Seasonal dynamics of Haemaphysalis tick species as SFTSV vectors in South Korea.

Ticks pose a significant public health threat due to their ability to transmit various pathogens, including emerging tick-borne diseases. This study conducted a comprehensive surveillance of Haemaphysalis tick species and their severe fever with thrombocytopenia syndrome virus (SFTSV) infection rates in South Korea throughout the year 2023, from January to December. To ensure accurate and rapid identification of the prevalent Haemaphysalis tick species in South Korea, we designed PCR primer sets targeting the ITS1 gene, specifically distinguishing Haemaphysalis longicornis from Haemaphysalis flava. Among the 10,343 ticks collected from wild animals, H. longicornis constituted the majority, accounting for 65.5% (6,784/10,343 ticks), followed by H. flava at 33.8% (3,491/10,343 ticks), and Ixodes nipponensis at 0.7% (68/10,343 ticks). These identified ticks were then categorized into 811 pools, with 63 pools testing positive for SFTSV. Remarkably, the prevalence of SFTSV-positive H. longicornis ticks peaked during the summer months, aligning with heightened human outdoor activities and, consequently, an increased risk of human exposure. Conversely, it is noteworthy that H. flava exhibited a higher prevalence during the winter season, reaching its peak in January, with an SFTSV minimum infection rate similar to that of H. longicornis. These findings underscore the year-round presence of Haemaphysalis ticks as potential vectors for SFTSV, extending the temporal window for potential human exposure. Consequently, these results emphasize the necessity for active and continuous field surveillance to comprehensively understand and mitigate the public health risks associated with these tick-borne pathogens. IMPORTANCE: To date, the majority of tick surveillance studies have primarily focused on warmer seasons, which are considered optimal periods for ticks to actively seek hosts and transmit pathogens through blood-feeding activities. Consequently, tick species active during winter have often been overlooked, leading to an underestimation of their significance in transmitting severe fever with thrombocytopenia syndrome virus (SFTSV). In this study, we aimed to examine year-round tick prevalence with SFTSV and illuminate the role of the winter-dominant species, Haemaphysalis flava, in South Korea. Through rigorous identification facilitated by a primer set designed specifically for this purpose, we emphasize that H. flava, a competent vector species, harbors SFTSV in the winter season, thereby acting as an overwintering reservoir for the virus. This phenomenon may contribute to a higher infection rate among ticks in the following year.

Enhancing Omicron Sublineage Neutralization: Insights From Bivalent and Monovalent COVID-19 Booster Vaccines and Recent SARS-CoV-2 Omicron Variant Infections.

BACKGROUND: Omicron variants have rapidly diversified into sublineages with mutations that enhance immune evasion, posing challenges for vaccination and antibody responses. This study aimed to compare serum cross-neutralizing antibody responses against various SARS-CoV-2 Omicron sublineages (BA.1, BA.5, XBB.1.17.1, FK.1.1, and JN.1) in recipients of monovalent COVID-19 boosters, bivalent booster recipients, and individuals who had recovered from Omicron BA.5 infections. METHODS: We conducted a micro-neutralization assay on serum samples from monovalent BNT162b2 booster recipients (N = 54), bivalent BNT162b2 booster recipients (N = 24), and SARS-CoV-2 Omicron BA.5-recovered individuals (N = 13). The history of SARS-CoV-2 Omicron infection was assessed using ELISA against the SARS-CoV-2 NP protein. RESULTS: Bivalent booster recipients exhibited significantly enhanced neutralization efficacy against Omicron sublineages compared to those who had received monovalent booster vaccinations. Omicron BA.5-recovered individuals displayed similar neutralizing antibodies (NAbs) to the bivalent booster recipients. Despite the improved neutralization in bivalent recipients and BA.5-recovered individuals, there were limitations in neutralization against the recently emerged Omicron subvariants: XBB.1.17.1 FK.1.1, and JN.1. In both monovalent and bivalent booster recipients, a history of Omicron breakthrough infection was associated with relatively higher geometric mean titers of NAbs against Omicron BA.1, BA.5, and XBB.1.17.1 variants. CONCLUSION: This study underscores the intricate interplay between vaccination strategies, immune imprinting, and the dynamic landscape of SARS-CoV-2 variants. Although bivalent boosters enhance neutralization, addressing the challenge of emerging sublineages like XBB.1.17.1, FK.1.1, and JN.1 may necessitate the development of tailored vaccines, underscoring the need for ongoing adaptation to effectively combat this highly mutable virus.

SARS-CoV-2 variants with NSP12 P323L/G671S mutations display enhanced virus replication in ferret upper airways and higher transmissibility.

With the emergence of multiple predominant SARS-CoV-2 variants, it becomes important to have a comprehensive assessment of their viral fitness and transmissibility. Here, we demonstrate that natural temperature differences between the upper (33°C) and lower (37°C) respiratory tract have profound effects on SARS-CoV-2 replication and transmissibility. Specifically, SARS-CoV-2 variants containing the NSP12 mutations P323L or P323L/G671S exhibit enhanced RNA-dependent RNA polymerase (RdRp) activity at 33°C compared with 37°C and high transmissibility. Molecular dynamics simulations and microscale thermophoresis demonstrate that the NSP12 P323L and P323L/G671S mutations stabilize the NSP12-NSP7-NSP8 complex through hydrophobic effects, leading to increased viral RdRp activity. Furthermore, competitive transmissibility assay reveals that reverse genetic (RG)-P323L or RG-P323L/G671S NSP12 outcompetes RG-WT (wild-type) NSP12 for replication in the upper respiratory tract, allowing markedly rapid transmissibility. This suggests that NSP12 P323L or P323L/G671S mutation of SARS-CoV-2 is associated with increased RdRp complex stability and enzymatic activity, promoting efficient transmissibility.

SARS-CoV-2 variants show temperature-dependent enhanced polymerase activity in the upper respiratory tract and high transmissibility.

With the convergent global emergence of SARS-CoV-2 variants of concern (VOC), a precise comparison study of viral fitness and transmission characteristics is necessary for the prediction of dominant VOCs and the development of suitable countermeasures. While airway temperature plays important roles in the fitness and transmissibility of respiratory tract viruses, it has not been well studied with SARS-CoV-2. Here we demonstrate that natural temperature differences between the upper (33°C) and lower (37°C) respiratory tract have profound effects on SARS-CoV-2 replication and transmission. Specifically, SARS-COV-2 variants containing the P323L or P323L/G671S mutation in the NSP12 RNA-dependent RNA polymerase (RdRp) exhibited enhanced RdRp enzymatic activity at 33°C compared to 37°C and high transmissibility in ferrets. MicroScale Thermophoresis demonstrated that the NSP12 P323L or P323L/G671S mutation stabilized the NSP12-NSP7-NSP8 complex interaction. Furthermore, reverse genetics-derived SARS-CoV-2 variants containing the NSP12 P323L or P323L/G671S mutation displayed enhanced replication at 33°C, and high transmission in ferrets. This suggests that the evolutionarily forced NSP12 P323L and P323L/G671S mutations of recent SARS-CoV-2 VOC strains are associated with increases of the RdRp complex stability and enzymatic activity, promoting the high transmissibility.

Enhanced antibody responses in fully vaccinated individuals against pan-SARS-CoV-2 variants following Omicron breakthrough infection.

Omicron has become the globally dominant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, creating additional challenges due to its ability to evade neutralization. Here, we report that neutralizing antibodies against Omicron variants are undetected following COVID-19 infection with ancestral or past SARS-CoV-2 variant viruses or after two-dose mRNA vaccination. Compared with two-dose vaccination, a three-dose vaccination course induces broad neutralizing antibody responses with improved durability against different SARS-CoV-2 variants, although neutralizing antibody titers against Omicron remain low. Intriguingly, among individuals with three-dose vaccination, Omicron breakthrough infection substantially augments serum neutralizing activity against a broad spectrum of SARS-CoV-2 variants, including Omicron variants BA.1, BA.2, and BA.5. Additionally, after Omicron breakthrough infection, memory T cells respond to the spike proteins of both ancestral and Omicron SARS-CoV-2 by producing cytokines with polyfunctionality. These results suggest that Omicron breakthrough infection following three-dose mRNA vaccination induces pan-SARS-CoV-2 immunity that may protect against emerging SARS-CoV-2 variants of concern.