Persistence of immune response to an adjuvanted varicella-zoster virus subunit vaccine for up to year nine in older adults

Abstract

Background: In adults aged ≥60 years, two doses of the herpes zoster subunit vaccine (HZ/su; 50 µg varicella-zoster virus glycoprotein E [gE] and AS01B Adjuvant System) elicited humoral and cell-mediated immune responses persisting for at least six years. We assessed immunogenicity nine years post-initial vaccination.

Methods: This open extension study (NCT02735915) followed 70 participants who received two HZ/su doses in the initial trial (NCT00434577). Blood samples to assess the cellular (intracellular cytokine staining) and humoral (ELISA) immunity were taken at year nine post-initial vaccination.

Results: Participants' mean age at dose 1 was 72.3 years. The fold increases over pre-vaccination in the mean frequency of gE-specific CD4+ T-cells expressing ≥2 activation markers plateaued from year four post-dose 1 until year nine. Anti-gE antibody geometric mean concentrations plateaued and remained above pre-vaccination levels from year four onwards. Immunogenicity at year nine was similar across age strata (60-69, ≥70 years) and confirmed statistical prediction model results using data for up to year six. Further modeling using all data up to year nine predicted immune responses would remain above the pre-vaccination level up to year 15.

Conclusion: In adults aged ≥60 years, HZ/su-induced immunogenicity remained above pre-vaccination levels for at least nine years post-initial vaccination.

Summary: After vaccination with HZ/su, both cell mediated and humoral immunity remained above pre-vaccination levels up to year 9 regardless of age group. Immune responses are predicted to remain above baseline up to 15 years post initial vaccination.

Keywords: herpes zoster; herpes zoster (shingles) vaccine; immunity; persistence; prediction modeling; prevention; subunit gE vaccine; varicella-zoster virus.

Figures

Figure 1.

The median frequencies of CD4+ T cells expressing at least two activation markers (among CD40 ligand, interleukin-2, tumor necrosis factor-α, and interferon-γ) per 106 cells after in-vitro stimulation with gE were measured by intracellular cytokine staining followed by flow cytometry. X indicates medians, the horizontal bars indicate Q1 and Q3, dashed lines indicate pre-vaccination values (Q1, median, Q3); PRE = before vaccination; PII(Mxx): xx months after the first dose of vaccination. Panel A: Overall population; Panel B: age cohort 60 – 69 years; Panel C: age cohort ≥ 70 years.

Figure 2.

Anti-gE antibody concentrations were determined by enzyme-linked immunosorbent assay. X indicates medians, the horizontal bars indicate Q1 and Q3, dashed lines indicate pre-vaccination values (Q1, median, Q3); PRE = before vaccination; PII(Mxx): xx months after the first dose of vaccination. Panel A: Overall population; Panel B: age cohort 60 – 69 years; Panel C: age cohort ≥ 70 years.

Figure 3.

Predicted geometric means of frequencies of gE-specific CD4[2+] T cells based on three statistical prediction models (piece-wise linear, power-law, Fraser).

Figure 4.

Predictions of anti-gE antibody geometric mean concentrations based on three statistical prediction models (piece-wise linear, power-law, Fraser).

Figure 5.

Prediction models for frequency of gE-specific CD4[2+] T cells 72 months vs 108 months (Subjects who received two doses of HZ/su VZV vaccine). Panel A: Piece-wise linear; Panel B: Power-law, Panel C: Fraser.

Figure 6.

Prediction models for anti-gE antibodies 72 months vs 108 months (Subjects who received two doses of HZ/su VZV vaccine). Panel A: Piece-wise linear; Panel B: Power-law; Panel C: Fraser.