CITF-funded findings on immune responses to SARS-CoV-2 variants and hybrid immunity

CITF-funded studies continue to monitor immune responses to SARS-CoV-2 variants and increases in hybrid immunity among Canadians. Here, we summarize results from the four presentations given during the breakout session “Immune responses to SARS-CoV-2 variants and hybrid immunity” at the CITF Scientific Meeting in Vancouver, March 8-10, 2023. These findings on the strength and durability of immunity (whether hybrid, infection-acquired, or vaccine-induced) help to better inform public policy and recommendations for Canadians.

1. Presenter Dr. Kayla Holder and CITF PI Dr. Michael Grant: Hybrid immunity against SARS-CoV-2 elicits cross-variant ADCC

Humoral (antibody-mediated) immunity induced by SARS-CoV-2 ancestral strains does not completely neutralize variant strains. Another mechanism called antibody-dependent cell-mediated cytotoxicity (ADCC) allows for targeted cell killing. This study examines the immune responses in individuals who were both infected and vaccinated, known as hybrid immunity, versus those vaccinated only.

• Individuals with hybrid immunity (had a previous SARS-CoV-2 infection and received one or two vaccines) generate high levels of antibodies against S1 and S2 subunits of SARS-CoV-2.
• There is greater ADCC after SARS-CoV-2 infection and one vaccination than after two vaccinations only. A high ADCC response also mirrors high full-length SARS-CoV-2 spike IgG antibody levels.
• Individuals with hybrid immunity induce ADCC against ancestral SARS-CoV-2 strains, which is also effective against Omicron.

2. Presenter Dr. Mariana Baz and CITF PI Dr. Denis Boudreau: Live virus neutralizing antibodies against ancestral SARS-CoV-2, Delta, BA.1, BA.2, BA.2.12.1, BA.4, and BA.5 strains in food and retail workers in Québec, Canada

Neutralizing antibodies are important for virus clearance and are a major determinant of protection from infection in humans. This study involved studying neutralizing antibody levels in retail workers in Quebec who were vaccinated or who were vaccinated and infected (in whichever order). Various SARS-CoV-2 strains were analyzed.

• Neutralizing antibody concentrations against ancestral SARS-CoV-2 and the Delta variant were similar. The neutralizing antibody concentrations decreased for other variants including BA.1, BA.2, BA.2.12.1, BA.4 and BA.5.
• Similar patterns of neutralizing antibody concentrations were observed in terms of sex, age, weight (body mass index above and below 30), chronic diseases, and whether participants smoked or vaped.
• Individuals who were both vaccinated and infected had better neutralizing antibody concentrations than individuals who were vaccinated with two doses but never infected. Individuals vaccinated with two to three doses of vaccine and then infected had consistently higher neutralizing antibody concentrations against all variants.
• Individuals who were vaccinated with two doses of Moderna had higher neutralizing antibody titers against the ancestral SARS-CoV-2 strain than those who received AstraZeneca/Pfizer or AstraZeneca/Moderna.
• Individuals who had received two doses of Moderna, two doses of Pfizer, and three doses of Pfizer had higher neutralizing antibody titers against the Delta variant than AstraZeneca/Pfizer or AstraZeneca/Moderna.

3. Presenter and CITF PI Dr. Jen Gommerman: Omicron breakthrough infection induces superior mucosal and humoral immunity to SARS-CoV-2 variants than booster vaccination

Both mucosal and humoral immunity contribute to the overall immune response to SARS-CoV-2. Assessment of mucosal immunity involves measuring antibodies in saliva, which have been found to correlate with antibodies in the blood. This study examines the immune responses in people with breakthrough infections versus those with vaccination only.

• A second mRNA vaccine dose induced a weak, transient, and variable mucosal IgA antibody response in saliva that declines in most people. In contrast, IgG (the most common protein found in the blood) increased after the second vaccine dose.
• People with breakthrough infections (infection after vaccination) had lower levels of serum and mucosal anti-spike IgA.
• Individuals with two vaccine doses and a breakthrough Omicron infection had higher neutralizing antibodies against different SARS-CoV-2 variants compared to individuals with two or three vaccine doses only.
• Individuals with Omicron breakthrough infections had increased spike IgG and IgA salivary antibodies to the Omicron variant compared to individuals with two or three vaccine doses who had no infection.
• Individuals with Omicron breakthrough infections had increased anti-spike IgA to the ancestral Wuhan SARS-CoV-2 and SARS-1 variants compared to individuals with two or three vaccine doses who had no infection.

4. Presenter and CITF PI Dr. Tania Watts: Lessons learned from monitoring T cell responses to SARS-CoV-2 infection and vaccination

T cells are an important part of the immune response, working along with antibodies to respond effectively to SARS-CoV-2 infection. Both cellular and humoral Immune responses after COVID-19 vaccination were assessed in individuals with immune-mediated inflammatory diseases (IMID), some of whom were on anti-TNF therapies.

• The most predominant cytokine Small proteins that help in cell-to-cell communication in immune responses in the SARS-CoV-2 response was IL-2 produced by T cells in patients with mild COVID-19. This persisted up to nine months post-symptom onset. In hospitalized patients, the predominant cytokine was TNF produced by TNF-producing cells.
• The SARS-CoV-2 spike specific response was dominated by a strong CD4 and a weak CD8 response.
• The third vaccine dose reduced waning of immunity. It was critical for neutralizing variants of concern in IMID patients being treated with anti-TNF.
• The fourth vaccine dose was found to maintain antibody and neutralization responses up to three months post vaccination. It also increased T cell IL-4 production in the anti-TNF/combination treatment group.