Live Vaccine Research Articles

Current status of recombinant duck enteritis virus vector vaccine research

Duck enteritis virus (DEV), the pathogen of duck viral enteritis, belongs to the α-herpesvirus subfamily. Like other herpesviruses, it has a large genome with multiple non-coding and non-essential regions for viral replication. It is suitable as a live virus vector for inserting and expressing antigenic genes from other pathogens to develop multivalent vaccines. With the advancement of molecular biology research and experimental technology, genetic modification of the DEV genome has matured, leading to the successful construction of recombinant DEV live vector vaccines. These vaccines have demonstrated the ability to resist DEV and other pathogens, showing potential as recombinant viral vaccine vectors and playing a crucial role in the development of new avian vaccines. This article provides an overview of the progress of research on recombinant vaccines using DEV as the vector. It includes the biological characteristics of DEV and its advantages and limitations as a vaccine vector, methods for constructing recombinant DEV, the technical platform for efficiently building recombinant DEV, factors affecting the immune protection efficacy of recombinant DEV, and the application of recombinant DEV in vaccine development. Aiming to provide a reference for the development of duck enteritis virus vector-based vaccines.

Field Investigation Evaluating the Efficacy of Porcine Reproductive and Respiratory Syndrome Virus Type 2 (PRRSV-2) Modified Live Vaccines in Nursery Pigs Exposed to Multiple Heterologous PRRSV Strains

This study was conducted to evaluate the protective efficacy of modified live vaccines (MLVs) against porcine reproductive and respiratory syndrome (PRRS) in nursery pigs in a worst case scenario where MLV does not match the genetic profile of the field isolate, different MLVs are used for sows and piglets, and piglets are naturally exposed to genetically distinct heterologous PRRS virus (PRRSV) isolates. We divided 76,075, 2-week-old piglets from a seropositive sow herd vaccinated with US1-MLV into four groups. US1-MLV, US2-MLV, and US3-MLV groups were vaccinated with PRRSV-2 MLV including Ingelvac® PRRS MLV (Boehringer Ingelheim, Ingelheim am Rhein, Germany), HP-PRRSV-2 based MLV (Harbin Veterinary Research Institute, CAAS, Harbin, China), and Prime Pac® PRRS (MSD Animal Health, Rahway, NJ, USA), respectively. The NonVac group was left unvaccinated. At 0, 14, 28, and 56 days post-vaccination (DPV), sera were assayed for the presence of PRRSV-specific antibodies using ELISA and serum neutralization (SN), and PRRSV RNA using PCR. Average daily gain (ADG) and survival rates were compared between treatment groups. The results demonstrated vaccinated groups significantly improved in ADG compared to the non-vaccinated control group. Only US1-MLV and US3-MLV were able to significantly reduce mortality associated with field PRRSV infection in nursery pigs. Pigs vaccinated with US3-MLV displayed significantly lower mortality and higher ADG compared to all other groups. Field isolates were isolated and genetically compared to all three MLV vaccines at the start of the trial. The MLV with closest genetic similarity to the field isolate was US2-MLV by ORF5 gene comparison. This provided the lowest protection judging by ADG improvement and mortality reduction, as compared to US1-MLV and US3-MLV. Separately, strains of Thai PRRSV-2 isolates collected in 2017, 2019, and 2020 in the study area were investigated for evolutionary changes. Over time, we observed a shift in PRRSV-2 isolates from lineage 8.7 to lineage 1. The field isolates found shared 82.59–84.42%, 83.75–85.74%, and 84.25–85.90% nucleotide identity with the US1-MLV, US3-MLV and US2-MLV based vaccine, respectively. Our findings suggest genetic similarity between field viruses and vaccine strains should not be used as a predictor of field performance. We found that zootechnical performance of piglets was best in US3-MLV, despite sows being treated with a different vaccine The results also support that different MLVs can be used at different stages of production. Finally, we concluded that the shift from lineage 8.7 to lineage 1 was due to shifts in the worldwide prevalence of PRRSV isolates during that period of time and not due to vaccine recombination between isolates. Overall, MLV vaccine selection should be based on production performance and safety profile.

Evaluation of mucosal adjuvants to chitosan-nanoparticle-based oral subunit vaccine for controlling salmonellosis in broilers

Salmonellosis, a gastrointestinal disease, continues to be one of the major public health concerns worldwide. Poultry meat and eggs are recognized as the major source of Salmonella food poisoning in humans. Our study evaluated the protective efficacy of mannose-conjugated chitosan-nanoparticle (mChitosan-NP)-based subunit vaccine, consisting of immunogenic outer membrane proteins and flagella of Salmonella Enteritidis [mChitosan (OMP+FLA)/FLA-NP], coadministered orally with potent mucosal adjuvants to reduce the colonization of S. Enteritidis in the intestines of broiler chickens. We evaluated the adjuvant effects of three different doses of two well-known mucosal adjuvants, c-di-GMP (stimulator of interferon gene agonist) and whole cell lysate (WCL) of Mycobacterium smegmatis, to improve the efficacy of mChitosan (OMP+FLA)/FLA-NP vaccine. Our data reaffirmed the potent adjuvanticity of both of these adjuvants and identified their optimal dose when entrapped in mChitosan-NP to potentiate the immunogenicity and efficacy of orally delivered mChitosan (OMP+FLA)/FLA-NP vaccine. The physical characteristics of mChitosan (OMP+FLA)/FLA-NP, mChitosan-GMP/FLA-NP, and mChitosan-WCL/FLA-NP formulations revealed a high positive charge (Zeta potential +20–25 mV), size 235–260 nm, and polydispersity index 0.35–0.52, which are conducive for oral delivery. The efficacy in chickens that received oral administration with a combination of the vaccine-adjuvant formulations was evaluated by challenging with Salmonella Enteritidis. Our data showed that mChitosan (OMP+FLA)/FLA-NP WCL at 10 µg/dose formulation consistently reduced the S. Enteritidis load by over 0.5 log10 comparable to a commercial live vaccine at post-challenge days 4 and 10. Immunologically, we observed enhanced systemic and mucosal antibody and cellular (B cells and T-helper cells) immune responses as well as upregulation of expression of immune cytokine genes IFN-γ, TGF-β, and IL-17 in the cecal tonsils of adjuvanted mChitosan-NP Salmonella-subunit-vaccinated birds. Overall, particularly the mucosal adjuvant WCL consistently enhanced the efficacy of mChitosan (OMP+FLA)/FLA-NP vaccine by inducing effective immune responses.

First clinical experiences with the tetravalent live vaccine against dengue (Qdenga ®) in travellers: a multicentric TravelMedVac study in Germany.

A study was conducted to assess the safety and tolerability of the tetravalent live-attenuated dengue vaccine Qdenga®, which received marketing approval in Germany in 2022. The study evaluated vaccine-related reactions in a predominantly dengue-naïve population, highlighting the importance of post-marketing surveillance as an essential component of safety evaluation for newly licensed vaccines. Following dengue vaccination, participants were recruited for an anonymous online questionnaire through the national 'Trav VacNet' network in Germany. The questionnaire focused on post-vaccination reactions up to 18days after the first and second vaccination, as well as previous travel history and coadministration. The study included 1176 participants, with a median age of 39years (IQR 28-56), 53.2% female (n = 625), 46.5% male (n = 547), and 0.3% non-binary participants (n = 4). After the first dose, 51% of the participants reported systemic reactions such as headache (40% (190/474)), weakness (40% (189/474)) and malaise (32% (154/474)), which were most pronounced between days 7-11 post vaccination. After the second dose, localized signs and symptoms such as pain at the injection site (22% (n = 55/250)) were more common. Fever was more common after the first dose (20% (96/474)) vs. 2% (6/250) after the second. Females reported significantly more reactions than males after both vaccinations (1st dose p = 0.0002; 2nd dose p = 0.0003). A total of 334 (28%) co-administrations were reported whereby AEs were reported in 47% (157/333) of participants, with the highest prevalence observed when combined with the Japanese encephalitis vaccine (56.8%, (42/74)). Differences in age groups were observed, with a decrease in reactions in the elderly (≥65years). Vaccine-related reactions were frequently reported, predominantly after the first dose in dengue-naïve participants. Coadministration was a common strategy without significantly increasing side effects. The study provides important insights into reactogenicity and may help improve vaccination strategies in dengue-naïve populations.

Safety and immunogenicity of different 17DD yellow fever vaccines in golden-headed tamarins (Leontopithecus chrysomelas): Inhibition of viremia and RNAemia after homologous live-attenuated vaccination.

Yellow fever (YF) is a viral disease that affects both humans and non-human primates (NHPs). Neotropical monkeys are more severely stricken by YF and the impact of the disease can be devastating to the endangered golden-headed lion tamarins (GHLTs, Leontopithecus chrysomelas). Susceptible GHLTs were immunized with the commercial Brazilian YF 17DD live attenuated vaccine or two other experimental non-replicating YF vaccines: a purified whole-virus, b-propiolactone-inactivated vaccine and a plant-derived recombinant subunit vaccine. Safety, immunogenicity and viremia and RNAemia blockade were characterized. No YF clinical manifestations were observed in any of the GHLTs that received the attenuated virus, either as a vaccine or as the homologous vaccination with the live attenuated vaccine used as the challenge virus. All three concentrations of the attenuated vaccine induced neutralizing antibodies and only one in 16 animals had detectable viremia and RNAemia after challenge. The inactivated vaccine elicited neutralizing antibodies preventing post-challenge viremia and RNAemia in five out of six animals. The plant-based vaccine induced neutralizing antibodies in five out of six animals and prevented viremia and RNAemia in three out of six against challenge. The safety profile and the immunogenicity of the YF attenuated vaccine were demonstrated in GHLTs with a blocking effectiveness over 90%, where blockade can be defined as the capacity to prevent viremia and RNAemia after homologous vaccination with the live attenuated vaccine. The use of the inactivated vaccine in this species served as a preliminary pre-clinical study for this approach and after administration in three-dose regimen demonstrated a blocking profile of 83%. Using a two-dose regimen, the plant-based vaccine was able to block viremia and RNAemia in 50% of the animals. The present study can endorse the use of attenuated or non-replicating yellow fever vaccines in New World primates threatened by the recent disease outbreaks in Brazil.

A simplified vaccination program elicits an immune response comparable to a complex standard vaccination program in commercial layers under field conditions.

Newcastle disease (ND) is a notifiable avian disease responsible for several panzootics, which has resulted in the establishment of mandatory vaccination programs against the virus in several countries including Denmark. This study compared the immune response elicited in layers by the standard vaccination program for ND of a Danish commercial egg production facility with a simplified version of the vaccination program. A commercial flock of layers was followed for 77 weeks from hatching to culling. The flock was divided into two groups according to vaccination program and housed separately. One group received the standard vaccination program consisting of a vector vaccine, a live vaccine (administered twice) and an inactivated vaccine (standard vaccination program). The other group received a newly marketed vector vaccine and the inactivated vaccine of the standard vaccination program (simplified vaccination program). Blood samples were collected at regular intervals from 30 randomly selected layers in each group until culling (77 weeks of age) and analysed for ND antibodies by ELISA assays, which measured antibodies against the nucleoprotein or fusion protein, and hemagglutination inhibition tests. Both vaccination programs provided lasting antibodies until 77 weeks. The simplified vaccination program showed significantly higher fusion protein antibodies and a markedly earlier onset of immunity at five weeks of age (97-100 % seroprevalence) than the standard program. The standard vaccination program reached the same seroprevalence at 14 and 24 weeks of age based on fusion protein antibodies and HI titres, respectively. The inactivated vaccine elicited a boost in antibody titres in both groups, however, boosting with the live vaccine used in the standard vaccination program did not result in an increased antibody response. This might indicate that administering of a vector vaccine prior to a live vaccine inhibits the serological response to the live vaccine.

Examining homology between MPXV and immunogenic VACV-derived peptides.

The mpox virus (MPXV) came to global attention with the 2022 global outbreak. Current vaccination and post-exposure prophylaxis against MPXV consists of live vaccinia whole virus-based vaccines including ACAM2000®, JYNNEOS™, and LC16m8 originally developed against smallpox. Here, we analyzed 152 vaccinia-derived peptides we identified by mass spectrometry for homology with MPXV-1 and MPXV-2 sequences to evaluate their potential relevance to MPXV-specific immunity. We found that 93 (61.2%) of these sequences were 100% homologous to both clades. This supports the long-standing hypothesis that immunologic cross-reactivity is due to sequence homology between poxviruses. Our results also suggest the utility of VACV-derived peptides for an mpox peptide-based vaccine candidate. The development of peptide-based vaccines against MPXV could offer significant advantages over currently available vaccines, such as no cold chain requirement, stability, and reduced manufacturing costs.

Prolonged immune response to tick-borne Ehrlichia chaffeensis infection using a genetically modified live vaccine.

Ehrlichia chaffeensis, a tick transmitted rickettsial bacterium, causes monocytic ehrlichiosis in humans and dogs. Earlier, we demonstrated that dogs immunized with a mutant strain of E. chaffeensis having a functional disruption in the gene encoding the phage head-to-tail connector protein serves as a modified live vaccine (MLAV) capable of inducing immunity against intravenous and tick-transmitted infection challenges within one month of vaccination. In this follow-up investigation, we assessed the duration of MLAV-induced immunity for one-year period against tick-transmission infection challenge. Dogs vaccinated with the MLAV were subsequently exposed to wild-type E. chaffeensis via tick transmission at 4-, 8-, and 12-months post-vaccination. Unvaccinated controls showed higher infection rates during the one-month assessment following infection. In contrast, MLAV-immunized dogs rapidly cleared infections and exhibited significantly fewer systemic bacterial infections compared to unvaccinated controls. Robust E. chaffeensis-specific IgG and CD4 T-cell responses persisted throughout the assessment period. Our findings underscore the efficacy of MLAV in providing natural hosts with protection against E. chaffeensis infection for up to one year following infected tick exposure.

An attenuated live strain of HY9901 mutant Δgr provides protection against Vibrio alginolyticus in pearl gentian grouper (♀Epinephelus fuscoguttatus × ♂Epinephelus lanceolatu).

Vibrio alginolyticus is a serious aquaculture bacterial pathogen, which is widely distributed in the ocean and rivers, and cause vibriosis in aquaculture. Therefore, it is imperative to develop effective vaccine to prevent vibriosis. In this study, the efficacy of gr deletion strain (Δgr) of V. alginolyticus as an attenuated live vaccine was evaluated in peal gentian grouper by intraperitoneal injection immunization, followed by a wild strain injection challenge. Real-time fluorescence quantitative PCR was used for analyzing the expression dynamics of immune-related genes. ELISA was used to assess the serum antibody titer and non-specific enzyme activities were determined by kit. The results showed that the safe dose of Δgr was 1.0 × 106 CFU/mL for pearl gentian grouper, and the immune protection rate of Δgr was 73.08 %, providing significant protection against V. alginolyticus. The expression levels of all the immune-related genes MHC-Iα, TNF-α, IL-1β, IL-16 and MyD88 were upregulated in liver, spleen, head kidney and thymus within 42 days post-vaccination. In addition, specific antibody IgM, activities of catalase, superoxide dismutase and lysozyme were also significantly increased compared with the control group. It is not only safe for groupers, but also can effectively stimulate both specific and non-specific immunity of fish. These results indicated that Δgr could be used as an effective attenuated live vaccine candidate to prevent pearl gentian grouper against V. alginolyticus in aquaculture.

Spray vaccination with a safe and bivalent H9N2 recombinant chimeric NDV vector vaccine elicits complete protection against NDV and H9N2 AIV challenge

Newcastle disease virus (NDV) and H9N2 avian influenza virus (AIV) represent significant pathogenic risks to the poultry industry, leading to considerable economic losses. Vaccination is a widely used preventive measure against these pathogens, yet the lack of a live bivalent vaccine targeting NDV and H9N2 AIV imposes a heavy vaccination burden. Previously, we constructed a genotype-matched chimeric NDV vector, LX-OAI4S, in which the genotype I NDV backbone was replaced with the ectodomain of haemagglutinin-neuraminidase (HN) and modified using the attenuated F gene from the genotype VII vaccine strain A-VII. Based on the LX-OAI4S vector, we successfully generated three H9N2 recombinant viruses: LX-OAI4S-NPU-HA, LX-OAI4S-MU-HA, and LX-OAI4S-HNU-HA. These recombinants incorporated the H9N2 HA gene, flanked by untranslated regions (UTRs) from the NP, M, or HN gene of the NDV LX strain, inserted between the P and M genes of LX-OAI4S. The vaccine candidate LX-OAI4S-NPU-HA induced a more robust immune response in chickens against H9N2 AIV and NDV than the other two recombinants. This response effectively protects against virus shedding and lethal virus challenge. Furthermore, spray vaccination with LX-OAI4S-NPU-HA showed protective efficacy against H9N2 AIV and NDV. This study offers a promising strategy for comprehensive protection in regions threatened by H9N2 AIV and NDV.

Dengue Vaccination: A Practical Guide for Clinicians

Dengue is a growing global public health challenge, with rising incidence and case fatality rates fueled by urbanization and climate change. The substantial mortality, morbidity, and economic burden associated with the disease underscore the need for effective prevention strategies, including vector control, personal protective measures, and vaccination. This narrative review provides a practical guide for clinicians to ensure the appropriate administration of dengue vaccines to at-risk groups, such as individuals in endemic regions and travelers to these areas. Live-attenuated tetravalent dengue vaccines, including Dengvaxia®, Qdenga®, and Butantan-DV, have demonstrated efficacy in clinical trials but require careful use due to the risk of antibody-dependent enhancement (ADE). To mitigate this risk, guidelines recommend vaccination primarily for individuals with prior confirmed dengue infection, emphasizing the importance of accessible and affordable point-of-care rapid testing. Co-administration of dengue vaccines with other live-attenuated or inactivated vaccines has been shown to be safe and immunogenic, broadening their potential application. However, live-attenuated vaccines are contraindicated for immunocompromised individuals and pregnant women. Enhancing clinician awareness, expanding diagnostic capabilities, and prioritizing high-risk populations are critical steps to optimize vaccination strategies. Combined with robust prevention programs, these efforts are essential to reducing the global burden of dengue and mitigating its impact.

P-1419. Vaccine failure of the live-attenuated vaccine after liver transplantation depends on the vaccine strain

Abstract Background A recent conditional recommendation suggests considering live-attenuated vaccines for solid organ transplant recipients, yet the conditions of their safe and effective administration remain unclear. Primary vaccine failures after the first dose of live-attenuated vaccines (measles, rubella, and mumps) were significantly different between the vaccine strains. Methods This prospective study, conducted at Keio University Hospital from 2002 to August 2023, gave live-attenuated vaccines to liver transplant (LT) recipients fulfilling the criteria for live-attenuated vaccines, including humoral and cell-mediated immunity. Patient background information, immunization date, vaccine strain, immunosuppressive agents at the time of vaccination, and antibody titers were collected. Factors related to primary and secondary vaccine failure were evaluated to enhance the effectiveness of the live-attenuated vaccine program after LT. Kaplan–Meier curves for the proportion of remaining positive antibody titer after the first dose of indicated live-attenuated vaccine for post-liver transplant recipients. Results Among 67 LT recipients, 54, 55, 47, or 55 received at least one dose of live-attenuated vaccine for measles, rubella, varicella, or mumps, respectively. Measles vaccine with the AIK-C strain exhibited significantly lower primary failure rates than the CAM-70 strain (1/38 vs. 4/16, odds ratio: 0.08, 95% confidence interval [CI]: 0.01–0.80, p = 0.02) (Table 1). No primary failures were observed with the TO-336 strain of rubella, whereas 4 of 10 LT recipients with the Matsuura strain of rubella did not seroconvert. For mumps, the Hoshino strain showed lower primary failure rates than the Torii strain (15/52 vs. 3/3, p = 0.03). Among seroconverted LT recipients after the first dose of live-attenuated vaccine, the proportion of remaining positive antibody titer is shown by Kaplan–Meier curves (Figure 1). In the years following the first doses of measles, varicella, and mumps vaccines, the proportion of remaining positive antibody titers decreased gradually. Furthermore, the AIK-C strain exhibited a significantly lower risk of secondary vaccine failure compared to the CAM-70 strain (hazard ratio: 0.29, 95% CI: 0.12–0.72, p = 0.01) (Figure 2). Kaplan–Meier curves for the proportion of remaining positive antibody titer after the first dose of measles vaccine for post-liver transplant recipients with Log-rank test for the vaccine strains. Conclusion Vaccine strains are the most critical factor influencing primary and secondary vaccine failure in post-transplant live-attenuated vaccination. Disclosures Masayoshi Shinjoh, MD, PhD, Meiji Seika Pharma Co., Ltd: Honoraria|Mitsubishi Tanabe Pharma Corporation: Honoraria|MSD K.K.: Honoraria|Pfizer Japan Inc: Advisor/Consultant|Shionogi & Co., Ltd: Honoraria

P-24. Toward the clinical development of ATI-1701, a genetically defined live attenuated tularemia vaccine

Abstract Background Tularemia is a life-threatening disease caused by the bacterium Francisella tularensis. While rare, the disease is notable for its wide host range, low infectious dose, high case fatality rate, and having been previously weaponized. Type A (F. t. tularensis) strains are found predominantly in North America and are generally more virulent than Type B (F. t. holarctica) strains. Both a killed whole cell (KWC) and a live attenuated (LA) vaccine were initially developed and underwent clinical testing in the pre-antibiotic era. While both types of vaccines generated strong antibody responses, later human challenge studies demonstrated that the KWC vaccine failed to protect against aerosol exposure. The LA strain designated LVS, which provided better protection against aerosol challenge but less robust protection against type A strains, was used until recently to immunize laboratory workers. Obstacles for approval of LVS include concerns regarding its undefined attenuation and potential for reversion to virulence. No acellular vaccines have proven to be as effective as LA vaccines. Methods ATI-1701 is a next-generation LA vaccine with a targeted, well-characterized mechanism of attenuation. ATI-1701 carries a clpB gene deletion, which is thought to inhibit its ability to escape from phagosomes, thereby limiting replication in host macrophages. Results Mice immunized ID with 10 CFU of ATI-1701 were fully protected from lethal challenge with the SCHU S4 strain. Rats vaccinated with one dose of ATI-1701 and challenged via aerosol exposure to 5,600 LD50 of virulent SCHU S4 survived infection up to one year post-challenge, whereas all unvaccinated rats died. Regardless of immunizing dose (103-109 CFU), spleens from vaccinated rats contained 103-105 CFU of ATI-1701 14 days after vaccination, and bacteria were cleared from the spleen prior to day 42. Immunization of cynomolgus macaques with a single dose of 105 CFU ATI-1701 protected 80-100% of animals challenged with up to 157,000 LD50 of SCHU S4 via aerosol exposure up to three months after vaccination. One year after vaccination approximately 30% of vaccinated macaques survived challenge whereas control animals died. Conclusion ATI-1701 is a promising tularemia vaccine candidate and is being positioned for a Phase 1 clinical trial. Disclosures All Authors: No reported disclosures

P-606. A Single-round Infectious Virus with Codon-deoptimized Genome: A Powerful Tool for Regulating Pathogenicity of WT/Live-Attenuated Viruses

Abstract Background Coxsackievirus B3 (CVB3) is a ssRNA(+) virus of the Picornaviridae family associated with myocarditis and type I diabetes. Prevention of mother-to-child transmission is important, especially since the outcomes of neonatal infection can be fatal. However, vaccines have not yet been developed. In this study, we revealed that CVB3 codon-deoptimized in the nonstructural proteins’ region (CVB3cd) can be used as live-attenuated vaccines (LAVs). Furthermore, we showed that in co-infection experiments, a CVB3cd-based single-round infectious virus induces interference, significantly reducing the pathogenicity of viruses. Methods CVB3cd were designed to be enriched in CpG-containing rare codons in the 3CD region of the viral genome. Viral proliferation was evaluated based on plaque size and growth curve; and their pathogenicity in mice was determined by weight loss and survival after infection. Defective viral particles (DVPs) were generated by packaging WT or CVB3cd replicons with a trans-expressed viral capsid protein. To evaluate the effect of viral interference with DVPs, WT or CVB3cd were co-administered with the DVPs, and their pathogenicity in mice was monitored. Results A decrease in viral replication was observed in correlation with the number of deoptimized codons, in addition to an increase in the survival rate of animals infected with the codon-deoptimized viruses. Among vaccination methods, intramuscular injection of the attenuated virus emerged as the least pathogenic option, effectively inducing neutralizing antibodies and providing protection against challenge by the WT virus. In addition, simultaneous infection of CVB3 with DVPs revealed that CVB3cd replicon-based DVP (DVPcd), reduced the pathogenicity of CVB3 in mice and improved the safety of LAVs without compromising immunogenicity. Conclusion Our data suggest that viral pathogenicity can be modulated by a combination of codon-deoptimization, route of administration, and viral interference. This approach could be a powerful strategy to develop effective and safe LAVs in a short period of time. Moreover, DVPcd could be used as therapeutic tools against viruses due to their efficient virus-interfering effects. Disclosures Anju Miyamori, Master of Medicine, The research foundation for microbial diseases of Osaka university: Grant/Research Support Hirotaka Ebina, Doctor of Medicine, The research foundation for microbial diseases of Osaka university: Grant/Research Support

595. The Effect of Herpes Zoster Vaccination on New Diagnoses of Dementia: A Quasi-randomized Study in Australia

Abstract Background We have recently provided evidence from a quasi-randomized study in Wales that herpes zoster (HZ) vaccination reduced the incidence of new dementia diagnoses. This study used a similar quasi-randomization in Australia to determine the effect of HZ vaccination on new dementia diagnoses over 7.5 years.Figure 1:Eligibility for a free herpes zoster (HZ) vaccine reduces dementia diagnosesIn panel (a), a regression discontinuity is plotted, where the forcing variable is the number of weeks from the cutoff (November 2, 1936) and the outcome is dementia diagnoses (in percentages). The triangular dots indicate dementia diagnoses for the comparison group, scaled up by the intercept for the main cohort. Panel (b) describes this effect for different follow-up periods, and panel (c) shows the effect for different grace periods. Methods In Australia, starting on November 1 2016, live-attenuated HZ vaccination was provided for free to individuals aged 70 to 79 years of age. Thus, those whose 80th birthday was just a few days prior to November 1 2016 never became eligible, whereas those whose 80th birthday was a few days later were eligible for one year. There is no reason to expect that these population groups who differ in their age by only a minute degree should differ in any of their dementia-related characteristics. We used detailed primary healthcare records (provided by PenCS) with week-of-birth information from 65 general practices across Australia. We analyzed our data using a comparative regression discontinuity design, with dementia diagnoses from older birth cohorts serving as a comparison group. Results Of 108,670 patients in our data, 15,297 were born between November 2 1928 and November 2 1944. At baseline, patients were well-balanced across the date-of-birth eligibility threshold (November 2 1936) for HZ vaccination in their preventive health services uptake and chronic disease diagnoses. There was an abrupt increase of 13.2 (95% CI: [8.7, 17.6], p = 0.001) percentage points in the probability of ever receiving HZ vaccination between patients born shortly before versus shortly after the eligibility threshold. Eligibility for a free HZ vaccination caused a 3.9 percentage point (95% CI: [1.7, 6.1], p = 0.001) decrease in the probability of receiving a new dementia diagnosis over 7.5 years. Being eligible for HZ vaccination did not affect the probability of taking up other preventive health services (including other vaccinations) nor do we find consistent evidence that it affected the probability of receiving any of the twenty most common disease diagnoses in our data. Conclusion In conjunction with our findings from Wales, these results from Australia constitute robust evidence that live-attenuated HZ vaccination may delay or prevent dementia. Disclosures All Authors: No reported disclosures

P-2346. Mpox-Specific Cellular and Humoral immunity in Mpox-Survivors Living With HIV

Abstract Background Mpox is an orthopoxvirus with a rodent reservoir that causes a disease similar to mild smallpox. In 2022, a sexually-transmitted global mpox outbreak infected over 90,000 individuals. Some immunocompromised patients experienced prolonged, severe mpox resulting in significant morbidity, amputations, and death. People living with HIV (PLWH) were at particularly high risk due to impaired cell-mediated immunity, as CD4 and CD8 T-cells help eradicate the virus from infected lesions. Mpox virion total binding titer in PLWH with or without history of mpox infection Methods We compared immune responses to mpox in PLWH who were either mpox-naïve (n = 10) versus mpox-survivors (n = 15). We measured total mpox antibody levels with a novel ELISA assay using lysed mpox virions. We characterized mpox and orthopoxvirus-specific cell-mediated immunity using intracellular cytokine staining with an enhanced protocol to allow detection of low-frequency cellular populations. Poxvirus-specific T-cell responses in PLWH as determined by intracellular cytokine stimulation using live vaccinia virus (MVA), conserved orthopoxvirus peptide pools (VCD4 and VCD8), and mpox-specific peptide pools (MCD4 and MCD8). Pools provided by Alba Grifoni and Alessandro Sette (La Jolla Institute). Interferon-gamma (IFNγ), tumor necrosis factor alpha (TNFα), and interleukin 2 (IL-2) were the predominant cytokines detected. Responders defined as having any CD4 or CD8 response for any of the 9 stimulations above the 90th percentile of the control group. Results Our assays differentiated well between the mpox-naïve and mpox-survivors. All mpox-survivors had binding titers of 10 to 1,000 times background with no antibodies detected in mpox-uninfected PLWH. Mpox-specific CD4 and CD8 responses of 0.01 to 0.3% were present in all infected individuals, comparable to immunocompetent mpox-survivors. The magnitude of mpox-specific T-cell responses correlated well with vaccinia-specific T-cell responses, demonstrating induction of broad anti-orthopoxvirus cell-mediated immunity. CD4 T-cell responses were TH1-type, with higher polyfunctionality in mpox-specific T-cells compared to HIV and CMV-specific T-cells. The magnitude of the IFNγ and TNFα CD4 and CD8 responses correlated with mpox-binding antibody titers, but did not predict cross-neutralization titers from vaccinia, a closely related virus that is used to vaccinate for smallpox and mpox. Host CD4 count did not correlate with the magnitude of mpox-specific cellular or humoral immunity. Conclusion These new assays effectively quantify and characterize mpox-specific immunity, with strong induction of orthopoxvirus-specific humoral and cellular immunity in immunocompromised hosts with HIV. Although PLWH are at increased risk for complications from mpox, their potent immune responses post-infection suggest that most are at reduced risk for severe complications from re-infection. Disclosures Samuel D. Stampfer, MD/PhD, Gilead: Stocks/Bonds (Public Company) Colleen F. Kelley, MD, MPH, Gilead: Grant/Research Support|Humanigen: Grant/Research Support|Moderna: Grant/Research Support|Novavax: Grant/Research Support|ViiV: Grant/Research Support

Improved Protective Efficacy in Rainbow Trout (Oncorhynchus mykiss) Against Vibrio anguillarum Through Immunization with a Combination of Formalin-Killed and Auxotrophic-Live V. anguillarum.

Vibriosis caused by Vibrio anguillarum has been an important bacterial disease in cultured rainbow trout (Oncorhynchus mykiss). In the present study, we evaluated the protective efficacy of a vaccine that consists of formalin-killed (FK) V. anguillarum and the alr genes knockout auxotrophic-live (AL) V. anguillarum (Δalr1Δalr2 V. anguillarum). Fish were immunized with a high dose of the FK V. anguillarum vaccine or four different combinations of FK and AL V. anguillarum. In the challenge test, fish immunized with 1 × 106CFU of FK V. anguillarum plus 1 × 104CFU of AL V. anguillarum (FK-106 + AL-104) showed complete protection (100% RPS) against V. anguillarum. In comparison, fish immunized with 1 × 107CFU of FK V. anguillarum (FK-107) showed much lower survival rates. In the result of ELISA, the antibody titer of fish immunized with FK-106 + AL-104 was significantly higher than that of the PBS group, but the titer was not higher than FK-107, suggesting that the higher protection by the FK + AL combination vaccine might be mediated by not only humoral immunity but also other protective factors conferred by live bacteria in the combination vaccine. In conclusion, the present FK + AL combination vaccine efficiently protected rainbow trout with approximately 10 times lower doses of bacteria than FK-107, which could lessen the safety problem caused by a high-tittered live bacteria vaccine and the lower immunogenicity problem of killed bacteria vaccine.

The Current Status in Terms of Vaccination for Individuals Infected with Human Immunodeficiency Virus

Human immunodeficiency virus (HIV)-infected individuals have an increased risk of various infections due to their impaired host immune system, resulting in higher morbidity and mortality rates. These patients severely suffered during the COVID-19 epidemic, the influenza epidemic and the spread of monkeypox. Reducing serious infections is one of the most important measures to improve HIV-infected individuals’ quality and length of life. Based on the preparation processes and their antigenic properties, vaccines are divided into several types, including inactivated vaccines, attenuated live vaccines, recombinant protein vaccines, toxoid vaccines, polysaccharide vaccines, polysaccharide (protein) combined vaccines, nucleic acid vaccines, viral vector vaccines, etc. With the innovation of vaccine preparation technology in recent years and the acceleration of vaccine approval and market launch, more and more vaccine products suitable for HIV-infected individuals have become available. Because of their deficient immune systems, the type of vaccines and the schedule of vaccinations available to individuals living with HIV are sometimes different from those with healthy immune systems. This article reviewed the current status of vaccination in and shed light on the vaccination strategies for HIV-infected persons in terms of their safety and effectiveness.

Multiple gene-deletion vaccinia virus Tiantan strain against mpox

Monkeypox virus (MPXV) is an important zoonotic pathogenic virus, which poses serious threats to public health. MPXV infection can be prevented by immunization against the variola virus. Because of the safety risks and side effects of vaccination with live vaccinia virus (VACV) strain Tian Tan (VTT), we constructed two gene-deleted VTT recombinants (TTVAC7 and TTVC5). The immunogenicity and protective effects of the gene-deleted VTT vaccine were assessed using BALB/C mice challenged with VTT and New Zealand rabbits challenged with MPXV. The results demonstrated strong humoral and cellular immune responses. The VTT-specific and neutralizing antibody titers, specific T cell levels, and degree of dendritic cell maturation of the mice, in addition to the MPXV neutralizing antibody titers and IFN-γ, IL-6, and TNF-α levels of the rabbits were markedly higher in the groups immunized with TTVAC7 and TTVC5 than the control groups (p < 0.05). Moreover, immunization with TTVAC7 and TTVC5 reduced morbidities caused by VACV and MPXV infection. The weight change, lung histological score, and residual virus of the mouse model (p < 0.05). Similarly, the temperature change, pock number, lung histological score, and residual virus of the rabbit model were significantly reduced in the groups immunized with TTVAC7 and TTVC5 (p < 0.05). Collectively, these results demonstrate that TTVAC7 and TTVC5 may be used as potential live attenuated vaccines against MPXV infection.

Clinical assessment and transcriptome analysis of host immune responses in a vaccination-challenge study using a glycoprotein G deletion mutant vaccine strain of infectious laryngotracheitis virus

A glycoprotein-G-deleted live-attenuated vaccine strain of the infectious laryngotracheitis virus (ILTV), ΔgG-ILTV, is safe and efficacious against ILTV challenge. In the current study, the transcriptome of peripheral blood mononuclear cells (PBMCs) of the ΔgG-ILTV-vaccinated group of specific-pathogen-free chickens were compared to those of the nonvaccinated group at 7 days post-vaccination. Tracheal transcriptomes after challenge with virulent ILTV were compared between groups of the non-vaccinated-challenged and the vaccinated-challenged as well as the non-vaccinated-challenged and the uninfected chickens at 4 to 5 days post-challenge. The clinical outcomes after challenge between these groups were also evaluated. Significant differences were observed in the tracheal transcriptome of the non-vaccinated-challenged birds compared to the other two groups. Enriched gene ontologies and pathways that indicated heightened immune responses and impairments to ciliary and neuronal functions, cell junction components, and potential damages to cartilaginous and extracellular components in the trachea of the non-vaccinated-challenged birds were consistent with their severe tracheal pathology compared to the other two groups. On the contrary, the absence of any difference in the tracheal transcriptome between the vaccinated-challenged and the uninfected birds were reflected by the preservation of tracheal mucosal integrity in both groups and mild infiltration of leukocytes in the vaccinated-challenged birds. The results from this study demonstrated that vaccination with ΔgG-ILTV prevented the changes in tracheal transcriptome induced during ILTV challenge, resulting in clinical protection. Additionally, these results also provide insights into the molecular mechanisms underlying the tracheal pathology induced by ILTV infection.