Immunization with both T cell-dependent and T cell-independent vaccines augments HIV viral load secondarily to stimulation of tumor necrosis factor alpha.
Vaccination of HIV-infected individuals increases HIV viral load, reduces CD4 cell counts, and might influence disease progression. Because these deleterious effects are postulated to be secondary to a direct activation of T lymphocytes induced by the immunogen, we compared immunologic and virologic effects of a T cell-dependent and a T cell-independent vaccine. Seventeen HIV-infected children were immunized with influenza (FLU) (T cell-dependent) or pneumococcal (PNEUMO) (T cell-independent) vaccines. HIV viral load and type 1 (IL-2 and IFN-gamma) and type 2 (IL-4 and IL-10) cytokine production were evaluated before and 7, 14, and 28 days after vaccination. Slopes of CD4 cell counts analyzed 6 months before and 6 months after vaccination were not significantly different. HIV viral load increased in both groups of children despite the fact that type 1 cytokine production and the type 1-to-type 2 ratio increased in FLU-vaccinated but not in PNEUMO-vaccinated patients. Thus, an increase in HIV viral load in the absence of T cell activation (as measured by cytokine production) was observed in PNEUMO-vaccinated children. Because polysaccharides of the bacterial cell wall stimulate TNF-alpha production by monocyte-macrophages and TNF-alpha was shown to stimulate HIV replication directly on activation of NF-kappa b after binding the long terminal repeat (LTR) sequences of HIV, we measured TNF-alpha production and observed a significant increase in both groups of vaccines. These data suggest that an increase in HIV viral load can be observed in vaccinated HIV-infected children even independent of direct antigen-induced activation of T lymphocytes, and that augmented production of TNF-alpha might play a role in this phenomenon.
Viganò
A
A
Cattedra di Pediatria IV, Università degli Studi di Milano, Ospedale Luigi Sacco, Milan, Italy.
Bricalli
D
D
Trabattoni
D
D
Salvaggio
A
A
Ruzzante
S
S
Barbi
M
M
Di Sanzo
G
G
Principi
N
N
Clerici
M
M
D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis; D006678:HIV / Q000276:immunology / Q000502:physiology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets; D012367:RNA, Viral / Q000097:blood; D013296:Streptococcus pneumoniae / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014611:Vaccination; D019562:Viral Load; D014766:Viremia
D001428:Bacterial Vaccines; D016207:Cytokines; D007252:Influenza Vaccines; D008070:Lipopolysaccharides; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha