neutralizing (that is to say, virus-blocking) antibody titers and anti-SARS-CoV-2 spike antibodies is strongly correlated with a lower risk of infection (7,8). Multiple studies supported by Canada’s COVID-19 Immunity Task Force (CITF) have shown that antibodies against SARS-CoV-2 diminish significantly with time since infection and/or vaccination (9-15).

Part two: Immune evasion

As genetic modifications help viruses evade built-up immunity, it is not surprising that highly mutated strains of SARS-CoV-2, such as Omicron, will cause more reinfections and breakthrough infections. Indeed, recent and not yet peer-reviewed studies have found reinfection rates to be at least three times higher with Omicron as compared to Delta (16,17). Not only has Omicron emerged at a time when swaths of the population had waning immunity to SARS-CoV-2, but its constellation of mutations has also allowed it to escape existing immunity.

An additional vaccine dose is more effective when faced with highly mutated variants

Two reports released in preprint from Australia and Israel have demonstrated that a third dose of the Pfizer-BioNTech vaccine significantly increases neutralizing antibodies recognizing the original strain of SARS-CoV-2, as well as the Delta and Omicron variants (18,19). Moreover, a growing body of evidence suggests that, while antibodies to the original strain of SARS-CoV-2 are less specific to variants, higher levels of these antibodies can still be effective in countering infection (20,21). Since boosters help to elevate the level of antibodies, including neutralizing antibodies, they are particularly helpful in the context of emerging variants. Therefore, the possibility of immune evasion is the second reason behind the pressing need for boosters in the Canadian population.

Further to this, CITF research has confirmed that virus-specific T-cells persist at least nine months after first exposure (21). In contrast to what we see with antibodies, T-cells may still easily recognize the heavily mutated Omicron SARS-CoV-2 virus (23,24).

CITF research on durability

The CITF supports several research projects striving to understand the duration of immunity to SARS-CoV-2. Studies of older Canadians (such as residents in long-term care homes) and of those at higher risk of illness due to underlying health conditions (such as those who are immunocompromised) have pivoted to monitor the added benefit of a third dose (25-27). Booster doses have been administered following recommendations from the National Advisory Committee on Immunization in October 2021 in these more vulnerable populations.

Additionally, the Canadian Immunization Research Network (CIRN) Provincial Collaborative Network (PCN), funded in part by the CITF, has released reports of the effectiveness of two vaccine doses against symptomatic SARS-CoV-2 infection and severe outcomes (28,29). Indeed, this network has already started to monitor the incidence and severity of breakthrough infections in the Omicron-fuelled era (6).

Beyond its multiple population-based studies, the CITF also supports several studies focused on immune science and testing. Information stemming from these studies has been instrumental in understanding the depth, breadth, and persistence of immune responses to COVID-19 infection and vaccination (14,15,22, 30-32).

Conclusion

The best protection against SARS-CoV-2 comes from vaccination. Being optimally protected includes receiving a booster when it becomes available – even for those previously infected – while continuing to follow local public health measures. With Omicron’s mutations and increased transmissibility, a booster has become essential, even in vaccinated and otherwise healthy adults. Despite our current vaccines having been developed with the original SARS-CoV-2 strain in mind, early studies from various parts of the world have all concluded that a booster provides additional protection against the highly mutated Omicron.

References

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  2. Eguia RT, Crawford KHD, Stevens-Ayers T, Kelnhofer-Millevolte L, Greninger AL, Englund JA, et al. A human coronavirus evolves antigenically to escape antibody immunity. PLoS Pathog. 2021;17(4):e1009453.
  3. Edridge AWD, Kaczorowska J, Hoste ACR, Bakker M, Klein M, Loens K, et al. Seasonal coronavirus protective immunity is short-lasting. Nat Med. 2020;26(11):1691-3.
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  25. Zhang A, Breznik JA, Clare R, Nazy I, Miller MS, Bowdish DME, et al. Antibody Responses to 3rd Dose mRNA Vaccines in Nursing Home and Assisted Living Residents. medRxiv. 2021.
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