Product Citations: 24

Induction of systemic and mucosal immune response against Zika virus by vaccination with non-infectious chimeric VLPs.

In Scientific Reports on 10 July 2025 by Fassola, L. A., Rupil, L. L., et al.

The Zika virus (ZIKV) causes acute febrile illness and can lead to complications such as Guillain-Barré syndrome and congenital disorders. As arbovirus outbreaks increase, vaccination becomes a crucial preventive strategy. Currently, no commercial vaccines are available for ZIKV, which is transmitted by mosquitoes and bodily fluids, underscoring the need for a safe vaccine that induces both systemic and mucosal immune responses. In this study, we present a ZIKV vaccine candidate utilizing virus-like particles (VLPs) technology combined with variant-specific surface proteins (VSP) from Giardia lamblia. Previous research demonstrated that these VSP act as effective adjuvants and are resistant to gastrointestinal degradation, expanding administration possibilities via orogastric routes in addition to the conventional subcutaneous route. To develop the immunogen, we engineered retrovirus-derived VLPs decorated with the ZIKV envelope glycoprotein (ZIKV-E) as the target antigen, incorporating VSPs on their surface. Immunocompetent Balb/c mice were immunized with VSP-VLPs ZIKV-E via oral and subcutaneous routes. Immune characterization revealed robust systemic and mucosal humoral responses, as well as a specific cellular activation. Moreover, a significant neutralizing capacity of serum antibodies was observed. These findings highlight the potential of the vaccine candidate to elicit a targeted immune response, achieved through different administration methods.
© 2025. The Author(s).

  • Immunology and Microbiology

Maternal immunity protects offspring from enteric viral infection without negatively affecting humoral immune memory

Preprint on BioRxiv : the Preprint Server for Biology on 24 September 2024 by Muleta, K. G., Pærregaard, S. I., et al.

ABSTRACT Passive transfer of antibodies can effectively protect newborns from dysbiosis and infection but has also been proposed to inhibit intrinsic immune onset in the protected child. Yet, some early childhood vaccines are highly efficacious despite the presence of maternal antibodies. We here used a murine neonatal Rotavirus (RV) infection model in combination with cross-foster approaches to dissect the role that milk-derived antibodies play in the long-term induction of pup-intrinsic immunity. We found that milk-derived RV-specific antibodies efficiently protect from RV infection. While the occurrence of RV-specific IgA-producing plasma cells is temporarily blunted, maternally protected pups do mount delayed protective humoral immunity after weaning. Fate-mapping of pre-existing B cells revealed that the RV-specific plasma cell pool originates from B cells imprinted at the time of virus exposure regardless of maternal protection. Our data challenges the dogma that maternal antibody is inhibitory and instead permits safe and efficacious immune education in the growing organism.

  • Immunology and Microbiology

A modular self-assembling and self-adjuvanting multiepitope peptide nanoparticle vaccine platform to improve the efficacy and immunogenicity of BCG

Preprint on BioRxiv : the Preprint Server for Biology on 5 August 2024 by Zhao, G., Sathkumara, H. D., et al.

After more than a century since its initial development, Bacille Calmette-Guérin (BCG) remains the only licensed vaccine against tuberculosis (TB). Subunit boosters are considered a viable strategy to enhance BCG efficacy, which often wanes in adolescence. While many studies on booster subunit vaccines have concentrated on recombinant proteins, here we developed a novel modular peptide-based subunit vaccine platform that is flexible, cold-chain independent and customizable to diverse circumstances and populations. Each individual peptide building block consists of a linear arrangement comprising a 15-leucine self-assembly inducer moiety, a Mycobacterium tuberculosis (Mtb) target epitope and an HLA-E binding moiety, with each moiety separated by a triple lysine spacer. The building blocks, in any combination, were able to form a multiepitope nanoparticle. Six Mtb epitopes were selected to produce the self-assembling and self-adjuvanting peptide-based TB nano-vaccine candidate PNx6. In vivo vaccination-challenge experiments demonstrated that subcutaneous boost of parenteral BCG immunization with PNx6 significantly enhanced its immunogenicity and improved its protective efficacy in a murine model of TB by more than 5-fold. Our study present evidence that purely amphiphilic peptides self-assemble into self-adjuvanting nanoparticles with appropriate size and morphology for TB vaccination with great potential for a multitude of other diseases.

  • Mus musculus (House mouse)
  • Immunology and Microbiology

Alcohol-associated liver disease is accompanied by microbial dysbiosis, increased intestinal permeability and hepatic exposure to translocated microbial products that contribute to disease progression. A key strategy to generate immune protection against invading pathogens is the secretion of IgA in the gut. Intestinal IgA levels depend on the polymeric immunoglobulin receptor (pIgR), which transports IgA across the epithelial barrier into the intestinal lumen and hepatic canaliculi. Here, we aimed to address the function of pIgR during ethanol-induced liver disease.
pIgR and IgA were assessed in livers from patients with alcohol-associated hepatitis and controls. Wild-type and pIgR-deficient (pIgR-/- ) littermates were subjected to the chronic-binge (NIAAA model) and Lieber-DeCarli feeding model for 8 weeks. Hepatic pIgR re-expression was established in pIgR-/- mice using adeno-associated virus serotype 8 (AAV8)-mediated pIgR expression in hepatocytes.
Livers of patients with alcohol-associated hepatitis demonstrated an increased colocalisation of pIgR and IgA within canaliculi and apical poles of hepatocytes. pIgR-deficient mice developed increased liver injury, steatosis and inflammation after ethanol feeding compared with wild-type littermates. Furthermore, mice lacking pIgR demonstrated increased plasma lipopolysaccharide levels and more hepatic bacteria, indicating elevated bacterial translocation. Treatment with non-absorbable antibiotics prevented ethanol-induced liver disease in pIgR-/- mice. Injection of AAV8 expressing pIgR into pIgR-/- mice prior to ethanol feeding increased intestinal IgA levels and ameliorated ethanol-induced steatohepatitis compared with pIgR-/- mice injected with control-AAV8 by reducing bacterial translocation.
Our results highlight that dysfunctional hepatic pIgR enhances alcohol-associated liver disease due to impaired antimicrobial defence by IgA in the gut.
© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.

Laboratory mice with a wild microbiota generate strong allergic immune responses.

In Science Immunology on 29 September 2023 by Ma, J., Urgard, E., et al.

Allergic disorders are caused by a combination of hereditary and environmental factors. The hygiene hypothesis postulates that early-life microbial exposures impede the development of subsequent allergic disease. Recently developed "wildling" mice are genetically identical to standard laboratory specific pathogen-free (SPF) mice but are housed under seminatural conditions and have rich microbial exposures from birth. Thus, by comparing conventional SPF mice with wildlings, we can uncouple the impact of lifelong microbial exposures from genetic factors on the allergic immune response. We found that wildlings developed larger populations of antigen-experienced T cells than conventional SPF mice, which included interleukin-10-producing CD4 T cells specific for commensal Lactobacilli strains and allergy-promoting T helper 2 (TH2) cells. In models of airway exposure to house dust mite (HDM), recombinant interleukin-33, or Alternaria alternata, wildlings developed strong allergic inflammation, characterized by eosinophil recruitment, goblet cell metaplasia, and antigen-specific immunoglobulin G1 (IgG1) and IgE responses. Wildlings developed robust de novo TH2 cell responses to incoming allergens, whereas preexisting TH2 cells could also be recruited into the allergic immune response in a cytokine-driven and TCR-independent fashion. Thus, wildling mice, which experience diverse and lifelong microbial exposures, were not protected from developing pathological allergic immune responses. Instead, wildlings mounted robust allergic responses to incoming allergens, shedding new light on the hygiene hypothesis.

  • Immunology and Microbiology
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