Evaluation of the immunogenicity of an mRNA vectored Nipah virus vaccine candidate in pigs.

Nipah virus (NiV) poses a significant threat to human and livestock populations across South and Southeast Asia. Vaccines are required to reduce the risk and impact of spillover infection events. Pigs can act as an intermediate amplifying host for NiV and, separately, provide a preclinical model for evaluating human vaccine candidate immunogenicity. The aim of this study was therefore to evaluate the immunogenicity of an mRNA vectored NiV vaccine candidate in pigs. Pigs were immunized twice with 100 µg nucleoside-modified mRNA vaccine encoding soluble G glycoprotein from the Malaysia strain of NiV, formulated in lipid nanoparticles. Potent antigen-binding and virus neutralizing antibodies were detected in serum following the booster immunization. Antibody responses effectively neutralized both the Malaysia and Bangladesh strains of NiV but showed limited neutralization of the related (about 80% amino acid sequence identity for G) Hendra virus. Antibodies were also capable of neutralizing NiV glycoprotein mediated cell-cell fusion. NiV G-specific T cell cytokine responses were also measurable following the booster immunization with evidence for induction of both CD4 and CD8 T cell responses. These data support the further evaluation of mRNA vectored NiV G as a vaccine for both pigs and humans.

Safety and Efficacy of the Modified Vaccinia Ankara-Bavaria Nordic Vaccine Against Mpox in the Real World: Systematic Review and Meta-Analysis.

In May 2022, mpox began to spread worldwide, posing a serious threat to human public health. Modified Vaccinia Ankara-Bavaria Nordic (MVA-BN) is a live attenuated orthopoxvirus vaccine that has been authorized by the U.S. Food and Drug Administration as the vaccine of choice for the prevention of mpox. In this study, we conducted a meta-analysis of all currently published literature on the efficacy and safety of the MVA-BN vaccine in the real world, showing that the MVA-BN vaccine is effective and safe, with efficacy of up to 75% with a single dose and up to 80% with a two-dose vaccine. Meanwhile, we found that subcutaneous injection has lower local and systemic adverse events than intradermal injection, regardless of single- or two-dose vaccination, and subcutaneous injection is better tolerated in children, the elderly, or people with underlying medical conditions. These results have important reference value for clinical practice.

Saccharomyces cerevisiae oral immunization in mice using multi-antigen of the African swine fever virus elicits a robust immune response.

African swine fever virus (ASFV) is one of the most complex viruses. ASFV is a serious threat to the global swine industry because no commercial vaccines against this virus are currently available except in Vietnam. Moreover, ASFV is highly stable in the environment and can survive in water, feed, and aerosols for a long time. ASFV is transmitted through the digestive and respiratory tract. Mucosal immunity is the first line of defense against ASFV. Saccharomyces cerevisiae (SC), which has been certified by the U.S. Food and Drug Administration and has a generally recognized as safe status in the food industry, was used for oral immunization in this study. ASFV antigens were effectively expressed in recombinant SC strains with high DNA copy numbers and stable growth though surface display technology and chromosome engineering (δ-integration). The recombinant SC strains containing eight ASFV antigens-KP177R, E183L, E199L, CP204L, E248R, EP402R, B602L, and B646L- induced strong humoral and mucosal immune responses in mice. There was no antigenic competition, and these antigens induced Th1 and Th2 cellular immune responses. Therefore, the oral immunization strategy using recombinant SC strains containing multiple ASFV antigens demonstrate potential for future testing in swine, including challenge studies to evaluate its efficacy as a vaccine against ASFV.

A combined cross-sectional analysis and case-control study evaluating tick-borne encephalitis vaccination coverage, disease and vaccine effectiveness in children and adolescents, Switzerland, 2005 to 2022.

BackgroundTick-borne encephalitis (TBE) is a severe, vaccine-preventable viral infection of the central nervous system. Symptoms are generally milder in children and adolescents than in adults, though severe disease does occur. A better understanding of the disease burden and duration of vaccine-mediated protection is important for vaccination recommendations.AimTo estimate TBE vaccination coverage, disease severity and vaccine effectiveness (VE) among individuals aged 0-17 years in Switzerland.MethodsVaccination coverage between 2005 and 2022 was estimated using the Swiss National Vaccination Coverage Survey (SNVCS), a nationwide, repeated cross-sectional study assessing vaccine uptake. Incidence and severity of TBE between 2005 and 2022 were determined using data from the Swiss disease surveillance system and VE was calculated using a case-control analysis, matching TBE cases with SNVCS controls.ResultsOver the study period, vaccination coverage increased substantially, from 4.8% (95% confidence interval (CI): 4.1-5.5%) to 50.1% (95% CI: 48.3-52.0%). Reported clinical symptoms in TBE cases were similar irrespective of age. Neurological involvement was less likely in incompletely (1-2 doses) and completely (≥ 3 doses) vaccinated cases compared with unvaccinated ones. For incomplete vaccination, VE was 66.2% (95% CI: 42.3-80.2), whereas VE for complete vaccination was 90.8% (95% CI: 87.7-96.4). Vaccine effectiveness remained high, 83.9% (95% CI: 69.0-91.7) up to 10 years since last vaccination.ConclusionsEven children younger than 5 years can experience severe TBE. Incomplete and complete vaccination protect against neurological manifestations of the disease. Complete vaccination offers durable protection up to 10 years against TBE.

Nucleic acid vaccine candidates encapsulated with mesoporous silica nanoparticles against MERS-CoV.

Middle East respiratory coronavirus (MERS-CoV) is a newly emergent, highly pathogenic coronavirus that is associated with 34% mortality rate. MERS-CoV remains listed as priority pathogen by the WHO. Since its discovery in 2012 and despite the efforts to develop coronaviruses vaccines to fight against SARS-CoV-2, there are currently no MERS-CoV vaccine that has been approved. Therefore, there is high demand to continue on the development of prophylactic vaccines against MERS-CoV. Current advancements in vaccine developments can be adapted for the development of improved MERS-CoV vaccines candidates. Nucleic acid-based vaccines, including pDNA and mRNA, are relatively new class of vaccine platforms. In this work, we developed pDNA and mRNA vaccine candidates expressing S.FL gene of MERS-CoV. Further, we synthesized a silane functionalized hierarchical aluminosilicate to encapsulate each vaccine candidates. We tested the nucleic acid vaccine candidates in mice and evaluated humoral antibodies response. Interestingly, we determined that the non-encapsulated, codon optimized S.FL pDNA vaccine candidate elicited the highest level of antibody responses against S.FL and S1 of MERS-CoV. Encapsulation of mRNA with nanoporous aluminosilicate increased the humoral antibody responses, whereas encapsulation of pDNA did not. These findings suggests that MERS-CoV S.FL pDNA vaccine candidate induced the highest level of humoral responses. This study will enhance further optimization of nanosilica as potential carrier for mRNA vaccines. In conclusion, this study suggests MERS-CoV pDNA vaccine candidate as a suitable vaccine platform for further pivotal preclinical testings.

Postvaccination serosurveillance of foot-and-mouth disease through virus-neutralizing and nonstructural protein antibody tests on pig farms in Taiwan: 2009-2020.

The use of virus-neutralizing (VN) and nonstructural protein (NSP) antibody tests in a serosurveillance program for foot-and-mouth disease (FMD) can identify pig herds that are adequately vaccinated, with a high percentage of pigs with VN positive antibody titers; these tests can also help identify pigs with NSP-positivity that have previously been or are currently infected even in vaccinated herds. To identify infected herds and manage infection, the combination of VN and NSP antibody tests was used in Taiwan's serosurveillance program implemented simultaneously with the compulsory FMD vaccination program. The result was the eradication of FMD: Taiwan was recognized by the World Organization for Animal Health as an FMD-free country without vaccination in 2020. Evaluation of the compulsory vaccination program incorporated in the FMD control program in Taiwan revealed that the vaccine quality was satisfactory and the vaccination program was effective during the period of compulsory vaccination (2010-2017). Sound immunological coverage was achieved, with 89.1% of pigs having VN antibody titers exceeding 1:16 in 2016. This level of immunological coverage would be expected to substantially reduce or prevent FMD transmission, which was borne out by the results of the NSP tests. We identified farms having positive NSP reactors (very low annual prevalence) before the cessation of FMD vaccination in July 2018; however, detailed serological and clinical investigations of pigs of all ages in suspect herds demonstrated that no farms were harboring infected animals after the second half of 2013. Thus, the results revealed no evidence of FMD circulation in the field, and Taiwan regained FMD-free status.

Investigation of the safety and protective efficacy of an attenuated and marker M. bovis-BoHV-1 combined vaccine in bovines.

Bovine respiratory disease (BRD) is one of the most common diseases in the cattle industry worldwide; it is caused by multiple bacterial or viral coinfections, of which Mycoplasma bovis (M. bovis) and bovine herpesvirus type 1 (BoHV-1) are the most notable pathogens. Although live vaccines have demonstrated better efficacy against BRD induced by both pathogens, there are no combined live and marker vaccines. Therefore, we developed an attenuated and marker M. bovis-BoHV-1 combined vaccine based on the M. bovis HB150 and BoHV-1 gG-/tk- strain previously constructed in our lab and evaluated in rabbits. This study aimed to further evaluate its safety and protective efficacy in cattle using different antigen ratios. After immunization, all vaccinated cattle had a normal rectal temperature and mental status without respiratory symptoms. CD4+, CD8+, and CD19+ cells significantly increased in immunized cattle and induced higher humoral and cellular immune responses, and the expression of key cytokines such as IL-4, IL-12, TNF-α, and IFN-γ can be promoted after vaccination. The 1.0 × 108 CFU of M. bovis HB150 and 1.0 × 106 TCID50 BoHV-1 gG-/tk- combined strain elicited the most antibodies while significantly increasing IgG and cellular immunity after challenge. In conclusion, the M. bovis HB150 and BoHV-1 gG-/tk- combined strain was clinically safe and protective in calves; the mix of 1.0 × 108 CFU of M. bovis HB150 and 1.0 × 106 TCID50 BoHV-1 gG-/tk- strain was most promising due to its low amount of shedding and highest humoral and cellular immune responses compared with others. This study introduces an M. bovis-BoHV-1 combined vaccine for application in the cattle industry.

Oral administration of PEDV-dissolved Alg-CS gel induces high and sustained mucosal immunity in mice.

Porcine epidemic diarrhea (PED) is a serious disease in piglets that leads to high mortality. An effective measure that provides higher IgA levels in the intestine and milk is required to decrease losses. Porcine epidemic diarrhea virus (PEDV) was dissolved in calcium alginate (Alg) and combined with chitosan (CS) via electrostatic interactions between cationic chitosan and anionic alginate to create a porous gel (Alg-CS+PEDV). The gel was used to immunize mice orally or in combination with subcutaneous injections of inactivated PEDV vaccine. At 12 and 24 days after immunization, levels of IgA and IgG in Alg-CS+PEDV were higher than with normal PEDV oral administration. At 24 days after immunization, the concentration of IFN-γ in Alg-CS+PEDV was higher than with normal PEDV oral administration. Furthermore, oral administration combining subcutaneous immunization induced higher levels of IgG and IgA than oral administration alone. Our study provides a new method for the preparation and administration of oral vaccines to achieve enhanced mucosal immunity against PEDV.

A measles-vectored vaccine candidate expressing prefusion-stabilized SARS-CoV-2 spike protein brought to phase I/II clinical trials: protection of African green monkeys from COVID-19 disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged at the end of 2019 and is responsible for the largest human pandemic in 100 years. Thirty-four vaccines are currently approved for use worldwide, and approximately 67% of the world population has received a complete primary series of one, yet countries are dealing with new waves of infections, variant viruses continue to emerge, and breakthrough infections are frequent secondary to waning immunity. Here, we evaluate a measles virus (MV)-vectored vaccine expressing a stabilized prefusion SARS-CoV-2 spike (S) protein (MV-ATU3-S2PΔF2A; V591) with demonstrated immunogenicity in mouse models (see companion article [J. Brunet, Z. Choucha, M. Gransagne, H. Tabbal, M.-W. Ku et al., J Virol 98:e01693-23, 2024, https://doi.org/10.1128/jvi.01693-23]) in an established African green monkey model of disease. Animals were vaccinated with V591 or the control vaccine (an equivalent MV-vectored vaccine with an irrelevant antigen) intramuscularly using a prime/boost schedule, followed by challenge with an early pandemic isolate of SARS-CoV-2 at 56 days post-vaccination. Pre-challenge, only V591-vaccinated animals developed S-specific antibodies that had virus-neutralizing activity as well as S-specific T cells. Following the challenge, V591-vaccinated animals had lower infectious virus and viral (v) RNA loads in mucosal secretions and stopped shedding virus in these secretions earlier. vRNA loads were lower in these animals in respiratory and gastrointestinal tract tissues at necropsy. This correlated with a lower disease burden in the lungs as quantified by PET/CT at early and late time points post-challenge and by pathological analysis at necropsy.IMPORTANCESevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the largest human pandemic in 100 years. Even though vaccines are currently available, countries are dealing with new waves of infections, variant viruses continue to emerge, breakthrough infections are frequent, and vaccine hesitancy persists. This study uses a safe and effective measles vaccine as a platform for vaccination against SARS-CoV-2. The candidate vaccine was used to vaccinate African green monkeys (AGMs). All vaccinated AGMs developed robust antigen-specific immune responses. After challenge, these AGMs produced less virus in mucosal secretions, for a shorter period, and had a reduced disease burden in the lungs compared to control animals. At necropsy, lower levels of viral RNA were detected in tissue samples from vaccinated animals, and the lungs of these animals lacked the histologic hallmarks of SARS-CoV-2 disease observed exclusively in the control AGMs.

Phase 3 immunogenicity and safety study of a tick-borne encephalitis vaccine in healthy Japanese participants 1 year of age and older.

BACKGROUND: Tick-borne encephalitis (TBE) virus infects the central nervous system and may lead to severe neurological complications or death. This study assessed immunogenicity, safety, and tolerability of TBE vaccine in Japanese participants 1 year of age and older. METHODS: This phase 3, multicenter, single-arm, open-label study was conducted in Japanese adult (≥ 16 years) and pediatric (1-< 16 years) populations. Participants received a single 0.5-mL (adult) or 0.25-mL (pediatric) dose of TBE vaccine at each of 3 visits. The primary endpoint was the proportion of participants who were seropositive (neutralization test [NT] titer ≥ 1:10) 4 weeks after Dose 3. Secondary and exploratory endpoints included NT seropositivity rates 4 weeks after Dose 2, immunoglobulin G (IgG) seropositivity 4 weeks after Doses 2 and 3, NT geometric mean titers (GMTs), IgG geometric mean concentrations (GMCs), and geometric mean fold rises. Primary safety endpoints were frequencies of local reactions, systemic events, adverse events (AEs), and serious AEs. RESULTS: Among 100 adult and 65 pediatric participants, 99.0 % and 100.0 % completed the study, respectively. NT seropositivity was achieved in 98.0 % adult and 100.0 % pediatric participants after Dose 3; seropositivity after Dose 2 was 93.0 % and 92.3 %, respectively. In both age groups, IgG seropositivity was ≥ 90.0 % and ≥ 96.0 % after Doses 2 and 3, respectively; GMTs and GMCs were highest 4 weeks after Dose 3. Reactogenicity events were generally mild to moderate in severity and short-lived. AEs were reported by 15.0 % (adult) and 43.1 % (pediatric) of participants. No life-threatening AEs, AEs leading to discontinuation, immediate AEs, related AEs, or deaths were reported. No serious AEs were considered related to TBE vaccine. CONCLUSIONS: TBE vaccine elicited robust immune responses in Japanese participants 1 year of age and older. The 3-dose regimen was safe and well tolerated, and findings were consistent with the known safety profile of this TBE vaccine. CLINICALTRIALS: gov: NCT04648241.

Vaccination against Rabbit Hemorrhagic Disease Virus 2 (RHDV2) Using a Baculovirus Recombinant Vaccine Provides Durable Immunity in Rabbits.

Rabbit hemorrhagic disease virus 2 (RHDV2) emerged in the United States in 2018 and has spread in both domestic and wild rabbits nationwide. The virus has a high mortality rate and can spread rapidly once introduced in a rabbit population. Vaccination against RHDV2 provides the best protection against disease and should be considered by all rabbit owners. Here, we investigate the duration of immunity provided by vaccination with the Medgene Platform conditionally licensed commercial vaccine 6 months following the initial series. Rabbits received either the vaccination or a placebo and were challenged with RHDV2 6 months later. All vaccinated rabbits survived challenge whereas 18/19 non-vaccinated controls succumbed to infection within 10 or fewer days post-challenge. These results demonstrate lasting immunity following vaccination with the Medgene RHDV2 vaccine.

The mRNA Vaccine Expressing Single and Fused Structural Proteins of Porcine Reproductive and Respiratory Syndrome Induces Strong Cellular and Humoral Immune Responses in BalB/C Mice.

PRRS is a viral disease that profoundly impacts the global swine industry, causing significant economic losses. The development of a novel and effective vaccine is crucial to halt the rapid transmission of this virus. There have been several vaccination attempts against PRRSV using both traditional and alternative vaccine design development approaches. Unfortunately, there is no currently available vaccine that can completely control this disease. Thus, our study aimed to develop an mRNA vaccine using the antigens expressed by single or fused PRRSV structural proteins. In this study, the nucleotide sequence of the immunogenic mRNA was determined by considering the antigenicity of structural proteins and the stability of spatial structure. Purified GP5 protein served as the detection antigen in the immunological evaluation. Furthermore, cellular mRNA expression was detected by immunofluorescence and western blotting. In a mice experiment, the Ab titer in serum and the activation of spleen lymphocytes triggered by the antigen were detected by ELISA and ICS, respectively. Our findings demonstrated that both mRNA vaccines can significantly stimulate cellular and humoral immune responses. More specifically, the GP5-mRNA exhibited an immunological response that was similar to that of the commercially available vaccine when administered in high doses. To conclude, our vaccine may show promising results against the wild-type virus in a natural host.

A Bacterium-like Particle Vaccine Displaying Envelope Proteins of Canine Distemper Virus Can Induce Immune Responses in Mice and Dogs.

Canine distemper virus (CDV) can cause fatal infections in giant pandas. Vaccination is crucial to prevent CDV infection in giant pandas. In this study, two bacterium-like particle vaccines F3-GEM and H4-GEM displaying the trimeric F protein or tetrameric H protein of CDV were constructed based on the Gram-positive enhanced-matrix protein anchor (GEM-PA) surface display system. Electron microscopy and Western blot results revealed that the F or H protein was successfully anchored on the surface of GEM particles. Furthermore, one more bacterium-like particle vaccine F3 and H4-GEM was also designed, a mixture consisting of F3-GEM and H4-GEM at a ratio of 1:1. To evaluate the effect of the three vaccines, mice were immunized with F3-GEM, H4-GEM or F3 and H4-GEM. It was found that the level of IgG-specific antibodies and neutralizing antibodies in the F3 and H4-GEM group was higher than the other two groups. Additionally, F3 and H4-GEM also increased the secretion of Th1-related and Th2-related cytokines. Moreover, F3 and H4-GEM induce IgG and neutralizing antibodies' response in dogs. Conclusions: In summary, F3 and H4-GEM can provoke better immune responses to CDV in mice and dogs. The bacterium-like particle vaccine F3 and H4-GEM might be a potential vaccine candidate for giant pandas against CDV infection.

Mitigation of False Layer Syndrome Through Maternal Antibodies Against Infectious Bronchitis Virus.

The relationship between passive immunity and the development of false layer syndrome (FLS) and its associated lesions was investigated in this study by comparing the long-term reproductive effects of an infectious bronchitis virus (IBV) DMV/1639 wild-type strain and the GA08 vaccine in birds with and without maternal antibodies. There was a clear protective effect provided by maternal antibodies against both the early vaccination and challenge. It was also observed that vaccination at an early age, in the absence of maternal antibodies, can induce reproductive issues, such as reduced egg production and FLS-associated lesions (e.g., cystic oviduct and egg yolk coelomitis). This might indicate that maternal antibodies and the timing of IBV infection are more important in the generation of FLS than the IBV strain type.

Mitigación del síndrome de la falsa ponedora mediante anticuerpos maternos contra el virus de la bronquitis infecciosa. En este estudio se investigó la relación entre la inmunidad pasiva y el desarrollo del síndrome de la falsa ponedora (FLS) y sus lesiones asociadas comparando los efectos reproductivos a largo plazo de una cepa de tipo silvestre DMV/1639 del virus de la bronquitis infecciosa (IBV) y la cepa vacunal GA08, en aves con y sin anticuerpos maternos. Hubo un claro efecto protector proporcionado por los anticuerpos maternos tanto contra la vacunación temprana como contra el desafío. También se observó que la vacunación a una edad temprana, en ausencia de anticuerpos maternos, puede inducir problemas reproductivos, como una reducción de la producción de huevo y lesiones asociadas al síndrome de la falsa ponedora (p. ej., oviducto quístico y celomitis de yema de huevo). Esto podría indicar que los anticuerpos maternos y el momento de la infección por el virus de la bronquitis infecciosa son más importantes en la generación del síndrome de la falsa ponedora que el tipo de cepa del virus de la bronquitis infecciosa.

Protective Efficacy of Lyophilized Vesicular Stomatitis Virus-Based Vaccines in Animal Model.

We evaluated the in vitro effects of lyophilization for 2 vesicular stomatitis virus-based vaccines by using 3 stabilizing formulations and demonstrated protective immunity of lyophilized/reconstituted vaccine in guinea pigs. Lyophilization increased stability of the vaccines, but specific vesicular stomatitis virus-based vaccines will each require extensive analysis to optimize stabilizing formulations.

Orf virus as an adjuvant enhances the immune response to a PCV2 subunit vaccine.

Orf virus (ORFV), a member of the genus Parapoxvirus, possesses an excellent immune activation capability, which makes it a promising immunomodulation agent. In this study, we evaluated ORFV as a novel adjuvant to enhance the immune response of mice to a subunit vaccine using porcine circovirus type 2 (PCV2) capsid (Cap) protein as a model. Our results showed that both inactivated and live attenuated ORFV activated mouse bone marrow-derived dendritic cells and increased expression of immune-related cytokines interleukin (IL)-1ß, IL-6, and TNF-α. Enhanced humoral and cellular immune responses were induced in mice immunized with PCV2 Cap protein combined with inactivated or live attenuated ORFV adjuvant compared with the aluminum adjuvant. Increased secretion of Th1 and Th2 cytokines by splenic lymphocytes in immunized mice further indicated that the ORFV adjuvant promoted a mixed Th1/Th2 immune response. Moreover, addition of the ORFV adjuvant to the PCV2 subunit vaccine significantly reduced the viral load in the spleen and lungs of PCV2-challenged mice and prevented pathological changes in lungs. This study demonstrates that ORFV enhances the immunogenicity of a PCV2 subunit vaccine by improving the adaptive immune response, suggesting the potential application of ORFV as a novel adjuvant.

Live-attenuated CHIKV vaccine with rearranged genome replicates in vitro and induces immune response in mice.

Chikungunya fever virus (CHIKV) is a mosquito-borne alphavirus that causes wide-spread human infections and epidemics in Asia, Africa and recently, in the Americas. CHIKV is considered a priority pathogen by CEPI and WHO. Despite recent approval of a live-attenuated CHIKV vaccine, development of additional vaccines is warranted due to the worldwide outbreaks of CHIKV. Previously, we developed immunization DNA (iDNA) plasmid capable of launching live-attenuated CHIKV vaccine in vivo. Here we report the use of CHIKV iDNA plasmid to prepare a novel, live-attenuated CHIKV vaccine V5040 with rearranged RNA genome. In V5040, genomic RNA was rearranged to encode capsid gene downstream from the glycoprotein genes. Attenuated mutations derived from experimental CHIKV 181/25 vaccine were also engineered into E2 gene of V5040. The DNA copy of rearranged CHIKV genomic RNA with attenuated mutations was cloned into iDNA plasmid pMG5040 downstream from the CMV promoter. After transfection in vitro, pMG5040 launched replication of V5040 virus with rearranged genome and attenuating E2 mutations. Furthermore, V5040 virus was evaluated in experimental murine models for general safety and immunogenicity. Vaccination with V5040 virus subcutaneously resulted in elicitation of CHIKV-specific, virus-neutralizing antibodies. The results warrant further evaluation of V5040 virus with rearranged genome as a novel live-attenuated vaccine for CHIKV.

No vaccine interference between bovine coronavirus and bovine herpesvirus-1 in a randomized trial when coadministrating two intranasal modified-live viral vaccines to neonatal calves.

OBJECTIVE: Compare immune responses induced by 2 commercial intranasal (IN) modified-live viral (MLV) vaccines given individually or coadministered and evaluate prevention of infection and lung pathology following bovine herpesvirus-1 (BHV-1) challenge. ANIMALS: 36 male Holstein calves (ages, 5 to 12 days). METHODS: In a randomized complete block design, each calf received an IN injection of either vaccine diluent (Placebo), an MLV vaccine containing bovine herpesvirus-1 (BHV-1; N3), bovine coronavirus vaccine (BC), or both N3 and BC (BC + N3) with a booster 4 weeks later. Nasal secretions and blood were collected weekly. Three weeks after the booster, the calves were challenged with BHV-1, sampled for virus shedding, and euthanized 10 days later to quantify lung pathology. The study period was September 7, 2020, to April 6, 2021. RESULTS: Calves were seropositive for BHV-1 and BC before vaccination. No significant difference in BC-specific serum immunoglobin G and nasal immunoglobin A antibody responses in the BC versus BC + N3 group or BHV-1-specific serum immunoglobin G and nasal immunoglobin A antibody responses in the N3 versus BC + N3 group. Cytokine responses to BHV-1 and BC did not differ among groups. BHV-1 shedding after challenge was significantly reduced in N3 groups versus Placebo and BC. There was a significant reduction in lung pathology in the N3 + BC group versus Placebo. CLINICAL RELEVANCE: This study provides evidence an MLV vaccine containing BHV-1 and an MLV BC vaccine can be coadministered to neonatal calves without significantly altering immune responses to the 2 viruses or compromising the prevention of BHV-1 respiratory disease. Calves receiving the BC + N3 vaccine had a significant reduction in lung pathology after BHV-1 aerosol challenge.

Intranasal booster vaccination of beef steers reduces clinical signs following experimental coinfection with BRSV and BHV-1 without reducing shedding of BRD-associated bacteria.

OBJECTIVE: To determine the efficacy of primary or booster intranasal vaccination of beef steers on clinical protection and pathogen detection following simultaneous challenge with bovine respiratory syncytial virus and bovine herpes virus 1. METHODS: 30 beef steers were randomly allocated to 3 different treatment groups starting at 2 months of age. Group A (n = 10) was administered a single dose of a parenteral modified-live vaccine and was moved to a separate pasture. Groups B (n = 10) and C (10) remained unvaccinated. At 6 months of age, all steers were weaned and transported. Subsequently, groups A and B received a single dose of an intranasal modified-live vaccine vaccine while group C remained unvaccinated. Group C was housed separately until challenge. Two days following vaccination, all steers were challenged with bovine respiratory syncytial virus and bovine herpes virus 1 and housed in a single pen. Clinical and antibody response outcomes and the presence of nasal pathogens were evaluated. RESULTS: The odds of clinical disease were lower in group A compared with group C on day 7 postchallenge; however, antibody responses and pathogen detection were not significantly different between groups before and following viral challenge. All calves remained negative for Histophilus somni and Mycoplasma bovis; however, significantly greater loads of Mannheimia haemolytica and Pasteurella multocida were detected on day 7 postchallenge compared with day -2 prechallenge. CLINICAL RELEVANCE: Intranasal booster vaccination of beef steers at 6 months of age reduced clinical disease early after viral challenge. Weaning, transport, and viral infection promoted increased detection rates of M haemolytica and P multocida regardless of vaccination status.

Immunity Rates of Live Viral Vaccines in Pediatric Renal Transplant Candidates: A Single-Center Experience.

OBJECTIVES: Solid-organ transplant recipients are at an increased risk of severe infections due to their immunosuppressed state. Despite the recommendation of routine screening and vaccination before transplant to mitigate this danger, vaccination rates in these patients are still below desirable levels. We aimed to investigate the prevalence of positive antibody rates for measles, mumps, rubella, and varicella among children who are candidates for renal transplant. MATERIALS AND METHODS: This retrospective study was conducted at a single center and included 144 pediatric kidney transplant patients for the past 7 years. We reviewed the medical records of all participants to evaluate their serologic status for measles, mumps, rubella, and varicella viruses before kidney transplant. RESULTS: In this study, 144 pediatric kidney transplant candidates (mean age 11.5 years, 56.9% male) were enrolled, and the most frequent causes of the chronic renal disease were congenital anomalies of the kidney and urinary tract and glomerular diseases (32.6%). Seropositivity rates for measles, mumps, rubella, and varicella were 59.0%, 31.9%, 46.5%, and 43.6%, respectively, and all patients who tested negative for antibodies were vaccinated before transplant. Younger age at transplant (OR = 0.909, 95% CI = 0.840-0.923; P = .017) and congenital anomalies of the kidney and urinary tract (OR = 3.46, 95% CI = 1.1548-7.735; P = .002) were significantly associated with increased measles seropositivity, although no significant associations were observed for the other viruses. CONCLUSIONS: We observed lower seropositivity rates for measles, mumps, rubella, and varicella in pediatric kidney transplant patients versus healthy children and other previous studies. It is essential to address these suboptimal rates to protect the health of these vulnerable patients. Future research should focus on targeted interventions to improve vaccination rates and outcomes in this population.