CITF-funded findings on vaccine responses in people with compromised immune systems

Studies showed that in most immune-compromised individuals, booster doses were necessary and safe to boost much needed antibody and cell-mediated immunity levels, as their waning seems to occur faster. Here, the CITF Secretariat summarizes key data for people living with HIV, cancer, and autoimmune diseases from the four presentations given during the breakout session, “Vaccine responses in people with compromised immune systems,” at the CITF Scientific Meeting in Vancouver. March 8-10, 2023.

1. Presenter and CITF PI Dr. Matthew Oliver and CITF PI Dr. Michelle Hladunewich: Serologic response and vaccine effectiveness (VE) of a third dose of the COVID-19 mRNA vaccine in the advanced chronic kidney disease (CKD) population.

Early in the pandemic, SARS-CoV-2 infection in the maintenance dialysis population required hospitalization in 60% of cases and was associated with a 20% to 25% mortality rate. COVID-19 vaccines were prioritized in this population in Canada. The serologic response was variable in these patients and lower than in healthy controls. This study focused on determining the effectiveness of a third dose of mRNA COVID-19 vaccine in this high-risk population. 273 patients with chronic kidney diseases participated in the randomized clinical trial: 137 received a third dose of Pfizer and 136 received a third dose of Moderna. 50 from each group were tested for neutralizing antibodies.

• The third dose of an mRNA COVID-19 vaccine caused a variable but robust antibody response for most dialysis patients, although a small number did not respond.
• The third dose of Moderna vaccine produced a higher level of antibody response than the Pfizer vaccine, but differences in clinical outcomes were not demonstrated in randomized clinical trials.
• Neutralizing antibodies to wild-type, Delta, and Omicron BA.1 pseudoviruses were not significantly higher in those receiving a third dose of Moderna vaccine compared to a third dose of Pfizer vaccine.
• The third vaccine dose significantly reduced infection and severe outcomes in the dialysis population, but vaccine effectiveness was lower than with two doses of vaccine in the pre-Omicron era.
  • Case mortality in the Omicron era (4 to 6%) was substantially less than in the pre-vaccination period (26%) or pre-Omicron era with two doses of vaccine (10%).

2. Presenter Dr. Cecilia Costiniuk and CITF PI Dr. Aslam Anis: COVID-19 vaccine immunogenicity in people living with HIV (CIHR Canadian HIV Trials Network 328)

This study analyzed 1450 samples from participants living with HIV in Montreal, Ottawa, Toronto, and Vancouver. Samples were provided pre-vaccination, and after the first, second, third, and fourth doses.

• Three doses of COVID-19 mRNA vaccine were able to induce humoral and cell-mediated immunity in HIV-positive individuals, at levels similar to those of HIV-negative individuals.

3. Presenter Dr. Curtis Cooper and CITF PIs Dr. Angela M. Crawley and Dr. Marc-André Langlois: COVID-19 vaccine immunogenicity based on immune compromised status: A Stop the Spread Ottawa (SOS) analysis

The study participants included immune compromised individuals with conditions such as asthma/chronic obstructive pulmonary disease, rheumatological conditions, diabetes, localized autoimmune diseases, localized immune dysfunction, inflammatory conditions, cancer, HIV, and organ transplants.

• COVID-19 vaccines were safe and well tolerated in immune-compromised individuals.
• COVID-19 vaccines were highly immunogenic across a broad spectrum of vaccine recipients, including those with a range of immune compromising conditions.
• In immunocompromised individuals with no history of SARS-CoV-2 infection, mRNA vaccines worked better than vector-based vaccines.

4. Presenter and CITF PI Dr. C. Arianne Buchan: COVID-19 immunogenicity surrounding fourth vaccine dose in patients with hematologic malignancies: A prospective real-world observational multi-site Canadian study

240 participants with Chronic Lymphocytic Leukemia (CLL), lymphoma, myeloid leukemia, or Plasma Cell Disorders (PCD) were recruited for the study. The median age of participants was 66.5 years, and 49% were male. 30% of participants also had a history of exposure to anti-CD20 agents that promote tumor cell death.

• Humoral immune response (measured by anti-S levels) improved after the fourth dose. 26% of participants with a negative anti-S level developed a positive anti-S result after the fourth dose.
• Humoral immune responses decreased during the period after the third dose to before the fourth dose, and increased again after the fourth dose.
• Participants exposed to an anti-CD20 agent were less likely to have a positive anti-S antibody level after the fourth dose than those not exposed to those treatments.