Biology subjects

Francian, A.

Publications and source records attributed to Francian, A..

5 recordsLinked to original sources

bioRxiv2025

A Comparative Evaluation of Adjuvants for Enhancing Antibody Responses to a Nanoparticle-Based Malaria Vaccine

Effective pre-erythrocytic Plasmodium falciparum vaccines targeting circumsporozoite protein (CSP) must elicit strong and durable antibody responses. We assessed the ability of different classes of adjuvants to enhance immunity of a promising CSP-epitope-targeted virus-like particle (VLP)-based vaccine. Five formulations significantly increased anti-CSP IgG titers and several also enhanced antibody durability. This study identifies promising adjuvants that enhance both the magnitude and longevity of VLP-induced immunity.

immunology↗

bioRxiv2025

Immunization with VLP-based vaccines induces high IgG antibody titers in dermal interstitial fluid

Although antibodies often exert their effects within the interstitium, the distribution of antibodies within extravascular tissue compartments is not typically measured. Here, IgG titers in peripheral blood and dermal interstitial fluid (ISF) were compared after intramuscular and intradermal immunization with virus-like particle (VLP)-based vaccines. Antibody titers and durability in serum and ISF were similar, indicating that VLP-based vaccines can efficiently elicit strong antibody responses in the skin.

immunology↗

bioRxiv2025

Virus-like particle vaccines targeting a key epitope in circumsporozoite protein provide sterilizing immunity against malaria in a mouse challenge model

Vaccines that target the pre-erythrocytic stage of the malaria lifecycle have the potential to provide sterilizing immunity but must elicit sustained, high-titer antibody responses to completely prevent infection. Most pre-erythrocytic vaccines target circumsporozoite protein (CSP), the major surface antigen on Plasmodium falciparum sporozoites. Antibodies targeting distinct epitopes within the central repeat region of CSP have the potential to provide protection from infection, but we have focused on developing vaccines that target a highly vulnerable CSP epitope that is targeted by the potent monoclonal antibody L9. In a previous study, we produced a pre-erythrocytic vaccine displaying a synthetic peptide representing the L9 epitope on Q{beta} bacteriophage virus-like particles (VLPs). This vaccine elicited strong anti-CSP antibody responses that protected mice from malaria challenge. Here, we asked whether the structural context of the L9 epitope influences the quality of antibody responses. We compared the immunogenicity and protective efficacy of Q{beta} L9 VLPs to recombinant VLPs that display the L9 peptide in a structure that is hypothesized to mimic its native conformation. Recombinant MS2 bacteriophage VLPs displaying various lengths of the L9 epitope were produced and immunogenicity and protective efficacy were evaluated in mice. Our results demonstrate that MS2 L9 VLPs, particularly those displaying longer L9 peptides and in combination with a potent novel adjuvant, elicit strong and durable antibody responses that lower malaria liver burden and prevent infection. We also compared the efficacy of L9-targeted vaccines to the licensed vaccine, RTS,S/AS01E (Mosquirix, GSK). Immunization with Q{beta} L9 VLPs, MS2 L9 VLPs, and RTS,S/AS01E provided significant protection from liver-stage infection in a mouse model; immunization with Q{beta} L9 VLPs elicited sterilizing immunity in the highest percentage of mice. A combination vaccine consisting of MS2 L9 and Q{beta} L9 VLPs, each presenting the L9 epitope in distinct structural forms, provided the strongest protection, reducing liver parasite burden and promoting sterilizing immunity more effectively than the licensed RTS,S/AS01E vaccine.

immunology↗

bioRxiv2024

Formulation, Characterization, and in vivo Immunogenicity of Heat-Stabilized Dissolvable Microneedles Containing a Novel VLP Vaccine

Since its introduction, vaccination has heavily improved health outcomes. However, implementing vaccination efforts can be challenging, particularly in low and middle-income countries with warmer climates. Microneedle technology has been developed for its simple and relatively painless applications of vaccines. However, no microneedle vaccine has yet been approved by the FDA. A few hurdles must be overcome, including the need to evaluate the safety and biocompatibility of the polymer used to fabricate these microneedles. Additionally, it is important to demonstrate reliable immune responses comparable to or better than those achieved through traditional administration routes. Scalability in manufacturing and the ability to maintain vaccine potency during storage and transportation are also critical factors. In this study, we developed vaccine-loaded dissolvable microneedles that showed preclinical immunogenicity after storage in extreme conditions. We developed our microneedles using the conventional micromolding technique with polyacrylic acid (PAA) polymer, incorporating a novel virus-like particle (VLP) vaccine targeting arboviruses. We performed characterization studies on these microneedles to assess needle sharpness, skin insertion force, and VLP integrity. We also investigated the thermostability of the vaccine after storing the microneedles at elevated temperatures for approximately 140 days. Finally, we evaluated the immunogenicity of this vaccine in mice, comparing transdermal (microneedle) with intramuscular (hypodermic needle) administration. We successfully fabricated and characterized VLP-loaded microneedles that could penetrate the skin and maintain vaccine integrity even after exposure to extreme storage conditions. These microneedles also elicited robust and long-lasting antibody responses similar to those achieved with intramuscular administration.

bioengineering↗

bioRxiv2024

Virus-like particle-based vaccines targeting the Anopheles mosquito salivary protein, TRIO

Malaria is a highly lethal infectious disease caused by Plasmodium parasites. These parasites are transmitted to vertebrate hosts when mosquitoes of the Anopheles genus probe for a blood meal. Sporozoites, the infectious stage of Plasmodium, transit to the liver within hours of injection into the dermis. Vaccine efforts are hindered by the complexity of the parasites lifecycle and the speed at which the infection is established in the liver. In an effort to enhance immunity against Plasmodium, we produced a virus-like particle (VLP)-based vaccine displaying an epitope of TRIO, an Anopheles salivary protein which has been shown to enhance mobility and dispersal of sporozoites in the dermis. Previous work demonstrated that passive immunization with TRIO offered protection from liver infection and acted synergistically with a Plasmodium targeted vaccine. Immunization of mice with TRIO VLPs resulted in high-titer and long-lasting antibody responses that did not significantly drop for over 18 months post-immunization. TRIO VLPs were similarly immunogenic when combined with an anti-malaria vaccine targeting the L9 epitope of the Plasmodium falciparum circumsporozoite protein.However, when used in a malaria challenge mouse model, TRIO VLPs only provided modest protection from infection and did not boost the protection provided by L9 VLPs.

immunology↗