Human Vaccines & Immunotherapeutics
ISSN: 2164-5515 (Print) 2164-554X (Online) Journal homepage: http://www.tandfonline.com/loi/khvi20
Safety and immunogenicity of influenza vaccine among HIV-infected adults: Conventional vaccine vs. intradermal vaccine Yu Bin Seo, Jacob Lee, Joon Young Song, Hee Jung Choi, Hee Jin Cheong & Woo Joo Kim To cite this article: Yu Bin Seo, Jacob Lee, Joon Young Song, Hee Jung Choi, Hee Jin Cheong & Woo Joo Kim (2016) Safety and immunogenicity of influenza vaccine among HIV-infected adults: Conventional vaccine vs. intradermal vaccine, Human Vaccines & Immunotherapeutics, 12:2, 478-484, DOI: 10.1080/21645515.2015.1076599 To link to this article: http://dx.doi.org/10.1080/21645515.2015.1076599
Accepted author version posted online: 02 Oct 2015.
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Date: 15 March 2016, At: 02:00
RESEARCH PAPER Human Vaccines & Immunotherapeutics 12:2, 478--484; February 2016; © 2016 Taylor and Francis Group, LLC
Safety and immunogenicity of influenza vaccine among HIV-infected adults: Conventional vaccine vs. intradermal vaccine Yu Bin Seo1, Jacob Lee1, Joon Young Song2, Hee Jung Choi3, Hee Jin Cheong2,*, and Woo Joo Kim2 1 Division of Infectious Diseases; Department of Internal Medicine; Hallym University College of Medicine; Chuncheon, Republic of Korea; 2Division of Infectious Diseases; Department of Internal Medicine; Korea University College of Medicine; Seoul, Republic of Korea; 3Division of Infectious Diseases; Department of Internal Medicine; Ewha Woman University College of Medicine; Seoul, Republic of Korea
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Keywords: HIV, influenza vaccine, intradermal vaccine, immunogenicity, safety
Several studies have reported poor immune responses to conventional influenza vaccines in HIV-infected individuals. This study sought to elicit more potent immunogenicity in HIV-infected adults using an intradermal vaccine compared with a conventional intramuscular vaccine. This multicenter, randomized, controlled, open-label study was conducted at 3 university hospitals during the 2011/2012 pre-influenza season. Three vaccines were used in HIVinfected adults aged 18 – 60 years: an inactivated intramuscular vaccine (Agrippal), a reduced-content intradermal vaccine (IDflu9mg) and a standard-content intradermal vaccine (IDflu15mg). Serum hemagglutination-inhibiting (HI) antibodies and INF-g ELISpot assay were measured at the time of vaccination and 1 month after vaccination. Adverse events were recorded for 7 d. A total of 28 Agrippal, 30 IDflu9mg, and 28 IDflu15mg volunteers were included in this analysis. One month after vaccination, the GMTs and differences in INF-g ELISpot assay results were similar among the 3 groups. Seroprotection rates, seroconversion rates and mean fold increases (MFI) among the 3 groups were also similar, at approximately 80%, 50–60% and 2.5 – 10.0, respectively. All three vaccines satisfied the CHMP criteria for the A/H1N1 and A/H3N2 strains, but not those for the B strain. In univariate analysis, no demographic or clinical factors, including age, CD4C T-cell counts, HIV viral load, ART status and vaccine type, were related to failure to achieve seroprotection. The three vaccines were all well-tolerated and all reported reactions were mild to moderate. However, there was a tendency toward a higher incidence of local and systemic reactions in the intradermal vaccine groups. The intradermal vaccine did not result in higher immunogenicity compared to the conventional intramuscular vaccine, even with increased antigen dose.
Introduction Human immunodeficiency virus (HIV)-infected individuals have both lower humoral and cell-mediated immunity. As a consequence, they are considered to be at risk for influenza infection and its complications. Although well-designed epidemiologic studies have been limited, several small studies have demonstrated that HIV-infected individuals are more likely to have severe or prolonged influenza infections.1,2 For this reason, annual influenza immunization is recommended for patients with HIV, and an inactivated intramuscular vaccine is routinely administered. Several studies have shown poor immune responses to conventional influenza vaccines in HIV-infected individuals compared with healthy uninfected individuals.3-5 CD4C T-cell count and HIV viral load have generally been considered to be the main factors that contribute to poor immunogenicity.6,7 Although widespread use of antiretroviral therapy (ART) has restored the
immune deficit in these patients, influenza vaccination has still resulted in suboptimal immunogenicity in HIV-infected individuals.8,9 To overcome this hypo-responsiveness, several strategies, including use of adjuvants, boosters or high doses of vaccine, have been proposed. However, the results remain controversial and additional data are needed. An intradermal influenza vaccine has recently been introduced. With brand name IDfluÒ (Sanofi Pasteur, Lyon, France), this is delivered using the Micro-Injection System that consists of a pre-filled syringe with a micro-needle (1.5 mm) and a needle shielding system. It is available as a 9 mg HA formulation for adults 18–59 y of age and as a 15 mg HA formulation for adults 60 y of age. Intradermal vaccines elicit comparable or superior immune reactions compared with conventional vaccines in healthy adults.10,11 To this end, we conducted this study expecting that an intradermal vaccine would elicit more potent immunogenicity in HIV-infected adults, compared with a conventional intramuscular vaccine.
*Correspondence to: Hee Jin Cheong; Email: [email protected] Submitted: 05/13/2015; Revised: 07/05/2015; Accepted: 07/22/2015 http://dx.doi.org/10.1080/21645515.2015.1076599
478
Human Vaccines & Immunotherapeutics
Volume 12 Issue 2
Downloaded by [Florida Atlantic University] at 02:00 15 March 2016
Results Study participant characteristics A total of 90 participants were enrolled (Agrippal, nD30; IDflu9mg, n D 30; and IDflu15 mg, nD30). Because four participants did not complete a second visit, data were available for 86 participants (Agrippal, n D 28; IDflu9mg, n D 30; and IDflu15 mg, n D 28). They declined the second visit for no definite reasons. Table 1 shows the baseline characteristics of these 86 participants. Males were more common than females, and the median age was 40. The majority were on ART with a mean CD4C count of 483 and HIV RNA levels
ISSN: 2164-5515 (Print) 2164-554X (Online) Journal homepage: http://www.tandfonline.com/loi/khvi20
Safety and immunogenicity of influenza vaccine among HIV-infected adults: Conventional vaccine vs. intradermal vaccine Yu Bin Seo, Jacob Lee, Joon Young Song, Hee Jung Choi, Hee Jin Cheong & Woo Joo Kim To cite this article: Yu Bin Seo, Jacob Lee, Joon Young Song, Hee Jung Choi, Hee Jin Cheong & Woo Joo Kim (2016) Safety and immunogenicity of influenza vaccine among HIV-infected adults: Conventional vaccine vs. intradermal vaccine, Human Vaccines & Immunotherapeutics, 12:2, 478-484, DOI: 10.1080/21645515.2015.1076599 To link to this article: http://dx.doi.org/10.1080/21645515.2015.1076599
Accepted author version posted online: 02 Oct 2015.
Submit your article to this journal
Article views: 34
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=khvi20 Download by: [Florida Atlantic University]
Date: 15 March 2016, At: 02:00
RESEARCH PAPER Human Vaccines & Immunotherapeutics 12:2, 478--484; February 2016; © 2016 Taylor and Francis Group, LLC
Safety and immunogenicity of influenza vaccine among HIV-infected adults: Conventional vaccine vs. intradermal vaccine Yu Bin Seo1, Jacob Lee1, Joon Young Song2, Hee Jung Choi3, Hee Jin Cheong2,*, and Woo Joo Kim2 1 Division of Infectious Diseases; Department of Internal Medicine; Hallym University College of Medicine; Chuncheon, Republic of Korea; 2Division of Infectious Diseases; Department of Internal Medicine; Korea University College of Medicine; Seoul, Republic of Korea; 3Division of Infectious Diseases; Department of Internal Medicine; Ewha Woman University College of Medicine; Seoul, Republic of Korea
Downloaded by [Florida Atlantic University] at 02:00 15 March 2016
Keywords: HIV, influenza vaccine, intradermal vaccine, immunogenicity, safety
Several studies have reported poor immune responses to conventional influenza vaccines in HIV-infected individuals. This study sought to elicit more potent immunogenicity in HIV-infected adults using an intradermal vaccine compared with a conventional intramuscular vaccine. This multicenter, randomized, controlled, open-label study was conducted at 3 university hospitals during the 2011/2012 pre-influenza season. Three vaccines were used in HIVinfected adults aged 18 – 60 years: an inactivated intramuscular vaccine (Agrippal), a reduced-content intradermal vaccine (IDflu9mg) and a standard-content intradermal vaccine (IDflu15mg). Serum hemagglutination-inhibiting (HI) antibodies and INF-g ELISpot assay were measured at the time of vaccination and 1 month after vaccination. Adverse events were recorded for 7 d. A total of 28 Agrippal, 30 IDflu9mg, and 28 IDflu15mg volunteers were included in this analysis. One month after vaccination, the GMTs and differences in INF-g ELISpot assay results were similar among the 3 groups. Seroprotection rates, seroconversion rates and mean fold increases (MFI) among the 3 groups were also similar, at approximately 80%, 50–60% and 2.5 – 10.0, respectively. All three vaccines satisfied the CHMP criteria for the A/H1N1 and A/H3N2 strains, but not those for the B strain. In univariate analysis, no demographic or clinical factors, including age, CD4C T-cell counts, HIV viral load, ART status and vaccine type, were related to failure to achieve seroprotection. The three vaccines were all well-tolerated and all reported reactions were mild to moderate. However, there was a tendency toward a higher incidence of local and systemic reactions in the intradermal vaccine groups. The intradermal vaccine did not result in higher immunogenicity compared to the conventional intramuscular vaccine, even with increased antigen dose.
Introduction Human immunodeficiency virus (HIV)-infected individuals have both lower humoral and cell-mediated immunity. As a consequence, they are considered to be at risk for influenza infection and its complications. Although well-designed epidemiologic studies have been limited, several small studies have demonstrated that HIV-infected individuals are more likely to have severe or prolonged influenza infections.1,2 For this reason, annual influenza immunization is recommended for patients with HIV, and an inactivated intramuscular vaccine is routinely administered. Several studies have shown poor immune responses to conventional influenza vaccines in HIV-infected individuals compared with healthy uninfected individuals.3-5 CD4C T-cell count and HIV viral load have generally been considered to be the main factors that contribute to poor immunogenicity.6,7 Although widespread use of antiretroviral therapy (ART) has restored the
immune deficit in these patients, influenza vaccination has still resulted in suboptimal immunogenicity in HIV-infected individuals.8,9 To overcome this hypo-responsiveness, several strategies, including use of adjuvants, boosters or high doses of vaccine, have been proposed. However, the results remain controversial and additional data are needed. An intradermal influenza vaccine has recently been introduced. With brand name IDfluÒ (Sanofi Pasteur, Lyon, France), this is delivered using the Micro-Injection System that consists of a pre-filled syringe with a micro-needle (1.5 mm) and a needle shielding system. It is available as a 9 mg HA formulation for adults 18–59 y of age and as a 15 mg HA formulation for adults 60 y of age. Intradermal vaccines elicit comparable or superior immune reactions compared with conventional vaccines in healthy adults.10,11 To this end, we conducted this study expecting that an intradermal vaccine would elicit more potent immunogenicity in HIV-infected adults, compared with a conventional intramuscular vaccine.
*Correspondence to: Hee Jin Cheong; Email: [email protected] Submitted: 05/13/2015; Revised: 07/05/2015; Accepted: 07/22/2015 http://dx.doi.org/10.1080/21645515.2015.1076599
478
Human Vaccines & Immunotherapeutics
Volume 12 Issue 2
Downloaded by [Florida Atlantic University] at 02:00 15 March 2016
Results Study participant characteristics A total of 90 participants were enrolled (Agrippal, nD30; IDflu9mg, n D 30; and IDflu15 mg, nD30). Because four participants did not complete a second visit, data were available for 86 participants (Agrippal, n D 28; IDflu9mg, n D 30; and IDflu15 mg, n D 28). They declined the second visit for no definite reasons. Table 1 shows the baseline characteristics of these 86 participants. Males were more common than females, and the median age was 40. The majority were on ART with a mean CD4C count of 483 and HIV RNA levels
