is definitely a paid advisor to Novartis, Akouos, Affinia Therapeutics and serves within the Table of Directors of Affinia, Addgene and Odylia Therapeutics. main response maximum antibody levels were reached. The boost elicited an increase in antibodies against several Omicron variants, but no increase was recognized in the antibody titers for additional variants. The anti-vector reactions were low and showed some improved subsequent boosts but generally declined over time. The potent perfect vaccination limited the detection of the improving effect, and therefore, the effect of anti-vector immunity was not fully elucidated. These data display that PARVAX can be efficiently re-administered and induce a novel antigenic response. Keywords: PARVAX platform, genetic vaccine, re-administration, boost, SARS-CoV-2, antibody breadth, anti-vector response 1. Intro The public health emergency caused by COVID-19 induced an unprecedented volume of research to test various vaccine platforms against the disease (https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines (accessed on 1 February 2024)) [1,2,3,4]. Among these, we developed the PARVAX platform, a genetic vaccine based on adeno-associated disease (AAV) [5,6]. This platform uses a specific AAV serogroup of capsids, which includes rh32.33 and AAV11, with minimal organic pre-existing immunity in human beings [6,7]. Importantly, unlike additional vectors in the AAV class, these serotypes show a tropism for antigen-presenting cells (APCs) and activate the toll-like receptor (TLR) 9 pathway, therefore effectuating a cytotoxic T-cell response toward the encoded transgene antigen Voruciclib hydrochloride that results in the removal of transduced cells, therefore limiting vector persistence and manifestation [8,9,10]. PARVAX candidates for SARS-CoV-2 demonstrate durable, up to 2-12 months neutralizing antibody responses, which provide near-sterilizing upper and lower airway protection in cynomolgus macaques after a single-dose administration. Voruciclib hydrochloride These qualities combined with established commercial and low-cost developing processes and room heat stability make this platform Rabbit Polyclonal to RIN3 imminently feasible, scalable, and affordable for vaccine applications [6]. Viral vector-based vaccines, such as adenovirus Voruciclib hydrochloride vaccines, are genetic vaccines that consist of a genetically designed computer virus that carries the gene of the antigen of interest. Upon the administration of the vaccine, the antigen is usually expressed in resident cells, and the transduction of the viral vector functions as adjuvant to the vaccination [8,9,10]. Some of these viral vector platforms have demonstrated the potential to induce potent humoral and cellular responses against the antigen, even following a single dose in certain cases [11,12]. However, some viral vectors are based on viruses that circulate in human populations, and consequently, their utility may be limited in individuals who have anti-vector antibodies due to a prior natural infection [13]. While many AAVs have significant pre-existing immunity in humans, PARVAXs AAV technology is usually minimally seroprevalent [7]. Regardless of the anti-vector immunity level caused by natural contamination, any administration in the context of a vaccine or gene therapy application with a serologically cross-reactive viral vector may hamper future administrations of the same modality [14]. In the context of PARVAX, prior data indicate minimal to no cross-reactivity of the particular AAV serotype used Voruciclib hydrochloride with commonly used gene therapy vectors in nonhuman primate studies (as well as Voruciclib hydrochloride in previous studies in rabbits) [7]. Here, we sought to assess whether the PARVAX platform can provide a boost following a second administration in mouse and nonhuman primate models. While PARVAX was shown to lead to sustained antibody responses from a single-dose administration, a second administration may be desired to match breadth or lengthen the period of the primary response (e.g., to address VOCs in COVID-19) or as a vaccine for another class of immunogens (e.g., influenza following COVID-19). 2. Material and Methods 2.1. Vaccine Candidates AC3 is an adeno-associated computer virus serotype rh32.33 (AAVrh32.33)-based candidate.