Immune checkpoint inhibitors increase T cell immunity during SARS-CoV-2 infection

Yatim, Nader; Boussier, Jérémy; Tétu, P.; Smith, Nikaïa; Bruel, Timothée; Charbit, Bruno; Barnabei, Laura; Corneau, Aurélien; Meda, Laetitia Da; Allayous, Clara; Baroudjian, Barouyr; Jebali, Majdi; Herms, F.; Grzelak, Ludivine; Staropoli, Isabelle; Calmettes, Vincent; Hadjadj, Jérôme; Peyrony, Olivier; Cassius, C.; LeGoff, Jérôme; Kramkimel, N.; Aractingi, S.; Fontes, Magnus; Blanc, Catherine; Rieux‐Laucat, Frédéric; Schwartz, Olivier; Terrier, B.; Duffy, Darragh; Lebbe, Célèste

doi:10.1126/sciadv.abg4081

Cited by 31 publications

(22 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Patients who have recovered from SARS-CoV-2 presumably acquire cellular immunity to various viral antigens, while the vaccine creates immunity only against the spike protein, which may be the reason for the significantly reduced reinfection rate in patients who have recovered from SARS-CoV-2. However, we could not confirm or dismiss this presumption, as we did not test the immune response to other viral antigens [ 27 , 28 , 29 , 30 ]. Due to the importance of T-cell immunity, the development of a new vaccine that will primarily stimulate cellular immunity has begun.…”

Section: Discussionmentioning

confidence: 99%

Cellular Immunity—The Key to Long-Term Protection in Individuals Recovered from SARS-CoV-2 and after Vaccination

Primorac

Brlek²,

Matišić³

et al. 2022

Vaccines

View full text Add to dashboard Cite

Previous clinical and epidemiological studies have shown that over time antibody titers decrease, and they do not provide long-term mucosa protection against SARS-CoV-2 infection. Additionally, the increase in breakthrough infections that occur more frequently in the vaccinated than in the study participants with previous SARS-CoV-2 infection has recently become a priority public health concern. We measured the amount of interferon-gamma (Quan-T-Cell ELISA) and the level of antibodies (Anti-SARS-CoV-2 QuantiVac ELISA IgG) in the blood of the same patients simultaneously to compare cellular and humoral immunity. A total of 200 study participants (before Omicron variant appearance) were divided into four groups whose levels of cellular and humoral immunity we compared: study participants previously infected with SARS-CoV-2 (group 1); study participants vaccinated with EMA-approved vaccines (group 2); study participants previously infected with SARS-CoV-2, and vaccination history (group 3); and study participants without a history of SARS-CoV-2 infection or vaccination (group 4). Our results showed that study participants who received one of the EMA-approved vaccines and who recovered from COVID-19 (group 3) had significantly higher levels of cellular immunity and antibody titers in comparison with groups 1 and 2. Additionally, we have noticed that the study participants previously infected with SARS-CoV-2 and the study participants vaccinated with EMA-approved vaccines had a long-lasting cellular immunity. Furthermore, antibody levels showed a negative correlation with time since the last contact with a viral antigen, while cellular immunity within 20 months showed as long-term protection. Moreover, out of 200 study participants, only 1 study participant who recovered from COVID-19 (0.5%) was re-infected, while a total of 6 study participants (3%) were infected with SARS-CoV-2 after receiving the vaccine. This study suggests that cellular immunity—unlike humoral immunity, thanks to memory T cells—represents long-term protection in individuals recovered from SARS-CoV-2 and after vaccination.

show abstract

Section: Discussionmentioning

confidence: 99%

Cellular Immunity—The Key to Long-Term Protection in Individuals Recovered from SARS-CoV-2 and after Vaccination

Primorac

Brlek²,

Matišić³

et al. 2022

Vaccines

View full text Add to dashboard Cite

show abstract

“…Such concerns have prompted some physicians and patients to discontinue anti-PD-1 therapy during anti-COVID-19 vaccination. Although studies have shown that anti-COVID-19 vaccination in patients with cancer is safe 13 and because ICI treatment does not increase the severity of COVID-19 infection, 14 until now, little data existed regarding the implications of anti-COVID-19 vaccination on the safety and efficacy of PD-1 inhibitor treatment.…”

Section: Discussionmentioning

confidence: 99%

Impact of COVID-19 vaccination on the use of PD-1 inhibitor in treating patients with cancer: a real-world study

Mei

Yang

et al. 2022

J Immunother Cancer

View full text Add to dashboard Cite

Anti-COVID-19 vaccination may have functional implications for immune checkpoint inhibitor treatment in patients with cancer. This study was undertaken to determine whether the safety or efficacy of anti-PD-1 therapy is reduced in patients with cancer during COVID-19 vaccination. A large multicenter observational study was conducted in 83 Chinese hospitals between January 28, 2021 and September 30, 2021. A total of 3552 patients were screened and 2048 eligible patients with cancer receiving PD-1 inhibitor treatment were recruited. All enrolled patients had received camrelizumab treatment alone or in conjunction with other cancer therapies. Among these, 1518 (74.1%) patients received the BBIBP-CorV vaccine and were defined as the vaccinated subgroup. The remaining 530 (25.9%) patients did not receive anti-COVID-19 vaccination and were defined as the non-vaccinated subgroup. For all participants, Response Evaluation Criteria in Solid Tumor and Common Terminology Criteria for Adverse Events criteria were used to evaluate the efficacy and safety of camrelizumab treatment, respectively. Propensity score match analysis with the optimal pair matching was used to compare these criteria between the vaccinated and non-vaccinated subgroups. A total of 2048 eligible patients with cancer were included (median age 59 years, 27.6% female). Most patients (98.8%) had metastatic cancer of the lung, liver or intestinal tract. Aside from the PD-1 inhibitor treatment, 55.9% of patients received additional cancer therapies. 1518 (74.1%) patients received the BBIBP-CorV vaccine with only mild side effects reported. The remaining patients did not receive COVID-19 vaccination and had a statistically greater percentage of comorbidities. After matching for age, gender, cancer stage/types, comorbidity and performance status, 1060 patients (530 pairs) were selected for propensity score match analysis. This analysis showed no significant differences in overall response rate (25.3% vs 28.9%, p=0.213) and disease control rate (64.6% vs 67.0%, p=0.437) between vaccinated and non-vaccinated subgroups. Immune-related adverse events (irAEs) were reported in both subgroups after camrelizumab treatment. Among vaccinated patients who experienced irAEs, the median interval between the first dose of camrelizumab treatment and the first vaccine shot was ≤16 days. Compared with the non-vaccinated subgroup, irAEs in vaccinated patients were more frequently reported as mild (grade 1 or 2 irAEs; 33.8% vs 19.8%, p<0.001) and these patients were less likely to discontinue the PD-1 inhibitor treatment (4.2% vs 20.4%, p<0.001). Severe irAEs (grade 3 irAE or higher) related to camrelizumab treatment were reported, however no significant differences in the frequency of such events were observed between the vaccinated and non-vaccinated subgroups. The COVID-19 vaccine, BBIBP-CorV, did not increase severe anti-PD-1-related adverse events nor did it reduce the clinical efficacy of camrelizumab in patients with cancer. Thus, we conclude that patients with cancer need not suspend anti-PD-1 treatment during COVID-19 vaccination.

show abstract

“…Rather, the beneficial effects of an improved CD8 T-cell response may outweigh any minimal enhancement in immunopathology. Indeed, a recent study reported that immune checkpoint inhibitors can increase the T cell response in SARS-CoV-2 infected melanoma patients, without interfering with early interferon induction or aggravating inflammation [112].…”

Section: Plos Pathogensmentioning

confidence: 99%

Modeling recapitulates the heterogeneous outcomes of SARS-CoV-2 infection and quantifies the differences in the innate immune and CD8 T-cell responses between patients experiencing mild and severe symptoms

2022

View full text Add to dashboard Cite

SARS-CoV-2 infection results in highly heterogeneous outcomes, from cure without symptoms to acute respiratory distress and death. Empirical evidence points to the prominent roles of innate immune and CD8 T-cell responses in determining the outcomes. However, how these immune arms act in concert to elicit the outcomes remains unclear. Here, we developed a mathematical model of within-host SARS-CoV-2 infection that incorporates the essential features of the innate immune and CD8 T-cell responses. Remarkably, by varying the strengths and timings of the two immune arms, the model recapitulated the entire spectrum of outcomes realized. Furthermore, model predictions offered plausible explanations of several confounding clinical observations, including the occurrence of multiple peaks in viral load, viral recrudescence after symptom loss, and prolonged viral positivity. We applied the model to analyze published datasets of longitudinal viral load measurements from patients exhibiting diverse outcomes. The model provided excellent fits to the data. The best-fit parameter estimates indicated a nearly 80-fold stronger innate immune response and an over 200-fold more sensitive CD8 T-cell response in patients with mild compared to severe infection. These estimates provide quantitative insights into the likely origins of the dramatic inter-patient variability in the outcomes of SARS-CoV-2 infection. The insights have implications for interventions aimed at preventing severe disease and for understanding the differences between viral variants.

show abstract

Immune checkpoint inhibitors increase T cell immunity during SARS-CoV-2 infection

Cited by 31 publications

References 55 publications

Cellular Immunity—The Key to Long-Term Protection in Individuals Recovered from SARS-CoV-2 and after Vaccination

Cellular Immunity—The Key to Long-Term Protection in Individuals Recovered from SARS-CoV-2 and after Vaccination

Impact of COVID-19 vaccination on the use of PD-1 inhibitor in treating patients with cancer: a real-world study

Modeling recapitulates the heterogeneous outcomes of SARS-CoV-2 infection and quantifies the differences in the innate immune and CD8 T-cell responses between patients experiencing mild and severe symptoms

Contact Info

Product

Resources

About