The group designated in Saskatchewan as Clinically Extremely Vulnerable (CEV) is a heterogenous clinical population with factors that impair their immune response to differing degrees.
Very Limited evidence is currently available to assess the immune response following vaccination is selected clinical populations; no evidence is available to assess vaccine efficacy or effectiveness in these populations. The clinical relevance of measured immune response with respect to protection from disease is still uncertain.
In considering the immune response of the CEV population, it is recommended that the absolute difference in immune response between 1 and 2 doses be considered, as it is possible some patient groups will have lowered protection regardless of vaccine strategy.
In terms of clinical subgroups:
oOrgan transplantation recipients on immunosuppressive medication: solid organ transplant recipients receiving anti-metabolite maintenance immunosuppression therapy were less likely to develop an antibody response to an mRNA vaccine, compared to those receiving other types of therapies (37% vs 63%). In a study of 242 kidney transplant recipients on immunosuppressive therapy only 10.8% became seropositive at 28 days after a single dose of mRNA vaccine.
oCancer: A study of 151 elderly patients with solid and hematological malignancies and 54 healthy controls who received one or two doses of BNT162b2 (Pfizer-BioNTech) vaccine shows approximately 39% of solid cancer patients, 13% of hematological cancer patients, and 97% of healthy controls (p<0.0001) developed anti-S IgG 21 days following a single dose vaccine. However, response in solid cancer patients increased to 95% within 2 weeks of the second dose at 21 days.
oOther immunocompromising conditions (e.g., auto-immune disorders and therapy): some level of immunity is generated with vaccination; however, what this means clinically is unknown. It seems that ensuring the dosing is properly timed around biologic therapy is important.
Azizian, A; Lee, S; Shumilak, G; Groot, G; Reeder, B; Miller, L; Howell-Spooner, B. What are the risks or benefits of extended intervals between doses of COVID-19 vaccines compared to recommended dosing in extremely vulnerable populations? 2021 Apr 20, Document no.: EOC210302 RR. In: COVID-19 Rapid Evidence Reviews [Internet]. SK: SK COVID Evidence Support Team, c2021. 15 p. (CEST rapid review report).
Emerging evidence suggesting waning levels of immune markers with time, particularly against more virulent variants. How this will correlate to functional immunity is yet to be documented.
Immunocompromised populations with lower levels of responses to standard 2-dose regimens may benefit from a 3rd dose of mRNA vaccine as a part of the primary series, though their response may still be lower than what is expected in the general population
Current recommendation for populations to receive a 3rd dose include adults over a certain age (depending on jurisdiction), those living in long-term care settings, frontline health and social workers and/or people working in high risk settings, those with immune compromising conditions leading to increased risk of severe disease/poor outcomes if infected
Safety trials have indicated that side effects to 3rd/booster doses are similar to those following the 2nd dose in initial vaccination series
Badea, A; Groot, G; Muhajarine, N; Lee, S; Shumilak, G; Hernandez-Ronquillo, L; Tian, K. What is the current evidence and recommendations regarding COVID-19 vaccine booster shots (exceeding 2 doses) for the general population? 2021 Oct 07, Document no.: EOC210902 RR. In: COVID-19 Rapid Evidence Reviews [Internet]. SK: SK COVID Evidence Support Team, c2021. 8 p. (CEST rapid review report).
Novavax was authorized for use in Canada February 16, 2022 and has also been authorized for use in 35 other countries as a 2-dose primary series given as an intramuscular injection, 21 days apart
Phase 3 trials of Novavax in US/Mexico and UK showed an overall vaccine effectiveness of 89.7-90.4% against all severity COVID infection and 100% against moderate/severe infection and death
In the US/Mexico, vaccine effectiveness against the dominant Alpha variant was found to be 92.6%, while in the UK, it’s effectiveness dropped to 86.3%
The most frequently reported local and systemic adverse events in both trials were tenderness and pain at the injection site and headache, myalgia and fatigue, respectively. Adverse events were mild-to-moderate and transient in nature, and more frequently reported following the second dose
A Phase 2 trial assessing safety and efficacy of Novavax in South Africa in adults 18-64 years during Beta dominance found a vaccine efficacy of only 49.4%, however, in subgroup analysis of only HIV negative individuals, efficacy rose to 60.1% overall, and 51% against the Beta variant. (). While efficacy against disease severity was not measured, the majority of infections reported in both the vaccine and placebo group were mild to moderate
Badea, A; Groot, G; Reeder, B; Miller, L. What is the safety/efficacy of the Novavax COVID-19 vaccine? 2022 Mar 10. Document no.: EOC220302 RR. In: COVID-19 Rapid Evidence Reviews [Internet]. SK: SK COVID Evidence Support Team, c2022. 7 p. (CEST rapid review report).