Enhanced antibody response to pneumococcal polysaccharide vaccine after prior immunization with conjugate pneumococcal vaccine in HIV-infected adults

Abstract

The antibody production by HIV-infected adults after two vaccinations with conjugated pneumococcal vaccine (CPV) and consecutive vaccination with polysaccharide pneumococcal vaccine (PPV) was studied. Thirty days after the second CPV, the geometric mean antibody concentrations (GMC) against pneumococcal polysaccharide serotypes (PPS) 6B, 14 and 19F were significantly lower in the group HIV-infected individuals with <200×10⁶/l CD4⁺ T lymphocytes (group 1) than in the group with ⩾200×10⁶/l CD4⁺ T lymphocytes (group 2) and healthy controls. Thirty days after PPV vaccination the GMC against PPS 6B, 14, 19F and 23F in group 1, and against 6B and 19F in group 2, were significantly lower compared with healthy controls. Both in HIV-infected and in healthy individuals who received CPV and PPV the postvaccination GMC against PPS 14, 19F and 23F were higher compared with historical controls who were not previously immunized with CPV but only received PPV. We conclude that the antibody response to CPV is impaired in HIV-infected individuals. Higher antibody concentrations were achieved in HIV-infected and healthy individuals after sequential vaccination with CPV and PPV compared with PPV vaccination alone.

Introduction

Infections by S. pneumoniae cause severe morbidity and mortality in HIV-infected patients [1], [2], [3], [4], [5], [6], [7], [8]. In several countries it is recommended to vaccinate HIV-infected individuals in order to prevent severe pneumococcal infections [9], [10], [11], [12], [13]. Antibody formation against pneumococcal polysaccharides (PPS) is thought to be a T-lymphocyte-independent process. However, we and others observed that HIV-infected individuals with low CD4⁺ T lymphocytes produce less antibodies against several pneumococcal polysaccharides compared with HIV-infected individuals with normal CD4⁺ T lymphocytes and healthy controls [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24]. After vaccination with pneumococcal polysaccharide vaccine (PPV) the rate of decline of antibody concentrations in HIV-infected individuals is comparable to healthy controls [14], [25], [26]. However, as consequence of the low postvaccination antibody concentrations, within 3 years after vaccination with PPV most HIV-infected individuals will have antibody concentrations below the estimated level required for protection [14].

Newborns and infants up to the age of 2 years of age are unable to produce antibodies to bacterial capsular polysaccharides. In search for more effective vaccines against pneumococcal disease, conjugated pneumococcal vaccines (CPV) have been developed, which induce antibodies in these young children [27]. Polysaccharides conjugated to a protein will induce a T-cell-dependent antibody response. T-cell-dependent vaccines, which unlike T-cell-independent vaccines, are capable of inducing memory T cells and B cells [28], [29]. This latter phenomenon is called priming. A secondary antibody response after earlier vaccination or contact with the respective micro-organism is enhanced by memory cells and probably prolongs the period the vaccinee is protected.

We wanted to investigate in HIV-infected individuals the humoral immune response to T-lymphocyte-dependent CPV, administered twice with an interval of 1 month. Furthermore, we studied whether immunization with CPV primes for a secondary humoral response to immunization with PPV.