*Purpose: The new adjuvanted subunit recombinant herpes zoster vaccine (RZV; Shingrix™) may have potential utility in transplant patients for the prevention of shingles, but there are limited data on its immunogenicity in this population. We conducted a prospective study to evaluate RZV immunogenicity in lung transplant recipients (LTR) who are known to be at high risk for herpes zoster reactivation compared to other organ transplant recipients.

*Methods: We enrolled adult LTR ≥ 50 years of age and administered two doses of RZV at 0,2-6 months. VZV anti-glycoprotein E (gE) antibody concentrations, gE antibody avidity, and gE-specific polyfunctional CD4 T-cells (CD4 T-cells expressing at least 2 out of 4 activation markers assessed) were measured at baseline, after the first vaccine dose and 4-weeks after the second vaccine dose.

*Results: Of 50 enrolled LTRs, 49 received at least one vaccine dose. The median time from transplant was 3.0 years (IQR 1.0-5.0) and 24.5% of patients received the vaccine within the first year post-transplant. The gE-antibody concentration increased significantly from baseline to post-dose 1 (median optical density (OD) 1.96, IQR 1.17-2.89 vs. 3.41, IQR 2.54-3.81, p<0.001) and increased further after the second dose (median OD 3.63, IQR 3.39-3.86, p<0.001; Figure 1A). Vaccination also increased the avidity of gE specific antibodies (Figure 1B). The number of gE-specific polyfunctional CD4+ T-cells significantly expanded after each vaccine dose (median [IQR] at baseline was 85 CD4+ cells/10⁶ [46-180] vs. post-dose 1: 128 [82-353]; vs. post-dose 2: 361 [146-848]; Figure 1C). LTRs who were vaccinated later after transplantation had higher polyfunctional gE-specific CD4 cell counts at baseline (p=0.010) and a trend towards higher cell counts after the second vaccine (p=0.051). The most common local adverse event was pain (83.0%) and redness (31.9%). General symptoms such as transient myalgia (36.2%), fatigue (31.9%) or headache (23.4%) were also common. Three patients had a rejection episode within three months after the last vaccine dose and two patients developed shingles shortly after the first vaccine dose.

*Conclusions: We provide unique data for RZV in LTRs that demonstrates the ability to generate both humoral and cellular immune responses. Local and systemic reactogenicity events were common but self-limited. RZV can be considered an option for the prevention of shingles in lung transplant recipients.

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