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Despite their efficacy, the currently available polio vaccines, oral polio vaccine (OPV) and inactivated polio vaccine (IPV), possess inherent flaws posing significant challenges in the global eradication of polio. OPV, which uses live Sabin attenuated strains, carries the risk of reversion to pathogenic forms and causing vaccine-associated paralytic poliomyelitis (VAPP) and vaccine-derived polio disease (VDPD) in incompletely vaccinated or immune-compromised individuals. Conventional IPVs, which are non-replicative, are more expensive to manufacture and introduce biohazard and biosecurity risks due to the use of neuropathogenic strains in production. These types of limitations have led to a call by the Global Polio Eradication Initiative and others for the development of updated polio vaccines. We are developing a novel Ultraviolet-C radiation (UVC) inactivation method that preserves immunogenicity and is compatible with attenuated strains of polio. The method incorporates an antioxidant complex, manganese-decapeptide-phosphate (MDP), derived from the radioresistant bacterium Deinococcus radiodurans. The inclusion of MDP protects the immunogenic neutralizing epitopes from damage during UVC inactivation. The novel vaccine candidate, ultraIPV TM , produced using these methods demonstrates three crucial attributes: complete inactivation, which precludes the risk of vaccine-associated disease; use of non-pathogenic strains to reduce production risks; and significantly enhanced yield of doses per milligram of input virus, which could increase vaccine supply while reducing costs. Additionally, ultraIPV TM retains antigenicity post-freeze-thaw cycles, a testament to its robustness., Competing Interests: Competing interests G.J.T., J.K.T., R.V.B., T.J.W., S.J.D., D.A.M., and A.V.K. are employees of Biological Mimetics, Inc., which is the recipient of the NIH grant and DTRA contract that provided the majority of the funding for the project. All other authors have no competing interests., (© 2024. The Author(s).)

Acinetobacter baumannii causes multi-system diseases in both nosocomial settings and a pre-disposed general population. The bacterium is not only desiccation-resistant but also notoriously resistant to multiple antibiotics and drugs of last resort including carbapenem, colistin, and sulbactam. The World Health Organization has categorized carbapenem-resistant A. baumannii at the top of its critical pathogen list in a bid to direct urgent countermeasure development. Several early-stage vaccines have shown a range of efficacies in healthy mice, but no vaccine candidates have advanced into clinical trials. Herein, we report our findings that both an ionizing γ-radiation-inactivated and a non-ionizing ultraviolet C-inactivated whole-cell vaccine candidate protects neutropenic mice from pulmonary challenge with virulent AB5075, a particularly pathogenic isolate. In addition, we demonstrate that a humoral response is sufficient for this protection via the passive immunization of neutropenic mice., Competing Interests: SJD, RVB, JKT, TJW, DAM, NJPERT, and GJT are employees of Biological Mimetics, Inc. The commercial nature of Biological Mimetics, Inc. does not alter the belief in, or the ability to adhere to the policies of the journal regarding data or material sharing or wider ethical standards. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dollery, Zurawski, Bushnell, Tobin, Wiggins, MacLeod, Tasker, Alamneh, Abu-Taleb, Czintos, Su, Escatte, Meeks, Daly and Tobin.)

Acinetobacter baumannii is a bacterial pathogen that is often multidrug-resistant (MDR) and causes a range of life-threatening illnesses, including pneumonia, septicemia, and wound infections. Some antibiotic treatments can reduce mortality if dosed early enough before an infection progresses, but there are few other treatment options when it comes to MDR-infection. Although several prophylactic strategies have been assessed, no vaccine candidates have advanced to clinical trials or have been approved. Herein, we rapidly produced protective whole-cell immunogens from planktonic and biofilm-like cultures of A. baumannii , strain AB5075 grown using a variety of methods. After selecting a panel of five cultures based on distinct protein profiles, replicative activity was extinguished by exposure to 10 kGy gamma radiation in the presence of a Deinococcus antioxidant complex composed of manganous (Mn 2+ ) ions, a decapeptide, and orthophosphate. Mn 2+ antioxidants prevent hydroxylation and carbonylation of irradiated proteins, but do not protect nucleic acids, yielding replication-deficient immunogenic A. baumannii vaccine candidates. Mice were immunized and boosted twice with 1.0 × 10 7 irradiated bacterial cells and then challenged intranasally with AB5075 using two mouse models. Planktonic cultures grown for 16 h in rich media and biofilm cultures grown in static cultures underneath minimal (M9) media stimulated immunity that led to 80-100% protection.

A concerted action on the part of international agencies and national governments has resulted in the near-eradication of poliomyelitis. However, both the oral polio vaccine (OPV) and the inactivated polio vaccine (IPV) have deficiencies which make them suboptimal for use after global eradication. OPV is composed of attenuated Sabin strains and stimulates robust immunity, but may revert to neurovirulent forms in the intestine which can be shed and infect susceptible contacts. The majority of IPV products are manufactured using pathogenic strains inactivated with formalin. Upon eradication, the production of large quantities of pathogenic virus will present an increased biosecurity hazard. A logical ideal endgame vaccine would be an inactivated form of an attenuated strain that could afford protective immunity while safely producing larger numbers of doses per unit of virus stock than current vaccines. We report here the development of an ionizing radiation (IR)-inactivated Sabin-based vaccine using a reconstituted Mn-decapeptide (MDP) antioxidant complex derived from the radioresistant bacterium Deinococcus radiodurans. In bacteria, Mn2+-peptide antioxidants protect proteins from oxidative damage caused by extreme radiation exposure. Here we show for the first time, that MDP can protect immunogenic neutralizing epitopes in picornaviruses. MDP protects epitopes in Polio Virus 1 and 2 Sabin strains (PV1-S and PV2-S, respectively), but viral genomic RNA is not protected during supralethal irradiation. IR-inactivated Sabin viruses stimulated equivalent or improved neutralizing antibody responses in Wistar rats compared to the commercially used IPV products. Our approach reduces the biosecurity risk of the current PV vaccine production method by utilizing the Sabin strains instead of the wild type neurovirulent strains. Additionally, the IR-inactivation approach could provide a simpler, faster and less costly process for producing a more immunogenic IPV. Gamma-irradiation is a well-known method of virus inactivation and this vaccine approach could be adapted to any pathogen of interest., Competing Interests: Two co-authors are employed by the Department of Defense. MJD is a Professor at the Uniformed Services University Health Sciences. Dr. Daly participated in all aspects of the project but he and his University have no control over funding. HNM is a Program Officer at one of the two funding agencies, DTRA. Dr. Meeks played a role in the conceptualization of the overarching research aims, in the analysis and interpretation of the data, and in manuscript editing. Dr. Meeks has no role in decisions regarding funding these types of applications that are submitted to DTRA. The two funding agencies provided support in the form of salaries for all authors with the exception of MJD who is a fully-funded Professor at USUHS and HNM who is a fully-funded employee at DTRA. The specific roles of these authors are articulated in the ‘author contributions’ section. The commercial nature of Biological Mimetics, Inc. does not alter our adherence to PLOS ONE policies on sharing data and materials.

Tick-borne encephalitis virus (TBEV) is an emerging pathogen in Europe and Asia. We investigated TBEV in Kyrgyzstan by collecting small mammals and ticks from diverse localities and analyzing them for evidence of TBEV infection. We found TBEV circulating in Kyrgyzstan much farther south and at higher altitudes than previously reported.

We sampled vole populations in Ukraine with the dual goal of characterizing population diversity and of providing a biogeographic perspective to evaluate experimental designs used for previous studies. Our data indicate that genetic diversity in bank vole populations is widely variable across regions and that diversity estimates in contaminated sites are unremarkable compared to those in uncontaminated areas. Furthermore, the relative frequencies of haplotypes have remained statistically identical throughout multiple sampling periods. Thus, the genetic data from bank vole populations in Ukraine fail to support the hypothesis that mutational changes in contaminated regions are the product of exposure to Chernobyl radiation. Our results suggest that genetic diversity in radioactive regions of Ukraine is probably a function of natural geographic variation rather than increased mutational pressure from radiation exposure and underscore the importance of adequate geographic sampling in studies designed to elucidate the effects of toxicant exposure.

Three previous studies at Chernobyl, Ukraine, documented elevated mitochondrial DNA diversity in bank voles (Clethrionomys glareolus) from radioactively contaminated sites. Little evidence was found to link patterns of diversity in contaminated areas to radiation exposure, but the experimental design precluded discriminating among alternative explanations for elevated diversity in exposed groups. Reference sites selected for the studies were relatively distant from contaminated sites and, additionally, were separated from contaminated sites by large river systems; thus, we hypothesized that differences among sites were correlated with geographic isolation rather than with radiation exposure. For the present study, we added three reference sites, which were selected based on minimal radioactive contamination, proximity to contaminated sites, and absence of obvious barriers to dispersal. We hypothesized that neighboring reference sites should exhibit levels and patterns of diversity similar to those of contaminated sites if the previously detected differences were, in fact, caused by geographic isolation. Indeed, levels of diversity in nearby reference sites are comparable to levels in contaminated sites. Additionally, nearby reference sites contain several haplotypes not observed at other study sites. Our results suggest that levels of diversity in contaminated regions are more plausibly explained by ecological and historical factors than by increased mutational pressure resulting from exposure to Chernobyl radiation.