Safety and immunogenicity of influenza vaccine among HIV-infected adults: Conventional vaccine vs. intradermal vaccine

Abstract

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 HIV-infected adults aged 18 - 60 years: an inactivated intramuscular vaccine (Agrippal), a reduced-content intradermal vaccine (IDflu9μg) and a standard-content intradermal vaccine (IDflu15μg). Serum hemagglutination-inhibiting (HI) antibodies and INF-γ 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 IDflu9μg, and 28 IDflu15μg volunteers were included in this analysis. One month after vaccination, the GMTs and differences in INF-γ 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, CD4+ 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.

HIV-dependent depletion of influenza-specific memory B cells impacts B cell responsiveness to seasonal influenza immunisation

“…Many national health authorities recommend immunisation of HIV+ individuals against influenza due to potential for increased susceptibility and/or disease severity 19 . Conventional or adjuvanted influenza vaccines are immunogenic in HIV+ adults 20 21 22 23 and children 24 25 26 27 , however the induction and maintenance of influenza-specific antibody titres is frequently lower than in comparable HIV− controls, particularly in the absence of ART or in infected subjects with low CD4 T cell counts 24 26 28 29 30 31 . Similarly, the establishment of influenza vaccine-elicited memory B cell responses, as measured by polyclonal stimulation and B cell ELISpot, are diminished compared to healthy controls 12 .…”

Fractional dose of intradermal compared to intramuscular and subcutaneous vaccination - A systematic review and meta-analysis

“…Among the included studies (n = 51) [ [39] , [89] ], 19 studies compared ID immunisation to SC immunisation of which all, except one [ 87 ], were historic studies (1949–1981) [ 42 , 44 , 45 , 52 , 53 , 57 , 58 , 61 , 64 , [66] , [67] , [68] , [69] , [70] , 72 , 73 , 77 , 89 ]. Studies comparing IM immunisation with ID (n = 32) immunisation were conducted more recently and were all published after 2003 [ [39] , [40] , [41] , [46] , [47] , [48] , [49] , [50] , [51] , [54] , [55] , [56] , 59 , 60 , 62 , 63 , 65 , 71 , [74] , [75] , [76] , [78] , [79] , [80] , [81] , [82] , [83] , [84] , [85] , [86] , 88 ], with the exception of Brown et al [ 43 ] published in 1977. Study populations of the identified studies on influenza vaccines consisted of healthy adults, elderly, children (0–18 years), chronically ill and immunocompromised patients, or combinations of these groups.…”

“…Study populations of the identified studies on influenza vaccines consisted of healthy adults, elderly, children (0–18 years), chronically ill and immunocompromised patients, or combinations of these groups. Many (n = 19) studies did not report whether participants were immunised in the last six months with influenza vaccine [ 42 , 43 , 48 , 51 , 57 , 59 , 62 , 64 , 66 , 68 , 69 , 71 , 75 , 81 , 82 , 84 , 86 , 88 , 89 ].…”

“…All included trials studied inactivated influenza vaccines (IIVs). Types of IIVs used were mostly sub-virion vaccines (including both split and purified surface antigen vaccines) [ [39] , [40] , [41] , [46] , [47] , [48] , [49] , [50] , [51] , 54 , 56 , 59 , 60 , 62 , 65 , 71 , [74] , [75] , [76] , [78] , [79] , [80] , 82 , 83 , [85] , [86] , [87] ], and in several studies whole virus vaccines [ 64 , 77 , 89 ]. A large amount of studies did not report the type of IIV (n = 18) [ 42 , 44 , 45 , 52 , 53 , 55 , 57 , 58 , 61 , [66] , [67] , [68] , [69] , [70] , 72 , 73 , 81 , 88 ].…”

Vaccinations for the HIV-Infected Adult: A Review of the Current Recommendations, Part I

“…However, a more recent, smaller study of HIV-infected children and young adults did not show improved antibody responses with high-dose vaccination [ 40 ]. Intradermal vaccines have been studied, and although they allow for the use of smaller antigenic doses, they do not appear to elicit greater immune responses and may be associated with more local and systemic side effects [ 41 , 42 ]. Finally, the use of adjuvanted vaccines (e.g., with AS03 ® or MF59 ® adjuvants) have generally produced greater immune responses post-vaccination [ 38 , 43 – 45 ].…”