mRNA-encoded HIV-1 Env trimer ferritin nanoparticles induce monoclonal antibodies that neutralize heterologous HIV-1 isolates in mice

Mu, Zekun; Wiehe, Kevin; Saunders, Kevin O.; Henderson, Rory; Cain, Derek W.; Parks, Robert; Martik, Diana; Mansouri, Katayoun; Edwards, Robert J.; Newman, Amanda; Lu, Xiaozhi; Xia, Shi-Mao; Eaton, Amanda; Bonsignori, Mattia; Montefiori, David C.; Han, Qingmei; Venkatayogi, Sravani; Evangelous, Tyler; Wang, Yunfei; Rountree, Wes; Korber, Bette; Wagh, Kshitij; Tam, Ying K.; Barbosa, Christopher J.; Alam, S. Munir; Williams, Wilton B.; Tian, Ming; Alt, Frederick W.; Pardi, Norbert; Weissman, Drew; Haynes, Barton F.

doi:10.1016/j.celrep.2022.110514

Cited by 38 publications

(32 citation statements)

References 75 publications

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“…In this context, the use of an mRNA-based vaccine offers new perspectives, accelerating the HIV research field by facilitating the design of new potent antigens and empowering the cellular and antibody immune responses [ 30 ]. Indeed, mRNA prophylactic tools have already shown comparable polyfunctional antibody responses to proteins in nonhuman primates [ 31 ], and other studies have confirmed the ability to elicit tier 2 neutralizing antibodies able to reduce the risk of heterologous infections [ 32 , 33 , 34 ]. Those preclinical successes permitted the National Institute of Allergy and Infectious diseases to launch three experimental HIV vaccine clinical trials in 2022 (NCT05217641).…”

Section: Introductionmentioning

confidence: 99%

DLin-MC3-Containing mRNA Lipid Nanoparticles Induce an Antibody Th2-Biased Immune Response Polarization in a Delivery Route-Dependent Manner in Mice

et al. 2023

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mRNA-based vaccines have made a leap forward since the SARS-CoV-2 pandemic and are currently used to develop anti-infectious therapies. If the selection of a delivery system and an optimized mRNA sequence are two key factors to reach in vivo efficacy, the optimal administration route for those vaccines remains unclear. We investigated the influence of lipid components and immunization route regarding the intensity and quality of humoral immune responses in mice. The immunogenicity of HIV-p55Gag encoded mRNA encapsulated into D-Lin-MC3-DMA or GenVoy-ionizable lipid-based LNPs was compared after intramuscular or subcutaneous routes. Three sequential mRNA vaccines were administrated followed by a heterologous boost composed of p24-HIV protein antigen. Despite equivalent IgG kinetic profiles of general humoral responses, IgG1/IgG2a ratio analysis showed a Th2/Th1 balance toward a Th1-biased cellular immune response when both LNPs were administrated via the intramuscular route. Surprisingly, a Th2-biased antibody immunity was observed when DLin-containing vaccine was injected subcutaneously. A protein-based vaccine boost appeared to reverse this balance to a cellular-biased response correlated to an increase in antibody avidity. Our finding suggests that the intrinsic adjuvant effect of ionizable lipids appears to be dependent on the delivery route used, which could be relevant to reach potent and long-lasting immunity after mRNA-based immunization.

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Section: Introductionmentioning

confidence: 99%

DLin-MC3-Containing mRNA Lipid Nanoparticles Induce an Antibody Th2-Biased Immune Response Polarization in a Delivery Route-Dependent Manner in Mice

et al. 2023

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“…In mice, a conjugated protein nanoparticle vaccine elicited a similar broadly reactive antibody response while eliciting fewer off‐target, non‐neutralizing antibodies 102 . Saunders also showed that an mRNA‐LNP vaccine, in which the mRNA encodes HIV ENV, can successfully lead to assembled protein nanoparticles in vitro and elicit neutralizing antibodies in mice 103 …”

Section: Protein Nanoparticle Vaccinesmentioning

confidence: 99%

“…102 Saunders also showed that an mRNA-LNP vaccine, in which the mRNA encodes HIV ENV, can successfully lead to assembled protein nanoparticles in vitro and elicit neutralizing antibodies in mice. 103…”

Section: Nanoparticle Vaccines To Elicit Broadly Reactive Anti-hiv Re...mentioning

confidence: 99%

Progress in vaccine development for infectious diseases—a Keystone Symposia report

Cable¹,

Graham

Koup

et al. 2023

Annals of the New York Academy of Sciences

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The COVID‐19 pandemic has taught us many things, among the most important of which is that vaccines are one of the cornerstones of public health that help make modern longevity possible. While several different vaccines have been successful at stemming the morbidity and mortality associated with various infectious diseases, many pathogens/diseases remain recalcitrant to the development of effective vaccination. Recent advances in vaccine technology, immunology, structural biology, and other fields may yet yield insight that will address these diseases; they may also help improve societies’ preparedness for future pandemics. On June 1–4, 2022, experts in vaccinology from academia, industry, and government convened for the Keystone symposium “Progress in Vaccine Development for Infectious Diseases” to discuss state‐of‐the‐art technologies, recent advancements in understanding vaccine‐mediated immunity, and new aspects of antigen design to aid vaccine effectiveness.

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“…These ferritin nanoparticles elicited antigen‐specific germinal center and memory B cells as well as T follicular helper cells. Additionally, in DH270 KI mice, V3‐glycan bnAb N332 supersite‐dependent neutralizing antibodies capable of tier 2 autologous neutralization were generated (Mu et al, 2022). mRNA‐LNPs encoding ferritin‐based nanovaccines have also been utilized for SARS‐CoV‐2 prophylaxis.…”

Section: De Novo Assembly Of Nanovaccinesmentioning

confidence: 99%

Gene‐encoded nanoparticle vaccine platforms for in vivo assembly of multimeric antigen to promote adaptive immunity

Tursi

Kulp

et al. 2023

WIREs Nanomed Nanobiotechnol

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Nanoparticle vaccines are a diverse category of vaccines for the prophylaxis or treatment of various diseases. Several strategies have been employed for their optimization, especially to enhance vaccine immunogenicity and generate potent B-cell responses. Two major modalities utilized for particulate antigen vaccines include using nanoscale structures for antigen delivery and nanoparticles that are themselves vaccines due to antigen display or scaffolding-the latter of which we will define as "nanovaccines." Multimeric antigen display has a variety of immunological benefits compared to monomeric vaccines mediated through potentiating antigen-presenting cell presentation and enhancing antigen-specific B-cell responses through B-cell

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mRNA-encoded HIV-1 Env trimer ferritin nanoparticles induce monoclonal antibodies that neutralize heterologous HIV-1 isolates in mice

Cited by 38 publications

References 75 publications

DLin-MC3-Containing mRNA Lipid Nanoparticles Induce an Antibody Th2-Biased Immune Response Polarization in a Delivery Route-Dependent Manner in Mice

DLin-MC3-Containing mRNA Lipid Nanoparticles Induce an Antibody Th2-Biased Immune Response Polarization in a Delivery Route-Dependent Manner in Mice

Progress in vaccine development for infectious diseases—a Keystone Symposia report

Gene‐encoded nanoparticle vaccine platforms for in vivo assembly of multimeric antigen to promote adaptive immunity

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