SARS-CoV-2 humoral, cellular immunity in people with cancer characterized
medwireNews: Two papers from the prospective, longitudinal UK CAPTURE consortium shed light on the humoral and cellular immune response to SARS-CoV-2 vaccination and infection in patients with cancer.
Both articles are published in Nature Cancer and focus on functionally relevant neutralizing antibody (Nab) and T cell responses against SARS-CoV-2, including emerging variants of concern (VOC), with one looking at these responses in cancer patients who have undergone COVID-19 vaccination and the other in unvaccinated patients who acquired the infection.
The vaccine cohort results
Samra Turajlic, from The Francis Crick Institute in London, UK, and collaborators report on 585 patients with cancer who received at least one dose of the Oxford–AstraZeneca (ChAdOx1 nCoV-2019) or Pfizer–BioNTech (BNT162b2) vaccine between May 2020 and June 2021, with the majority (93%) receiving two doses at a median of 77 days apart.
Patients were aged a median of 60 years, 60% were men, and just over three-quarters (76%) had a solid tumor, while the remaining 24% had a hematologic malignancy. Thirty-one percent had prior SARS-CoV-2 infection, based on either a positive RT-PCR or antibody test.
The researchers used a high-throughput live virus-neutralization assay and found that 49% of the infection-naïve participants had detectable NAbs against the wild-type strain, with significantly lower rates of detectable NAbs against the Alpha, Beta, and Delta VOC, at 15%, 9%, and 9%, respectively.
The proportion of participants with detectable NAbs against all strains rose after the second dose, but to a greater degree for the wild-type strain, at 83%, than for the VOC, at 61% for Alpha, 53% for Beta, and 54% for Delta.
Among patients with prior infection, the proportion with NAbs against the wild-type strain increased from 62% at intake to 85% after the first dose of vaccine and 95% after the second dose. The corresponding rates for the Alpha variant were 52%, 65%, and 88%, while they were 39%, 61%, and 80% for the Beta variant and 41%, 59%, and 80% for Delta.
Of concern, NAb positivity against all strains was lower for people with hematologic malignancies than those with solid tumors. For instance, the proportion of infection-naïve solid tumor patients with NAbs against the wild-type, Alpha, Beta, and Delta strains after the second dose were 92%, 70%, 61%, and 62%, respectively, while among hematologic cancer patients, the rates were a respective 56%, 35%, 28%, and 31%.
In both groups, the NAb positivity rates were higher among those with than without prior COVID-19, “although, again, values were lower for those with hematological malignancies than for those with solid cancers,” comment the researchers.
They also evaluated spike (S) protein-specific T cell responses using the interferon-γ enzyme-linked immunospot (ELISpot) after stimulation with wild-type S peptide pools in a subset of 324 participants, 86% of whom had a solid tumor.
A detectable T cell response to the wild-type strain was observed in 44% of infection-naïve patients after the first vaccine dose and in 79% after the second dose. Thirty-two percent of patients with prior infection had a T cell response at baseline, rising to 69% and 87% after the first and second dose, respectively.
The investigators highlight that there was no significant difference in the rates of T cell responses between the solid and hematologic cancer infection-naïve patients either after the first (45 vs 34%) or second (78 vs 83%) dose.
They additionally point out that T cell responses occurred in some patients without detectable NAbs and also against Alpha and Delta peptide pools, “in agreement with a recent report suggesting that T cells induced by [wild-type] SARS-CoV-2 were effective against VOC.”
The team continues: “Overall, however, our understanding of the role of T cells in immune protection from SARS-CoV-2 remains incomplete; while they are not expected to prevent infection, T cell responses are likely to reduce COVID-19 severity.”
Turajlic and colleagues believe these findings “have clear implications for the management of patients with cancer,” and conclude: “Our data support the prioritization of patients with cancer for booster vaccine doses, suggesting that the highest priority should be given to those with hematological malignancies.”
The infection cohort data
The second analysis, also by Turajlic and team, included 118 patients with cancer – 82% with a solid tumor and 18% with a hematologic malignancy – who tested positive for SARS-CoV-2 on the basis of an RT-PCR or antibody test. Participants were aged a median of 60 years and 54% were men
“[O]ur cohort consisted mainly of convalescent patients with a range of COVID-19 presentations, from asymptomatic to severe disease,” note the researchers.
Specifically, 20% of the cohort was asymptomatic, whereas a respective 44%, 31%, and 5% had mild, moderate, or severe disease as per the WHO severity index. Twenty-eight percent of patients required hospitalization, 23% supplemental oxygen, 6% intensive care, and 2% died due to COVID-19-related complications.
Among the evaluable 112 patients, who had acquired either the wild-type SARS-CoV-2 strain (n=85) or the Alpha variant (n=27), a significantly greater proportion had detectable NAbs against the wild-type virus than the Alpha, Beta, or Delta VOC, at 82% versus 79%, 69%, and 65%, respectively.
This finding “raises concerns about the protection afforded by natural immunity to new SARS-CoV-2 VOCs,” says the team.
“Whether such responses can be boosted by COVID-19 vaccines remains under investigation in the vaccine cohort of our study, which includes the currently predominant Delta VOC.”
Similar to the vaccine cohort, the study authors found that “[t]he proportion of patients with detectable NAbs against all variants was significantly lower in patients with hematological malignancies than in those with solid cancer,” with rates of 65% versus 86% for the wild-type virus, 60% versus 84% for the Alpha VOC, 45% versus 74% for Beta, and 40% versus 71% for Delta.
And multivariate binary logistic regression analysis showed a significant association between hematologic malignancy and undetectable NAbs.
Turajlic et al also looked at the duration of antibody response, finding that titers of S1-reactive antibodies demonstrated “a weak declining trend” during follow-up, with 24% of 59 participants becoming seronegative at a median of 24–313 days after onset of COVID-19. By contrast, NAb titers “remained stable” until day 336, and NAbs against the wild-type strain were detected in 71% of the patients who became seronegative, they report.
Finally, the team assessed SARS-CoV-2-specific CD4+ and CD8+ T cells at a median of 59 days after disease onset. CD4+ cells were detected in 77% of 100 evaluable patients, with rates of 81% and 58% in those with solid or hematologic malignancies, respectively, while the corresponding rates for CD8+ cells were 49%, 51%, and 42%.
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