Biology subjects

Pedersen, G. K.

Publications and source records attributed to Pedersen, G. K..

4 recordsLinked to original sources

bioRxiv2023

Tailoring Tfh Profiles Enhances Antibody Persistence to a Clade C HIV-1 Vaccine in Rhesus Macaques

CD4 T follicular helper cells (Tfh) are essential for establishing serological memory and have distinct helper attributes that impact both the quantity and quality of the antibody response. Insights into Tfh subsets that promote antibody persistence and functional capacity can critically inform vaccine design. Based on the Tfh profiles evoked by the live attenuated measles virus vaccine, renowned for its ability to establish durable humoral immunity, we investigated the potential of a Tfh1/17 recall response during the boost phase to enhance persistence of HIV-1 Envelope (Env) antibodies in rhesus macaques. Using a DNA-prime encoding gp160 antigen and Tfh polarizing cytokines (interferon protein-10 (IP-10) and interleukin-6 (IL-6)), followed by a gp140 protein boost formulated in a cationic liposome-based adjuvant (CAF01), we successfully generated germinal center (GC) Tfh1/17 cells. In contrast, a similar DNA-prime (including IP-10) followed by gp140 formulated with monophosphoryl lipid A (MPLA)+QS-21 adjuvant predominantly induced GC Tfh1 cells. While the generation of GC Tfh1/17 cells with CAF01 and GC Tfh1 cells with MPLA+QS-21 induced comparable peak Env antibodies, the latter group demonstrated significantly greater antibody concentrations at week 8 after final immunization which persisted up to 30 weeks (gp140 IgG ng/ml-MPLA; 5500; CAF01, 2155; p <0.05). Notably, interferon {gamma}+ Env-specific Tfh responses were consistently higher with gp140 in MPLA+QS-21 and positively correlated with Env antibody persistence. These findings suggest that vaccine platforms maximizing GC Tfh1 induction promote persistent Env antibodies, important for protective immunity against HIV.

immunology↗

bioRxiv2023

Effects of different immunomodulating liposome-based adjuvants and injection sites on immunogenicity in pigs

Vaccine adjuvants are able to boost immune responses and steer immunity towards a desired direction. Liposome-based cationic adjuvant formulations (CAFs) are effective in inducing cell-mediated immune responses in mice, non-human primates and humans. In the translation from mouse to humans, pigs could play an important role. In this study, we thus used commercial pigs housed under field conditions to investigate the effects of four different CAFs incorporating distinct immunomodulators: C-type lectin receptor ligands trehalose-6,6-dibehenate and monomycolyl glycerol, toll-like receptor ligand Poly(I:C) or retinoic acid. The vaccines were formulated with a recombinant Chlamydia model protein antigen and administered via distinct injection routes. All adjuvants significantly increased antigen-specific IgA and IgG in serum, compared to non-adjuvanted antigen. Administering the vaccines through intramuscular and intraperitoneal routes induced significantly higher antigen-specific IgA and IgG serum antibodies, than the perirectal route. Although the immunizations triggered cell-mediated immunity, no significant differences between the adjuvants or injection sites were detected by intracellular flow cytometry or cytokine-release assays. Genes depicting T cell subtypes were monitored by qPCR, which revealed minor differences only. Our findings suggest that the adjuvant-specific signature of the tested adjuvant immunomodulation does not translate well from mice to pigs. This study provides new insights into immune responses to CAFs in the pig model, and highlights that adjuvant studies should be ideally carried out in the intended species of interest.

immunology↗

bioRxiv2023

A novel adjuvant formulation induces robust Th1/Th17 memory and mucosal recall responses in Non-Human Primates

After clean drinking water, vaccination is the most impactful global health intervention. However, development of new vaccines against difficult-to-target diseases is hampered by the lack of diverse adjuvants for human use. Of particular interest, none of the currently available adjuvants induce Th17 cells. Here, we develop and test an improved liposomal adjuvant, termed CAF(R)10b, that incorporates a TLR-9 agonist. In a head-to-head study in non-human primates (NHPs), immunization with antigen adjuvanted with CAF(R)10b induced significantly increased antibody and cellular immune responses compared to previous CAF(R) adjuvants, already in clinical trials. This was not seen in the mouse model, demonstrating that adjuvant effects can be highly species specific. Importantly, intramuscular immunization of NHPs with CAF(R)10b induced robust Th17 responses that were observed in circulation half a year after vaccination. Furthermore, subsequent instillation of unadjuvanted antigen into the skin and lungs of these memory animals led to significant recall responses including transient local lung inflammation observed by Positron Emission Tomography-Computed Tomography (PET-CT), elevated antibody titers, and expanded systemic and local Th1 and Th17 responses, including >20% antigen-specific T cells in the bronchoalveolar lavage. Overall, CAF(R)10b demonstrated an adjuvant able to drive true memory antibody, Th1 and Th17 vaccine-responses across rodent and primate species, supporting its translational potential.

immunology↗

bioRxiv2021

A novel Pan-viral prophylaxis strategy using vaccine adjuvant CAF09b protects against influenza virus infection

The SARS-CoV-2 pandemic caused a massive health and societal crisis, although the fast development of effective vaccines reduced some of the impact. To prepare for future pandemics, a pan-viral prophylaxis could be used to control the initial virus outbreak in the period prior to vaccine approval. The liposomal vaccine adjuvant CAF(R)09b contains the TLR3 agonist polyinosinic:polycytidylic acid, which induces a type I interferon (IFN-I) response and an antiviral state in the affected tissues. When testing CAF09b as a potential pan-viral prophylaxis, we observed that intranasal administration of CAF09b to mice resulted in an influx of innate immune cells into the nose and lungs and upregulation of IFN-I related gene expression. When CAF09b was administered prior to challenge with mouse-adapted influenza A/Puerto Rico/8/1934 virus, it protected from severe disease, although virus was still detectable in the lungs. However, when CAF09b was administered after influenza challenge, the mice had a similar disease course to controls. In conclusion, CAF09b may be a suitable candidate as a pan-viral prophylactic treatment for epidemic viruses, but must be administered prior to virus exposure to be effective.

immunology↗