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HIV pseudovirion vaccine exposing Env "fusion intermediates"-response to immunisation in human CD4/CCR5-transgenic
Valerie Bosch1, Tanya Pfeiffer, Gerard Devitt
1Forschungsschwerpunkt Infektion und Krebs, F020, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany. V.Bosch@dkfz.de
Immune responses to a pseudovirion-based HIV vaccine enriched in Env conformations, which have been induced to an authentic intermediate fusion stage by interaction with the cellular HIV receptor complex, have been analysed in human CD4/CCR5-transgenic rats. High titre Env-binding antibodies were elicited. However, these immune sera failed to neutralise HIV-1, but rather led to an enhancement of infection in vitro. This enhancing activity appeared to be directed towards contaminating cellular proteins in the vaccine and was able to mask neutralisation of potent, mixed-in neutralising antibodies. The induced Env-specific antibodies, purified on the basis of binding to monomeric Env, retained high-binding activity, but failed to be neutralising. Thus, it remains unclear whether vaccines based on induced HIV Env fusion intermediates can elicit broadly neutralising responses.
Immune responses to a pseudovirion-based HIV vaccine enriched in Env conformations, which have been induced to an authentic intermediate fusion stage by interaction with the cellular HIV receptor complex, have been analysed in human CD4/CCR5-transgenic rats. High titre Env-binding antibodies were elicited. However, these immune sera failed to neutralise HIV-1, but rather led to an enhancement of infection in vitro. This enhancing activity appeared to be directed towards contaminating cellular proteins in the vaccine and was able to mask neutralisation of potent, mixed-in neutralising antibodies. The induced Env-specific antibodies, purified on the basis of binding to monomeric Env, retained high-binding activity, but failed to be neutralising. Thus, it remains unclear whether vaccines based on induced HIV Env fusion intermediates can elicit broadly neutralising responses.
