[Immunization against the human immunodeficiency virus in Zaire]

Area of Science:

• Immunology
• Virology
• Vaccine Development

Context:

• The first human immunizations against the Human Immunodeficiency Virus type 1 (HIV-1) began in 1986 using a vaccinia virus recombinant (V25) expressing HIV-1 envelope glycoproteins.
• Initial priming with V25 in HIV-seronegative volunteers induced only a weak immune response, necessitating further investigation into effective boosting strategies.

Purpose:

• To evaluate different boosting protocols to enhance the immune response initiated by V25 priming in HIV-1 vaccine candidates.
• To assess the efficacy of various boosting methods in generating both cell-mediated immunity (CMI) and humoral immunity, including neutralizing antibodies.

Summary:

• Four distinct boosting protocols were tested following V25 priming: intravenous infusion of fixed infected cells, repeated scarification with V25, scarification with Gp 120 fragments, and intramuscular injection of purified cell membranes infected with V25.
• While three protocols showed minimal enhancement of CMI and low neutralizing antibody titers, boosting with fixed V25-infected autologous cells in one individual (D.Z.) elicited a robust group-specific anamnestic immune response.
• This successful boost resulted in high levels of antibodies against the viral envelope, significant neutralizing antibodies against diverse HIV-1 strains, enhanced group-specific CMI, and strong delayed-type hypersensitivity to Gp 160.

Impact:

• Demonstrates the potential for achieving a significant immune response against HIV-1 in humans through optimized vaccination strategies.
• Highlights the effectiveness of using fixed, infected autologous cells as a boosting agent for eliciting potent humoral and cellular immunity against HIV-1.
• Provides crucial insights into the development of effective HIV-1 vaccines, particularly regarding the induction of neutralizing antibodies and cell-mediated immunity.