Long-term follow-up: no effect of therapeutic vaccination with HIV-1 p17/p24:Ty virus-like particles on HIV-1 disease progression

Lindenburg, Catharina E. A.; Stolte, Ineke G.; Langendam, Miranda; Miedema, Frank; Williams, Ian; Colebunders, Robert; Weber, Jonathan; Fisher, Martin; Coutinho, Roel A.

doi:10.1016/s0264-410x(02)00102-0

Cited by 32 publications

(17 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While therapeutic vaccination holds promise for enhancing the control of chronic infections (4), the efficacy of this approach has been disappointing in many situations (9,22,28,40). In this study, we have begun to examine the potential of therapeutic vaccination to alter the course of chronic infection and the possible limitations associated with poor responses to this type of therapeutic intervention.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have examined the potential benefits of therapeutic vaccination during a variety of persistent infections (6,9,15,18,20,22,24,28,30,31,38,40). On one hand, some reports have demonstrated enhanced immune responses following therapeutic vaccination.…”

mentioning

confidence: 99%

“…On the other hand, the vaccination of SIV-infected animals that were not treated with HAART resulted in minimal boosting of T-cell responses (15). In addition, a variety of other studies have found a minimal efficacy of therapeutic vaccination during persistent infection (9,22,28,40). While several different systems and methods of therapeutic vaccination have been used, the mechanistic basis for positive effects observed in some studies but not in others remains incompletely understood.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Low CD8 T-Cell Proliferative Potential and High Viral Load Limit the Effectiveness of Therapeutic Vaccination

Wherry

Blattman

Ahmed

2005

J Virol

106

View full text Add to dashboard Cite

Therapeutic vaccination has the potential to boost immune responses and enhance viral control during chronic infections. However, many therapeutic vaccination approaches have fallen short of expectations, and effective boosting of antiviral T-cell responses is not always observed. To examine these issues, we studied the impact of therapeutic vaccination, using a murine model of chronic infection with lymphocytic choriomeningitis virus (LCMV). Our results demonstrate that therapeutic vaccination using a recombinant vaccinia virus expressing the LCMV GP33 CD8 T-cell epitope can be effective at accelerating viral control. However, mice with lower viral loads at the time of vaccination responded better to therapeutic vaccination than did those with high viral loads. Also, the proliferative potential of GP33-specific CD8 T cells from chronically infected mice was substantially lower than that of GP33-specific memory CD8 T cells from mice with immunity to LCMV, suggesting that poor T-cell expansion may be an important reason for suboptimal responses to therapeutic vaccination. Thus, our results highlight the potential positive effects of therapeutic vaccination on viral control during chronic infection but also provide evidence that a high viral load at the time of vaccination and the low proliferative potential of responding T cells are likely to limit the effectiveness of therapeutic vaccination.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Low CD8 T-Cell Proliferative Potential and High Viral Load Limit the Effectiveness of Therapeutic Vaccination

Wherry

Blattman

Ahmed

2005

J Virol

106

View full text Add to dashboard Cite

show abstract

“…Concordantly, specific increase of solely anti-p24 responses as achieved in vaccination with diverse p24 antigen regimens has not shown clinical benefits. [26][27][28][29][30][31][32][33][34][35] Hence, the boost in reactivites to p24 observed here likely reflects the capacity of the immune system to react to antigenic challenge and is not a direct correlate of protection. Previous studies on the prognostic value of antibodies to p24 measured absolute antibody levels at a specific time point and sought to derive associations with disease progression from these values.…”

Section: Discussionmentioning

confidence: 99%

Humoral immunity to HIV-1: kinetics of antibody responses in chronic infection reflects capacity of immune system to improve viral set point

Trkola¹

2004

Blood

View full text Add to dashboard Cite

We analyzed the humoral immune response in 46 patients following structured treatment interruption (STI) to investigate the general potential of therapeutic vaccination in chronic HIV-1 infection. Evoked antibody titer increases to glycoprotein 120 (gp120) and p24 were low during 4 short-term STIs and only reached significance during a fifth long-term interruption. Although induction of binding antibodies to viral antigens was not associated with potent suppression of viremia, we observed that individuals with a rapid and high response to p24, and to a lesser extent also to gp120, lowered their viral set points significantly. Of note, the increase of the anti-p24 response correlated with specific CD4 T helper frequency to this antigen. Despite induction of binding antibody responses, which correlated with improved viral control, the increase in neutralizing activity was marginal and did not lead to this enhanced viral suppression. However, a subgroup of patients who potently suppressed viremia independently of STI had significantly higher pre-existing neutralization titers, suggesting a role of humoral immunity in conferring potent protection. In summary, measuring the kinetics of antibody responses provided a marker to validate the responsiveness and capacities of the immune system of HIV-1-infected individuals and reflected the patients' ability to decrease viral set points.

show abstract

“…In part this is due to some high profile disappointing results for VLP vaccines in the early stages of development, for example an ineffective early vaccine for HIV based on Ty VLPs. 72 This example raises a point of caution for VLP vaccine designers. In general, VLPs stimulate efficient cellular and humoral immune responses but, as with any vaccine, they rely on the long term host response to be effective.…”

Section: Perspectives: Myths and Factsmentioning

confidence: 99%

Virus‑like particles as a vaccine delivery system: Myths and facts

Roy¹,

Noad²

2008

Human Vaccines

151

View full text Add to dashboard Cite

Vaccines against viral disease have traditionally relied on attenuated virus strains or inactivation of infectious virus. Subunit vaccines based on viral proteins expressed in heterologous systems have been effective for some pathogens, but have often suffered from poor immunogenicity due to incorrect protein folding or modification. In this review we focus on a specific class of viral subunit vaccine that mimics the overall structure of virus particles and thus preserves the native antigenic conformation of the immunogenic proteins. These virus-like particles (VLPs) have been produced for a wide range of taxonomically and structurally distinct viruses, and have unique advantages in terms of safety and immunogenicity over previous approaches. With new VLP vaccines for papillomavirus beginning to reach the marketplace we argue that this technology has now 'come-of-age' and must be considered a viable vaccine strategy.

show abstract

Long-term follow-up: no effect of therapeutic vaccination with HIV-1 p17/p24:Ty virus-like particles on HIV-1 disease progression

Cited by 32 publications

References 24 publications

Low CD8 T-Cell Proliferative Potential and High Viral Load Limit the Effectiveness of Therapeutic Vaccination

Low CD8 T-Cell Proliferative Potential and High Viral Load Limit the Effectiveness of Therapeutic Vaccination

Humoral immunity to HIV-1: kinetics of antibody responses in chronic infection reflects capacity of immune system to improve viral set point

Virus‑like particles as a vaccine delivery system: Myths and facts

Contact Info

Product

Resources

About