An experimental prime-boost regimen leading to HIV type 1-specific mucosal and systemic immunity in BALB/c mice.

Induction of mucosal as well as systemic immunity to HIV-1 is considered to have high priority in current concepts of future AIDS vaccines. Here we show that the desired immune responses can be elicited by an experimental prime-boost regimen consisting of mucosal (intragastric) application of a recombinant vaccinia virus carrying the HIV-1 env gene (vSC25), followed by parenteral (intradermal) immunization with the recombinant HIV-1 glycoprotein 160 (rgp160). Following intragastric immunization of mice with vSC25 in combination with the mucosal adjuvant cholera toxin (CT), HIV-1 env-specific IgA was secreted by B cells of Peyer's patches and the lamina propria. Moreover, mucosal (intragastric and intranasal) application of vSC25 (both in presence or absence of CT) induced a long-lasting, HIV-1 env-specific systemic cytotoxic T cell response. Subsequent intradermal boosters with rgp160 led to HIV-1-specific T cell memory and serum antibodies.

Allostimulated lymphocytes inhibit replication of HIV type 1.

Previous reports demonstrated that alloantigen- or xenoantigen-specific antibodies displayed neutralizing activity toward human or simian immunodeficiency viruses. In the present article we have addressed the question of alloantigen-induced cell-mediated anti-HIV activity. We show that allostimulation resulted in a lymphocyte population (largely of the CD8-positive phenotype) with the capacity to inhibit HIV-1 replication in PHA blasts of homologous and, unexpectedly, also autologous origin. The allostimulated effector cells exerted their activity via a noncytolytic mechanism. Experiments in which direct cell-to-cell contact between allostimulated effectors and HIV-1-infected PHA blasts was prevented by a semipermeable membrane indicated that soluble mediators were involved in inhibition of HIV-1 replication. As such allostimulated effectors not only would have the capacity to prevent viral replication in allogeneic HIV-1-infected cells (known to play an important role in HIV-1 transmission in vivo), but also might inhibit HIV-1 growth in autologous lymphocytes, the concept of an AIDS vaccine containing both HIV-1 antigens and alloantigens warrants further consideration.

Humoral and cell-mediated immunity to vero cell-derived influenza vaccine.

A candidate trivalent influenza whole virus vaccine produced in a continuous mammalian cell line (Vero), and analogous commercially available egg-derived vaccines, were compared for their ability to induce humoral and cell-mediated immunity in Balb/c mice. Substantial haemagglutination-inhibition titre and high levels of influenza virus-specific IgG were found in all groups of immunized mice, irrespective of the vaccine formulation. The IgG responses were predominantly of IgG1 and IgG2a/2b isotypes. Virus-specific secretory IgA antibodies were detected only in mice immunized intranasally with a live virus, derived either from Vero cells or eggs. T-cell proliferative responses and T-helper 1 type cytokine release was significantly higher in mice immunized with Vero cell-derived influenza vaccine compared to egg-derived vaccine formulations. We have demonstrated that the immunogenicity of the trivalent Vero cell-derived whole influenza virus vaccine was comparable to that of the equivalent egg-derived vaccine, with respect to humoral immune response and was superior with respect to cellular response.

Humoral and cellular immunity induced by antigens adjuvanted with colloidal iron hydroxide.

The immunopotentiating activities of colloidal iron hydroxide, a novel, experimental mineral adjuvant, and of aluminium hydroxide. the licensed adjuvant for human vaccines, were compared. Our studies revealed that colloidal iron hydroxide and aluminium hydroxide behaved comparably with respect to supporting induction of an antibody response to tetanus toxoid. Furthermore, mice immunized with both, the experimental vaccine (tick-borne encephalitis virus (TBEV) antigen adsorbed to colloidal iron hydroxide) or with a commercially available TBEV vaccine (adjuvanted with aluminium hydroxide), developed long-lasting antibody responses which protected the animals from TBEV infection even one year after vaccination. The use of colloidal iron hydroxide as adjuvant had the additional advantage to reproducibly support induction of HIV-1 envelope-specific cytotoxic T lymphocytes (CTL), when used as adjuvant for a HIV-1 env-carrying recombinant fowlpox virus and being applied via the subcutaneous route. Aluminium hydroxide was much less active in this respect. Non-adjuvanted recombinant fowlpox elicited CTLs only when given intravenously or intraperitoneally, vaccination routes considered not to be suitable for routine use in humans. Further studies to evaluate the use of colloidal iron as possible alternative and/or supplement for routinely used mineral adjuvants may therefore be warranted.