New COVID-19 vaccine may protect patients with B-cell deficiencies
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CoVac-1, a COVID-19 vaccine, induced T-cell responses in patients with B-cell deficiencies, including those with lymphoma and leukemia, according to study results presented during American Association for Cancer Research Annual Meeting.
“CoVac-1-induced T cell responses were documented in all but one of these highly immunocompromised patients,” Juliane Walz, MD, professor of peptide-based immunotherapy at University Hospital Tübingen in Germany, and Claudia Tandler, MSc, graduate student in the department of peptide-based immunotherapy at University of Tübingen, told Healio in a joint statement. “It is directed to different viral components (not limited to the spike protein) and thus not affected by any of the reported variants of concern, including omicron. The T-cell responses it induced exceed spike-specific T-cell responses induced by mRNA-based vaccines in immunocompromised patients.”
Background and methodology
Walz, Tandler and colleagues understood that individuals with impaired ability to mount a humoral immune response are at high risk for severe COVID-19 and that T-cell immunity is crucial for the control of viral infections.
“Many patients with cancer, especially those receiving B-cell-depleting therapy, do not mount sufficient humoral, ie antibody-mediated, immune responses after vaccination with available COVID-19 vaccines,” Walz and Tandler told Healio. “These patients are thus at high risk for severe courses of COVID-19. Therefore, we decided early in the pandemic to use our longstanding expertise in the development of therapeutic T-cell-inducing cancer vaccines to develop a COVID-19 “T-cell activator” especially for this high-risk patient cohort.”
The first phase of the phase 1/phase 2 trial included 14 patients with a B-cell deficiency (median age, 65 years; range, 40-80; 71% men; n = 12 with leukemia or lymphoma), including nine who previously received a vaccine that failed to elicit a humoral immune response. The phase 2 portion included an additional 40 patients (median age, 61 years; range, 37-90; 73% men; n = 38 with leukemia, lymphoma or other cancer), 32 of whom had received an approved vaccine but did not develop an antibody response.
Walz, Tandler and colleagues administered a single dose of CoVac-1 and monitored patients for up to 6 months for safety and immunogenicity.
Primary objectives included safety and tolerability (phase 1), and efficacy, defined as induction of SARS-CoV-2-specific T cells (phase 2).
Key findings
Results of the safety analysis showed expected local adverse events, such granuloma, but no inflammatory systemic adverse events.
Results of the phase 1/phase 2 immunogenicity analysis showed T-cell immune responses in 62% of patients 14 days after vaccination and 86% of patients after 28 days.
Walz, Tandler and colleagues reported the potency of CoVac-1-induced T-cell responses exceeded spike-specific T-cell responses observed in B-cell-deficient patients after vaccination with mRNA vaccines. Additionally, they noted T-cell responses from CoVac-1 exceeded those mounted by individuals who are not immunocompromised following COVID-19 infection.
Implications
Preparations are underway for a phase 3 trial, in which Walz, Tander and colleagues will evaluate the vaccine among a larger population of immunocompromised patients.
“In addition to individuals with acquired or congenital immune defects, healthy, elderly people are still vulnerable to severe courses of COVID-19, as they benefit only for a short time from currently available vaccines. Therefore, in midterm, we plan to evaluate CoVac-1 also in this cohort to further help to protect these individuals from severe courses of COVID-19,” Walz and Tandler told Healio.
During a press conference, moderator Ana María López, MD, MPH, MACP, FRCP, professor and vice chair of medical oncology at Sidney Kimmel Medical College and chief of cancer services at Sidney Kimmel Cancer Center — Jefferson Health New Jersey, commented on the significance of the study.
“We know there are patients with hematologic malignancies — for example, elders — who may not be able to mount a response to the existing vaccines,” López said. “Therefore, having an option for these patients is just critical.”
References:
Novel COVID-19 vaccine may provide protection for cancer patients with B-cell deficiencies (press release). Available at: www.aacr.org/about-the-aacr/newsroom/news-releases/novel-covid-19-vaccine-may-provide-protection-for-cancer-patients-with-b-cell-deficiencies/. Published April 12, 2022. Accessed April 12, 2022.
Tandler C, et al. Abstract CT258. Presented at American Association for Cancer Research Annual Meeting; April 8-13, 2022; New Orleans.
Perspective
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The success of mRNA vaccines against SARS-CoV-2 has been remarkable, considering that prior to the pandemic, there had been no large-scale testing and distribution of vaccines of that nature. More than 11 billion doses have been injected into about half of the world’s population with great efficacy and limited numbers of adverse events. Giving additional doses or boosters has extended the efficacy of mRNA vaccines to new forms of the SARS-CoV-2 virus termed variants of concern. Yet, there are groups of individuals who have not effectively immunologically responded to the vaccines. These include patients whose B cells are incapacitated as a result of targeted therapies necessary to control underlying malignancies such as chronic lymphocytic leukemia, lymphoma or other B-cell neoplasms.
Although not as intensively studied as the antibody responses, the cellular arm of the immune system, especially T cells, has been the object of investigations during the entire pandemic vaccination period. Many different platforms evoke T-cell responses, as it has been shown that the co-immunodominant spike and nucleocapsid antigens are effectively processed in human antigen-presenting cells.
The abstract by Tandler and colleagues attempts to distinguish a vaccine of their invention, coined CoVac-1, as a strong stimulator of T-cell responses. In fact, because of the “beads-on-a-string” design of the vaccine as a series of T-cell epitopes from a variety of viral proteins, it has diminished capacity to elicit humoral and neutralizing antibody responses.
The report published earlier this year detailing T-cell responses in healthy adults showed that after one vaccination, good, measured levels of CD4 T cells occurred that had multiple cytokine functions. Two months after vaccination, median levels dropped by 50%, but a correlate of protection is unknown, so the reduced levels — if they remain stable — may be sufficient to prevent hospitalization and death.
The report from the clinical trial described in the abstract is that patients with B-cell deficiency who had mainly been unable to mount an antibody response after vaccination with approved vaccines had good T-cell responses after booster vaccination with CoVac-1. These are promising data, but there are many unanswered questions. How durable is the T-cell upregulation? Are these T-cell responses protective against lower respiratory tract infection, and will they have any impact against acquiring the infection in the first place? Are any of the patients on active therapy such as rituximab or other B-cell- or T-cell-depleting or immunosuppressive agents? Considering reports of durable T-cell responses elicited by many of the approved and investigational vaccines, how is this vaccine superior for protection of B-cell-deficient patients?
Answers to these questions will lay the groundwork for advancement of this vaccine concept into authorization in Europe, the United States and, ultimately, worldwide.
Reference:
Heitmann JS, et al. Nature. 2022;doi:10.1038/s41586-021-04232-5.
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Tandler C, et al. Abstract CT258. Presented at American Association for Cancer Research Annual Meeting; April 8-13, 2022; New Orleans.
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