Herpes Zoster Vaccine Elicits Robust Immune Response in HSCT Patients

Keith Sullivan, MD, associate professor of oncology and urology at Johns Hopkins Medicine

Keith Sullivan, MD

Two doses of adjuvanted recombinant zoster vaccine (RZV, Shingrix) following autologous hematopoietic stem cell transplant (aHSCT) led to rapid and durable cell-mediated immune (CMI) responses, results from a subgroup analysis of a large randomized, placebo-controlled trial showed.¹

An increase in the frequency of CD4(2+) T cells was evident within 1 month of the first dose of vaccine, reached a peak within 1 month after the second dose, and persisted during follow-up for 24 months. Almost half (46.3%) of the patients had a CMI response 1 month after having received the first dose of the vaccine, with responses increasing to 92.9% within a month after the second dose was received. At 24 months, 70.8% of patients still met response criteria, as was reported at the Transplantation & Cellular Therapy (TCT) Meetings.

“We observed a robust cell mediated immunogenicity in recombinant zoster vaccine recipients at all time points after first vaccination, compared with little response to placebo,” said Keith Sullivan, MD, of Duke University Medical Center. “The results also showed a robust polyfunctional response of T cell repertoire following first and second vaccinations.”

“These are very impressive results,” he added. “We are not accustomed to seeing this type of immune response in such an immunosuppressed patient population.”

Immunocompromised individuals—especially patients undergoing aHSCT—have an increased risk of herpes zoster. Investigators hypothesized that administration of 2 doses of the RZV shortly after aHSCT would protect against herpes zoster and induce robust immune responses.

At the 2018 TCT meetings, investigators reported primary results from a randomized, placebo-controlled trial involving 1800 patients who underwent aHSCT. The data showed that the vaccine achieved a 68.2% efficacy against herpes zoster and 89.3% efficacy against postherpetic neuralgia.²

Sullivan reported findings from an analysis of the humoral and cellular immune response to the vaccine. The analysis included 141 randomized patients, 114 of whom were treated according to protocol. Baseline characteristics were well balanced between the groups. The patients had a median age of about 55, and men accounted for about two-thirds of the subgroup.

CMI response was measured in peripheral blood mononuclear cells and expressed as frequencies of gE-specific CD4+ T cells expressing ≥2 activation markers per 10⁶ T cells (CD4[2+]/10⁶). Investigators performed post hoc analysis of polyfunctionality, summarizing the median frequencies of CD4+ T cells expressing 1, 2, 3, or 4 markers. All patients had a minimum follow-up of 1 year.

In the patients randomized to receive the RZV, the median frequency of CD4(2+) T cells increased from 48.9 prevaccination to 570.3 at 1 month after the first vaccine dose and peaked at 6644.9 at 1 month after the second dose. The median frequency remained at 1706.4 1 year after the second dose in 32 evaluable patients and was 2294.4 at 2 years in 30 evaluable patients. In contrast, patients randomized to receive placebo had a baseline CD4(2+) frequency of 65.0 and reached a peak of 97.0 at the 24-month follow-up (18 patients).

With respect to CMI response, 46.3% of patients who received the vaccine met response criteria within 1 month of the first dose. The response rate peaked at 92.9% at 1 month after the second vaccine dose, and 70.8% of 24 evaluable patients met response criteria at 24 months. No patient in the placebo group met response criteria until 12 months of follow-up (7.7%), and the response rate stood at 12.5% at 24 months among 16 evaluable patients.

In the prevaccinated group, 65.7% of study participants had expression of a single activation marker for CD4+ T cells, 15.2% had 2 markers, 8.4% had 3 markers, and 10.7% had all 4 markers (interferon-gamma, tumor necrosis factor-alpha, interleukin-2, and CD40L). By 1-month post-dose 1, 27.0% of patients expressed 1 marker, 17.9% expressed 2, 25.8% expressed 3, and 29.3% expressed all 4.

The distribution of activation markers continued to shift throughout 24 months of follow-up, at which time 50.3% of patients expressed all 4 activation markers, 29.3% expressed 3, 9.5% expressed 2, and 10.9% expressed 1.

“This indicates immune memory and represents a novel finding in such an immunocompromised population, where CD4+ T-cell functionality data are scarce,” Sullivan and colleagues concluded in a poster presentation. “The observed frequencies of CD4+ T cells expressing 2, 3, or 4 activation markers appear similar to those elicited by RZV in the general adult population ≥50 years of age.”

References

1. Sullivan K, Stadtmauer E, Salaun B, et al. Cell-mediated immunogenicity of the adjuvanted recombinant zoster vaccine (RZV) in adult autologous hematopoietic stem cell transplant recipients: a phase 3, randomized, placebo-controlled zoe-HSCT clinical trial. Presented at: Transplantation and Cellular Therapy Meetings. February 20-24, 2019; Houston, TX. Poster LBA32.
2. de la Serna J, Campora L, Chandrasekar P, et al. Efficacy and safety of an adjuvanted herpes zoster subunit vaccine in autologous hematopoietic stem cell transplant recipients 18 years of age or older: first results of the phase 3 randomized, placebo-controlled ZOE-HSCT clinical trial. Presented at: 2018 TCT Meetings. February 21-25, 2018; Salt Lake City, UT. Abstract LBA2.

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