Abstract
Immunotherapy aims to assist the natural immune system in achieving control over viral infection. Various immunotherapy formats have been evaluated in either therapy-naive or therapy-experienced HIV-infected patients over the last 20 years. These formats included non-antigen specific strategies such as cytokines that stimulate immunity or suppress the viral replication, as well as antibodies that block negative regulatory pathways. A number of HIV-specific therapeutic vaccinations have also been proposed, using in vivo injection of inactivated virus, plasmid DNA encoding HIV antigens, or recombinant viral vectors containing HIV genes. A specific format of therapeutic vaccines consists of ex vivo loading of autologous dendritic cells with one of the above mentioned antigenic formats or mRNA encoding HIV antigens.This review provides an extensive overview of the background and rationale of these different therapeutic attempts and discusses the results of trials in the SIV macaque model and in patients. To date success has been limited, which could be explained by insufficient quality or strength of the induced immune responses, incomplete coverage of HIV variability and/or inappropriate immune activation, with ensuing increased susceptibility of target cells.Future attempts at therapeutic vaccination should ideally be performed under the protection of highly active antiretroviral drugs in patients with a recovered immune system. Risks for immune escape should be limited by a better coverage of the HIV variability, using either conserved or mosaic sequences. Appropriate molecular adjuvants should be included to enhance the quality and strength of the responses, without inducing inappropriate immune activation. Finally, to achieve a long-lasting effect on viral control (i.e. a “functional cure”) it is likely that these immune interventions should be combined with anti-latency drugs and/or gene therapy.
Highlights
Immunotherapy aims to assist the natural immune system in achieving control over viral infection
No virological parameters could be measured because patients did not undergo analytical treatment interruption (ATI), we showed that the CD8 T cells from the vaccines could inhibit superinfection of autologous CD4 T cells with vaccine related IIIB virus in vitro [111]
Amongst the non-antigen-specific immune approaches, systemic IL-2 has been exhaustively investigated and was shown not to provide clinical benefit in addition to Highly Activate Antiretroviral Therapy” (HAART). It remains to be seen whether systemic use of other common γ chain cytokines, such as IL-7 or IL-21, could be useful for particular indications
Summary
Tendency lower viral rebound after ATI but not significant. Vaccinated animals had higher CD4 T cell [94] counts, SIV-specific cell-mediated immunity and anti-SIV-neutralizing antibodies. After ATI there was a sustained reduction in VL and increased CD4 T cell responses. Increased T cell responses no effect on [98] viral rebound. Well tolerated and no effect on viral load. Discontinuation of HAART after vaccination failed to lower viral set points. SIV-specific CD4 and CD8T cell responses during antiretroviral cover and off treatment. Effective and durable SIV-specific cellular and humoral immunity is elicited. Plasma viral load levels were decreased by 80% (median) over the first 112 days following immunization. Partial viral control 24 weeks after ATI. Modest decrease in viral load 24 weeks after first vaccination compared to controls
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
