Antibody response after influenza vaccination in HIV-infected individuals: a consecutive 3-year study☆
Introduction
The manifestations of HIV-infection consist mainly of opportunistic infections related to an impaired cell-mediated immune response. Consistent with the major role of the cellular immune system is the occurrence of viral infections with e.g. herpes simplex virus, varicella zoster virus, cytomegalovirus and Epstein Bar virus in AIDS patients [1]. Antibodies play an important role in the host defence against influenza [2]. It is conceivable that HIV-infected individuals are more susceptible to influenza than healthy individuals since humoral immunity is also affected in these patients [3], [4], [5]. Infections caused by a number of other viruses, including e.g. influenza virus, do not seem to be a problem, but there is little information regarding the morbidity and mortality of influenza in HIV-infected individuals [6], [7], [8]. Health authorities of many countries recommend annual vaccination against influenza for HIV-infected individuals [9], [10], [11].
Induction of antibodies after vaccination or infection with influenza is a T-lymphocyte-dependent process. We have demonstrated that the formation of haemagglutination-inhibitory (HAI) antibodies after influenza vaccination is severely impaired in HIV-infected individuals with CD4+ T-lymphocyte counts <100×106/l [12]. Influenza virus antigens induce, at least partially, a recall response in which CD4+ T-memory lymphocytes play a dominant role [13], [14]. Annual vaccination with the same or a similar antigen might induce an immunological memory which could enhance the immune response to subsequent vaccination or infection. In HIV-infected individuals, the loss of memory T lymphocytes and the loss of the capacity to respond to recall antigens by the remaining memory cells has already been observed early in HIV-infection [15]. In later stages of HIV infection the responses of both naive and memory CD4+ T-lymphocytes are affected [16]. Consequently, the generation of T-cell memory and the humoral immune response upon subsequent vaccination may be impaired.
We performed a prospective study of HIV-infected individuals to investigate whether annual vaccination with influenza vaccines leads to higher postvaccination antibody titres and a greater proportion of individuals with protective antibody titres compared with individuals vaccinated for the first time.
Section snippets
Vaccinations
HIV-infected individuals without an active opportunistic infection who visited the Infectious Diseases outpatient clinic of the Leiden University Medical Center were eligible for this study and were invited by letter to participate. Healthy adults without risk factors for HIV-infection served as controls. Between November 1991 and February 1992 we immunized these individuals with tetravalent influenza split-vaccine (one single lot of Vaxigrip®, formulation 1991–1992, Institut Mérieux, Lyon,
Adverse reactions to vaccinations
The vaccinations were well-tolerated. Some individuals reported mild soreness at the site of the injection. Vaccination in consecutive years did not increase the number or severity of the side-effects.
Course of CD4+ T lymphocytes
After each vaccination the number of CD4+ T lymphocytes for all patients at 30 days did not differ (p>0.1) from the number before vaccination (analyzed separately for each year). Due to the natural course of the number of CD4+ T-lymphocytes during HIV-infection, after an interval of 1 year there
Discussion
Two conclusions can be drawn from this study. First, HIV-infected individuals have an impaired antibody response to influenza vaccination compared with healthy controls. The degree of impairment correlates with the decrease of CD4+ counts; in HIV-infected individuals with CD4+ T-lymphocyte counts ≤100×106/l the antibody response is almost absent. Secondly, in HIV-infected individuals, vaccination in the previous year did not led to an increased antibody response after vaccination the next year.
Future perspectives
Even after annual vaccination the proportion of HIV-infected individuals with low CD4+ T-lymphocyte counts with protective antibody titres remains low. The process of immune response involves many components of the immune system, e.g. antigen-presenting cells, naive and memory T-lymphocytes as well as B-lymphocytes. The functionality of these essential elements of the immune system is known to deteriorate in HIV-infected individuals [47]. Recent studies indicate that during treatment with
Acknowledgements
The lymphocyte subset analyses were performed at the Central Laboratory of the Netherlands Red Cross Blood Transfusion Service. We thank Ms W. Dorama, Ms J. Noomen and Ms A. Stevenhagen for assisting in data collection, and K. Bijlsma, C. Verweij, and T.M. Bestebroer for performing the HAI assays.
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The study was approved by the institutional review board of the Leiden University Medical Center.
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Present affiliation, Department of Virology, Erasmus University, Rotterdam, The Netherlands