Strategies for inducing effective neutralizing antibody responses against HIV-1

Moral-Sánchez, Iván del; Sliepen, Kwinten

doi:10.1080/14760584.2019.1690458

Cited by 26 publications

(30 citation statements)

References 283 publications

(289 reference statements)

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“…However, the Tier-2 NAbs induced by native-like Env trimers usually only neutralize the sequence-matched virus and often target isolate-specific kinks in the glycan shield [8,9,20]. Novel Env antigen designs and immunization strategies are being explored to improve the breadth and potency of these NAb responses and ultimately elicit bNAbs [21].…”

Section: Env As a Broadly Neutralizing Antibody Targetmentioning

confidence: 99%

Nanoparticle Vaccines for Inducing HIV-1 Neutralizing Antibodies

Brinkkemper

Sliepen

2019

Vaccines

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The enormous sequence diversity between human immunodeficiency virus type 1 (HIV-1) strains poses a major roadblock for generating a broadly protective vaccine. Many experimental HIV-1 vaccine efforts are therefore aimed at eliciting broadly neutralizing antibodies (bNAbs) that are capable of neutralizing the majority of circulating HIV-1 strains. The envelope glycoprotein (Env) trimer on the viral membrane is the sole target of bNAbs and the key component of vaccination approaches aimed at eliciting bNAbs. Multimeric presentation of Env on nanoparticles often plays a critical role in these strategies. Here, we will discuss the different aspects of nanoparticles in Env vaccination, including recent insights in immunological processes underlying their perceived advantages, the different nanoparticle platforms and the various immunogenicity studies that employed nanoparticles to improve (neutralizing) antibody responses against Env.

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Section: Env As a Broadly Neutralizing Antibody Targetmentioning

confidence: 99%

Nanoparticle Vaccines for Inducing HIV-1 Neutralizing Antibodies

Brinkkemper

Sliepen

2019

Vaccines

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“…It has been repeatedly reported that the charge of liposome-based vaccines determines their fate (i.e., retention at the point of injection, cellular uptake, and lymph-node trafficking) and the type of immune response they may elicit [ 80 ]. The objectives of particulate display of Env trimers are, inter alia, increased lymph-node trafficking and enhanced B cell engagement [ 2 , 4 , 5 , 6 , 7 , 8 , 9 ]. Although several studies have shown that positively charged liposomes can indeed be delivered to lymph nodes, further research is required to assess whether their use within the context of nanoparticle-based HIV-1 vaccines is indicated/useful at all [ 81 , 82 ].…”

Section: Discussionmentioning

confidence: 99%

“…The reasons for this are multifaceted and have recently been discussed elsewhere [ 2 , 3 ]. The nanoparticulate display of native-like Env trimers and other state-of-the-art HIV immunogens has long been regarded as a promising strategy to improve and shape immune responses [ 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. Liposomes, in particular, have gained wide attention over the last years.…”

Section: Introductionmentioning

confidence: 99%

Conjugation of Native-Like HIV-1 Envelope Trimers onto Liposomes Using EDC/Sulfo-NHS Chemistry: Requirements and Limitations

et al. 2020

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The display of native-like human immunodeficiency virus type 1 envelope (HIV-1 Env) trimers on liposomes has gained wide attention over the last few years. Currently, available methods have enabled the preparation of Env-liposome conjugates of unprecedented quality. However, these protocols require the Env trimer to be tagged and/or to carry a specific functional group. For this reason, we have investigated N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide/N-Hydroxysulfosuccinimide (EDC/Sulfo-NHS) chemistry for its potential to covalently conjugate tag-free, non-functionalized native-like Env trimers onto the surface of carboxyl-functionalized liposomes. The preservation of the liposome’s physical integrity and the immunogen’s conformation required a fine-tuned two-step approach based on the controlled use of β-mercaptoethanol. The display of Env trimers was strictly limited to activated liposomes of positive charge, i.e., liposomes with a positive zeta potential that carry amine-reactive Sulfo-NHS esters on their surface. In agreement with that, conjugation was found to be highly ionic strength- and pH-dependent. Overall, we have identified electrostatic pre-concentration (i.e., close proximity between negatively charged Env trimers and positively charged liposomes established through electrostatic attraction) to be crucial for conjugation reactions to proceed. The present study highlights the requirements and limitations of potentially scalable EDC/Sulfo-NHS-based approaches and represents a solid basis for further research into the controlled conjugation of tag-free, non-functionalized native-like Env trimers on the surface of liposomes, and other nanoparticles.

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“…Most current efforts are aimed at inducing broadly neutralizing antibodies (bNAbs), which can neutralize the majority of HIV strains. The ability of bNAbs to neutralize a wide spectrum of HIV strains (broad cross-reactivity) is a major advantage (14). Moreover, the safety and remarkable antiviral activity of highly potent HIV specific bNAbs have been demonstrated in preclinical and clinical trials (15).…”

Section: Challenges In Hiv Vaccine Developmentmentioning

confidence: 99%

Major Scientific Hurdles in HIV Vaccine Development: Historical Perspective and Future Directions

2020

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Following the discovery of HIV as a causative agent of AIDS, the expectation was to rapidly develop a vaccine; but thirty years later, we still do not have a licensed vaccine. Progress has been hindered by the extensive genetic variability of HIV and our limited understanding of immune responses required to protect against HIV acquisition. Nonetheless, valuable knowledge accrued from numerous basic and translational science research studies and vaccine trials has provided insight into the structural biology of the virus, immunogen design and novel vaccine delivery systems that will likely constitute an effective vaccine. Furthermore, stakeholders now appreciate the daunting scientific challenges of developing an effective HIV vaccine, hence the increased advocacy for collaborative efforts among academic research scientists, governments, pharmaceutical industry, philanthropy, and regulatory entities. In this review, we highlight the history of HIV vaccine development efforts, highlighting major challenges and future directions.

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Strategies for inducing effective neutralizing antibody responses against HIV-1

Cited by 26 publications

References 283 publications

Nanoparticle Vaccines for Inducing HIV-1 Neutralizing Antibodies

Nanoparticle Vaccines for Inducing HIV-1 Neutralizing Antibodies

Conjugation of Native-Like HIV-1 Envelope Trimers onto Liposomes Using EDC/Sulfo-NHS Chemistry: Requirements and Limitations

Major Scientific Hurdles in HIV Vaccine Development: Historical Perspective and Future Directions

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