Table 2.
Selected studies of influenza vaccine immunogenicity in immunocompromised populations.
| Study | Vaccine Formulation | Route of Administration | Study Population | Immunogenicity Outcome | Other outcomes |
|---|---|---|---|---|---|
| Hematopoietic Stem Cell Transplant (HSCT) | |||||
| Karras et al., 201331 | 1 dose (n = 33) vs. 2 doses (n = 32) standard TIV 4 weeks apart | Intramuscular | > 60 days post HSCT | No significant differences in seroprotection at 8 weeks for influenza H3N2 (19% vs. 19%), H1N1 (32% vs. 32%) and B (32% vs. 23%).. | |
| No differences in seroconversion | |||||
| Natori et al., 201738 | MF59 adjuvanted (n = 35) vs. nonadjuvanted (n = 32) standard TIV | Intramuscular | > 12 weeks post HSCT | Seroprotection rates after vaccination were similar.Seroconversion to at least one of three influenza vaccine antigens was present in 62.9% vs 53.1% (P = 0.42) | |
| Halasa et al., 201637 | High-dose 60 μg (n = 29) vs. Standard-dose 15 μg (n = 15) TIV | Intramuscular | > 6 months post HSCT | GMTs were higher in the HD group for H1N1 and H3N2.HD group had a higher Seroprotection rate for H3N2; 81% vs. 36% (P = 0.004). | Study not powered for immunogenicity.Greater local reactions in HD vaccine. |
| Ambati et al., 201539 | Virosomal adjuvanted (n = 21) vs. nonadjuvanted standard (n = 30) TIV | Intramuscular | HSCT before and after 6 months post-transplant | Seroprotection rates were poor in both cohorts (23% vs 13.3%). | The delta change of interferon-gamma production in response to influenza A/H1N1and influenza B antigens was significantly greater in individuals who received the virosomal vaccine. |
| Solid Organ Transplant (SOT) | |||||
| Cordero et al., 201764 | 1 dose (n = 211) vs. 2 doses (n = 213) standard TIV given 5 weeks apart | Intramuscular | > 1 month post SOT | Higher short-term seroconversion rate.Seroprotection at 10 weeks was higher in the booster group: 54% vs 43.2% for A(H1N1)pdm; 56.9% vs 45.5% for A(H3N2); and 83.4% vs 71.8% for influenza B (P < .05). | |
| Manuel et al., 200744 | 2 doses (n = 60) TIV given 4 weeks apart | Intramuscular + Intradermal 5 μg | > 3 months post lung transplant | Intradermal booster dose did not significantly improve overall immunogenicity above that achieved with the single intramuscular dose. | |
| Manuel et al., 201170 | TIV Intradermal (n = 41) vs Intramuscular (n = 44) | Intradermal (6 μg) vs. Intramuscular (15 μg) | > 3 months post-lung transplant | Overall seroconversion rate was low, but it was similar between groups. | |
| Seroprotection was 39% for H1N1, 83% for H3N2 and 29% for B strain in the intradermal group vs 28% for H1N1, 98% for H3N2 and 58% for B strain in the intramuscular group (p = 0.36 for H1N1, p = 0.02 for H3N2, p < 0.01 for B). | |||||
| aluch et al., 201346 | TIV ID (n = 107) vs IM (n = 105) | Intradermal (18 μg) vs. Intramuscular (15 μg) | > 3 months post | Similar immunogenicityCertain organ subgroups (liver and kidney patients) had higher response rates for influenza B in the ID vaccine group (p = 0.011). | Response was more likely in those ≥6 months post-transplant (53.2% vs. 19.2%; p = 0.001). |
| SOT | |||||
| Kumar et al., 201659 | MF59 adjuvanted (n = 31) vs. nonadjuvanted (n = 29) standard TIV | Intramuscular | > 3 months post | Geometric mean titers and seroprotection rates were similar between groups. | In a subgroup analysis of the 18–64 year age group, the adjuvanted vaccine showed significantly greater seroconversion rates compared to unadjuvanted vaccines. |
| Kidney transplant | |||||
| Natori et al., 201769 | High Dose 60μg (n = 84) vs Standard Dose 15μg (n = 77) TIV | Intramuscular | > 3 months post | Seroconversion to A/ H1N1, A/H3N2 and B strains were higher in HD vs. SD vaccine (p = 0.006, 0.002, 0.028 respectively). | |
| SOT | |||||
| Magnani et al., 200570 | MF59 adjuvanted (n = 21) vs. nonadjuvanted (n = 21) standard TIV | Intramuscular | > 6 months post Heart transplant | No significant difference between groups.Both were associated to a significant increase of antibodies belonging to the IgG and IgM classes to influenza B and of an IgM immune response to influenza A (p<0.05). | 4 episodes of acute myocardial rejection > 3A were detected during the 6 months of follow-up |
| GiaQuinta et al., 201568 | High Dose 60 μg (n = 23) vs Standard Dose 15 μg (n = 15) TIV | Intramuscular | Pediatric > 6 months post SOT | HD group demonstrated a higher percentage of four-fold titer rise to H3N2 (not powered to compare the immunogenicity). | HD group reported more tenderness and local reactions, fatigue, and body ache |
| Hojsak et al., 201166 | 1 dose (n = 18) vs. 2 doses (n = 32) standard TIV given 4–6 weeks apart | Intramuscular | Pediatric > 6 months post Liver Transplant | antibody titers were higher after second vaccination, but not statistically significant (P = 0.198). | |
| Hematologic Malignancy and Solid Tumour | |||||
| Ljungman et al., 200580 | 1 dose (n = 36) vs. 2 doses (n = 34) standard TIV given 4 weeks apart | Subcutaneous | Haematological malignancies on chemotherapy within 6 months | Seroprotection rates were not improved by two doses compared with one (influenza A virus serotypes H1/N1 18% vs. 22% and H3/N2 26% vs. 14%; influenza B 25% vs. 22%). | |
| Sanada et al., 201681 | 2 doses (n = 109) standard TIV given 3–5 weeks apart | Subcutaneous | Solid tumours and haematological malignancy on chemotherapy within 6 months | booster dose did not improve immunogenicity (seroprotction increased by only 10% (H1N1), 8% (H3N2), and 3% (B) after the 2nd vaccine). | |
| Jamshed et al., 201682 | High Dose 60 μg (n = 54) vs Standard Dose 15 μg (n = 51) TIV | Intramuscular | Solid tumours and haematological malignancy on chemotherapy | Significantly improved seroconversion rates with HD for all three strains (26% for H1N1, 22% for H3N2, and 36% for B).Seroprotection rates were equivalent and high in both groups for all three strains | |
| Hakim et al., 201683 | 2 doses of HD (60 μg) vs 2 doses SD (15 μg) TIV (1:1) given 21 days apart | Intramuscular | 27 with leukemia, 17 with solid tumour, and 41 with HIV | HD TIV was significantly more immunogenic against B antigen in leukemia patients (p = 0.04), and H1 antigen in Solid Tumor patients (p = 0.04). | HD TIV reported more frequent reactogenicity events but not statistically significant |
| McManus et al., 201484 | (HD 60 μg) (n = 34) vs (SD 15 μg) (n = 16) TIV | Intramuscular | Children with acute lymphoblastic leukemia | No significant differences (this study was not powered for immunogenicity) | Nine in the HD group and two in the SD group required two doses of the vaccine. |
| Inflammatory Disease and Biologic Therapy | |||||
| Matsumoto et al., 201592 | 1 dose (n = 46) vs. 2 doses (n = 43) standard TIV given 3 weeks apart | Subcutaneous | Adult inflammatory bowel disease patients treated with anti-tumor necrosis factor-α agents and/or immunomodulators | No significant difference 3 weeks post-vaccination (geometric mean titers: H1N1, p = 0.09; H3N2: p = 0.99; B: p = 0.94). | |
TIV trivalent inactivated vaccine, ID Intradermal, IM Intramuscular, HIV human immunodeficiency virus, HD high-dose, SD standard-dose, HSCT hematopoietic stem cell transplant, SOT solid organ transplant.