The authors thank Terence Dermody at the University of Pittsburgh, Pittsburgh, PA, for providing the CHIKV181/25 infectious clone

The authors thank Terence Dermody at the University of Pittsburgh, Pittsburgh, PA, for providing the CHIKV181/25 infectious clone. that IXCHIQ efficiently and potently elicits cross-nAb breadth that extends to related alphaviruses in a manner similar to natural CHIKV infection, which may have important implications for individuals that are susceptible to alphavirus co-circulation in regions of potential vaccine rollout. Keywords: chikungunya virus (CHIKV), alphaviruses, IXCHIQ, vaccine, cross-neutralization, antibody, breadth, infection 1. Introduction Chikungunya virus (CHIKV) is a Rabbit polyclonal to Amyloid beta A4.APP a cell surface receptor that influences neurite growth, neuronal adhesion and axonogenesis.Cleaved by secretases to form a number of peptides, some of which bind to the acetyltransferase complex Fe65/TIP60 to promote transcriptional activation.The A human pathogenic alphavirus responsible for sporadic epidemics that have burdened 100+ countries over 50 years. From 2013 to 2023, there were over 3.68 million suspected and confirmed cases in 50 countries in the Americas [1]. Alphaviruses are part of the family composing a number of additional emerging human pathogenic viruses that are predominantly mosquito-transmitted. CHIKV belongs to the Semliki Forest antigenic complex, which includes seven additional viruses with varying degrees of cross-reactivity due to shared antigenicity. While there are three distinct lineages of CHIKV, Asian lineage, East Central South African (ECSA) lineage, and West African lineage, a fourth Indian Ocean lineage (IOL) has been proposed to exist. Immunologically, these lineages conform to a single serotype [2,3]. It has been observed that even decades after large CHIKV outbreaks, herd immunity limits additional outbreaks or the emergence of new CHIKV strains in that region, further supporting a single serotype [3]. Predominantly circulating CHIKV strains have yet to accumulate mutations to confer host antibody-neutralization escape, but the viral evolution of CHIKV continues to be cause for concern after single mutations have conferred transmissibility in new mosquito vectors [4]. This warrants investigation to identify differences in CHIKV antibody potency against diverse strains. Notable emerging viruses that have contributed to sporadic outbreaks within the Semliki Forest antigenic GDC-0834 Racemate complex include Onyong-nyong virus (ONNV), Mayaro virus (MAYV), and Ross River virus (RRV). Each of these viruses has been shown to co-circulate with CHIKV [5,6,7], and they are transmitted by similar vectors as several flaviviruses such as dengue and Zika viruses [8]. This leads to co-circulation of diverse human pathogenic arbovirus infections, presenting urgent public health concern. Vaccines to counter CHIKV have been in development for decades based on virus-like particle, viral vector, live-attenuated virus, nucleic acid, subunit, and inactivated viral vaccine platforms. The primary goal of these vaccine platforms has been to elicit high levels GDC-0834 Racemate of neutralizing GDC-0834 Racemate antibodies, which are generally accepted as the main correlate of protection, although protective roles of T cells have also been established [9,10]. There are several CHIKV vaccines currently in clinical trials, with two vaccines in Phase I, two vaccines in Phase II, and two vaccines in Phase III trials [11]. In November of 2023, the U.S. Food and Drug Administration (FDA) approved the CHIKV vaccine IXCHIQ (VLA1553), which was a huge step for the alphavirus field, especially amidst a year with over 500,000 CHIKV cases, with the epicenter in Brazil, where many additional arboviruses burden the community. The European Medicines Agency has also now officially approved marketing authorization of IXCHIQ in the European Union [12]. Under the OPEN regulatory procedure, this review was joined by other regulators including Brazilian ANVISA, marking the first endemic country reviews [13]. The IXCHIQ vaccine is a single-dose, live-attenuated vaccine (LAV) platform based upon the CHIKVLR2006-OPY1 backbone containing a large genetic deletion in nsP3 [14]. IXCHIQ was tested in mice and cynomolgus macaques to establish a protective antibody threshold due to the challenges of conducting an efficacy trial given the sporadic nature of CHIKV outbreaks [14,15,16,17]. IXCHIQ has now been tested in over 4000 individuals in non-endemic settings and is generally immunogenic and well tolerated, although viremia and some side effects including headache, fever, arthralgia, and myalgia have been GDC-0834 Racemate noted [18,19,20]. Additional trials are.