Virus Challenge Research Articles

Immunogenicity of inactivated H5 avian influenza vaccine used in commercial laying pullet in Tehran province

Highly pathogenic avian influenza (HPAI) is a viral disease caused by some H5 and H7 subtypes of influenza virus type A in most species of birds, especially poultry. HPAI viruses are amongst the most challenging viruses that threaten both human and animal health. Consequently, various strategies such as the use of vaccines have been proposed to control the disease. After a catastrophic pandemic and the failure of conventional methods (elimination and extermination) in Iran, multiple vaccines has been used to control the disease. This study investigates the immunogenicity of two recombinant inactivated commercial vaccines of H5N1 and H5N3 subtypes in laying pullet flocks in Tehran Province, Iran. From 32 halls in 6 breeding units of laying pullets, 3200 sera and 800 tracheal and cloacal swabs were collected. After collecting the samples, Serum neutralisation (SN) and hemagglutination inhibition (HI) tests were conducted on sera to determine the serum titers of H5 specific antibody obtained from vaccine inoculation in three steps: before, after first vaccination and after the second vaccination (booster). SN and HI tests were carried out by the alpha and beta methods on the pooled samples by the vaccine type (as antigen for HI and SN), and the results were compared. The PCR was performed on the tracheal and cloacal swab samples to possibly detect the HA (H5)virus in the studied flocks. The HI test results showed that both vaccines had a Serum antibody titre above 5 (log2) after two vaccination rounds, indicating a desirable immunogenic response. The SN test results also showed a neutralisation index above 104.5 for both vaccines, indicating more than 50% reduction in antigenicity of the virus. The PCR results were negative. This study was the first investigation of immunogenicity following two-time vaccination against H5 subtype vaccines in Iranian poultry flocks, indicated suitable antibody titer against the influenza virus in vaccinated flocks.

Recombinant parainfluenza virus 5 expressing clade 2.3.4.4b H5 hemagglutinin protein confers broad protection against H5Ny influenza viruses.

The global circulation of clade 2.3.4.4b H5Ny highly pathogenic avian influenza viruses (HPAIVs) in poultry and wild birds, increasing mammal infections, continues to pose a public health threat and may even form a pandemic. An efficacious vaccine against H5Ny HPAIVs is crucial for emergency use and pandemic preparedness. In this study, we developed a parainfluenza virus 5 (PIV5)-based vaccine candidate expressing hemagglutinin (HA) protein of clade 2.3.4.4b H5 HPAIV, termed rPIV5-H5, and evaluated its safety and efficacy in mice and ferrets. Our results demonstrated that intranasal immunization with a single dose of rPIV5-H5 could stimulate H5-specific antibody responses, moreover, a prime-boost regimen using rPIV5-H5 stimulated robust humoral, cellular, and mucosal immune responses in mice. Challenge study showed that rPIV5-H5 prime-boost regimen provided sterile immunity against lethal clade 2.3.4.4b H5N1 virus infection in mice and ferrets. Notably, rPIV5-H5 prime-boost regimen provided protection in mice against challenge with lethal doses of heterologous clades 2.2, 2.3.2, and 2.3.4 H5N1, and clade 2.3.4.4h H5N6 viruses. These results revealed that rPIV5-H5 can elicit protective immunity against a diverse clade of highly pathogenic H5Ny virus infection in mammals, highlighting the potential of rPIV5-H5 as a pan-H5 influenza vaccine candidate for emergency use.IMPORTANCEClade 2.3.4.4b H5Ny highly pathogenic avian influenza viruses (HPAIVs) have been widely circulating in wild birds and domestic poultry all over the world, leading to infections in mammals, including humans. Here, we developed a recombinant PIV5-vectored vaccine candidate expressing the HA protein of clade 2.3.4.4b H5 virus. Intranasal immunization with rPIV5-H5 in mice induced airway mucosal IgA responses, high levels of antibodies, and robust T-cell responses. Importantly, rPIV5-H5 conferred complete protection in mice and ferrets against clade 2.3.4.4b H5N1 virus challenge, the protective immunity was extended against heterologous H5Ny viruses. Taken together, our data demonstrate that rPIV5-H5 is a promising vaccine candidate against diverse H5Ny influenza viruses in mammals.

An intranasal live-attenuated SARS-CoV-2 vaccine limits virus transmission

The development of effective SARS-CoV-2 vaccines has been essential to control COVID-19, but significant challenges remain. One problem is intramuscular administration, which does not induce robust mucosal immune responses in the upper airways—the primary site of infection and virus shedding. Here we compare the efficacy of a mucosal, replication-competent yet fully attenuated virus vaccine, sCPD9-ΔFCS, and the monovalent mRNA vaccine BNT162b2 in preventing transmission of SARS-CoV-2 variants B.1 and Omicron BA.5 in two scenarios. Firstly, we assessed the protective efficacy of the vaccines by exposing vaccinated male Syrian hamsters to infected counterparts. Secondly, we evaluated transmission of the challenge virus from vaccinated and subsequently challenged male hamsters to naïve contacts. Our findings demonstrate that the live-attenuated vaccine (LAV) sCPD9-ΔFCS significantly outperformed the mRNA vaccine in preventing virus transmission in both scenarios. Our results provide evidence for the advantages of locally administered LAVs over intramuscularly administered mRNA vaccines in preventing infection and reducing virus transmission.

TV005 dengue vaccine protects against dengue serotypes 2 and 3 in two controlled human infection studies.

BACKGROUNDDisease due to dengue viruses is a growing global health threat, causing 100-400 million cases annually. An ideal dengue vaccine should demonstrate durable protection against all 4 serotypes in phase III efficacy trials, however the lack of circulating serotypes may lead to incomplete efficacy data. Controlled human infection models help downselect vaccine candidates and supply critical data to supplement efficacy trials. We evaluated the efficacy of a leading live-attenuated tetravalent dengue vaccine candidate, TV005, against infection with a newly established dengue serotype 3 or an established serotype 2 challenge virus.METHODSTwo randomized, controlled clinical trials were performed. In study 1, a total of 42 participants received TV005 or placebo (n = 21 each), and 6 months later, all were challenged with dengue 2 virus (rDEN2Δ30) at a dose of 103 PFU. In study 2, a total of 23 participants received TV005 and 20 received placebo, and 6 months later, all were challenged with 104 PFU dengue 3 virus (rDEN3Δ30). The study participants were closely monitored for safety, viremia, and immunologic responses. Infection, measured by post-challenge viremia, and the occurrence of rash and neutropenia were the primary endpoints. Secondary endpoints included safety, immunologic, and virologic profiles following vaccination with TV005 and subsequent challenge with the rDEN2Δ30 or rDEN3Δ30 strain.RESULTSTV005 was well tolerated and protected all vaccinated volunteers from viremia with DENV2 or DENV3 (none infected in either group). Placebo recipients had post-challenge viremia (100% in study 1, 85% in study 2), and all experienced rash following challenge with either serotype.CONCLUSIONSTV005 is a leading tetravalent dengue vaccine candidate that fully protected against infection with DENV2 and DENV3 in an established controlled human infection model.TRIAL REGISTRATIONClinicalTrials.gov NCT02317900 and NCT02873260.FUNDINGIntramural Research Program, NIH (contract HHSN272200900010C).

Human Nasal Epithelium Organoids for Assessing Neutralizing Antibodies to a Protective SARS-CoV-2 Virus-like Particle Vaccine

Existing mRNA COVID-19 vaccines have shown efficacy in reducing severe cases and fatalities. However, their effectiveness against infection caused by emerging SARS-CoV-2 variants has waned considerably, necessitating the development of variant vaccines. Ideally, next-generation vaccines will be capable of eliciting broader and more sustained immune responses to effectively counteract new variants. Additionally, in vitro assays that more closely represent virus neutralization in humans would greatly assist in the analysis of protective vaccine-induced antibody responses. Here, we present findings from a SARS-CoV-2 VLP vaccine encompassing three key structural proteins: Spike (S), Envelope (E), and Membrane (M). The VLP vaccine effectively produced neutralizing antibodies as determined by surrogate virus neutralization test, and induced virus-specific T-cell responses: predominantly CD4+, although CD8+ T cell responses were detected. T cell responses were more prominent with vaccine delivered with AddaVax compared to vaccine alone. The adjuvanted vaccine was completely protective against live virus challenge in mice. Furthermore, we utilized air–liquid-interface (ALI)-differentiated human nasal epithelium (HNE) as an in vitro system, which authentically models human SARS-CoV-2 infection and neutralization. We show that immune sera from VLP-vaccinated mice completely neutralized SARS-CoV-2 virus infection, demonstrating the potential of ALI-HNE to assess vaccine induced Nab.

Controlled human infection study underpins efficacy of the tetravalent live-attenuated dengue vaccine TV005.

Dengue fever, caused by four distinct serotypes of the dengue virus (DENV1-4), poses a public health concern for much of the world. The NIH's Laboratory of Infectious Diseases at the National Institute of Allergy and Infectious Diseases (NIAID) has developed a series of single-dose, live-attenuated tetravalent DENV vaccines, including TV005. However, phase III trials require a lengthy three-to-five year follow-up. In contrast, controlled human infection models (CHIMs) offer a faster means to assess vaccine efficacy for any of the four serotypes. In this issue of the JCI, Pierce, Durbin, and colleagues conducted a CHIM study with attenuated DENV2 and DENV3 challenge viruses in individuals six months after vaccination with TV005. The TV005 vaccine was well tolerated and effectively protected all vaccinated individuals from viremia and rash during challenges with DENV2 or DENV3. Notably, vaccine recipients also showed serotype-specific efficacy. While long-term studies are still needed, these findings represent an important step in providing protection against dengue virus.

Comparison of HVT-ND recombinant and convection-based Newcastle disease vaccination programs in the protection against the genotype VII NDV challenges: an experimental study.

Newcastle disease virus (NDV) belongs to the Avulavirus genus and Paramyxoviridae family virus that causes acute, highly infectious Newcastle disease in poultry. The two proteins of haemagglutinin neuraminidase (HN) and fusion (F) are key virulence factors with an important role in its immunogenicity. Genotype VII NDV is still amongthe most serious viral hazards to the poultry industry worldwide. In this study, a commercial vector vaccine (HVT-NDV) was evaluated compared to the conventional vaccination strategy against Iranian genotype VII. This experiment showed that the group receiving the conventional vaccination strategy had higher antibodies, fewer clinical signs, and lower viral loads in tracheal swabs and feces. Also, two vaccine groups showed significant difference, which could have resulted from two extra vaccine doses in the conventional group. However, except for antibody levels in commercial chickens in the Iran new-generation vaccine, this difference was minor. Further, both groups showed 100% protection in the challenge study. Despite the phylogenetic gap between the NDV-F gene placed in the vector vaccine and the challenge virus (genotypes I and VII, respectively), the rHVT-NDV vaccine offered strong clinical protection and decreased challenge virus shedding considerably.

Immunogenic and Protective Properties of Recombinant Hemagglutinin of Influenza A (H5N8) Virus.

In this study, we characterized recombinant hemagglutinin (HA) of influenza A (H5N8) virus produced in Chinese hamster ovary cells (CHO-K1s). Immunochemical analysis showed that the recombinant hemagglutinin was recognized by the serum of ferrets infected with influenza A (H5N8) virus, indicating that its antigenic properties were retained. Two groups of Balb/c mice were immunized with intramuscular injection of recombinant hemagglutinin or propiolactone inactivated A/Astrakhan/3212/2020 (H5N8) influenza virus. The results demonstrated that both immunogens induced a specific antibody response as determined by ELISA. Virus neutralization assay revealed that sera of immunized animals were able to neutralize A/turkey/Stavropol/320-01/2020 (H5N8) influenza virus-the average neutralizing titer was 2560. Immunization with both recombinant HA/H5 hemagglutinin and inactivated virus gave 100% protection against lethal H5N8 virus challenge. This study shows that recombinant HA (H5N8) protein may be a useful antigen candidate for developing subunit vaccines against influenza A (H5N8) virus with suitable immunogenicity and protective efficacy.

The spike protein of the apathogenic Beaudette strain of avian coronavirus can elicit a protective immune response against a virulent M41 challenge.

The avian Gammacoronavirus infectious bronchitis virus (IBV) causes major economic losses in the poultry industry as the aetiological agent of infectious bronchitis, a highly contagious respiratory disease in chickens. IBV causes major economic losses to poultry industries across the globe and is a concern for global food security. IBV vaccines are currently produced by serial passage, typically 80 to 100 times in chicken embryonated eggs (CEE) to achieve attenuation by unknown molecular mechanisms. Vaccines produced in this manner present a risk of reversion as often few consensus level changes are acquired. The process of serial passage is cumbersome, time consuming, solely dependent on the supply of CEE and does not allow for rapid vaccine development in response to newly emerging IBV strains. Both alternative rational attenuation and cell culture-based propagation methods would therefore be highly beneficial. The majority of IBV strains are however unable to be propagated in cell culture proving a significant barrier to the development of cell-based vaccines. In this study we demonstrate the incorporation of a heterologous Spike (S) gene derived from the apathogenic Beaudette strain of IBV into a pathogenic M41 genomic backbone generated a recombinant IBV denoted M41K-Beau(S) that exhibits Beaudette's unique ability to replicate in Vero cells, a cell line licenced for vaccine production. The rIBV M41K-Beau(S) additionally exhibited an attenuated in vivo phenotype which was not the consequence of the presence of a large heterologous gene demonstrating that the Beaudette S not only offers a method for virus propagation in cell culture but also a mechanism for rational attenuation. Although historical research suggested that Beaudette, and by extension the Beaudette S protein was poorly immunogenic, vaccination of chickens with M41K-Beau(S) induced a complete cross protective immune response in terms of clinical disease and tracheal ciliary activity against challenge with a virulent IBV, M41-CK, belonging to the same serogroup as Beaudette. This implies that the amino acid sequence differences between the Beaudette and M41 S proteins have not distorted important protective epitopes. The Beaudette S protein therefore offers a significant avenue for vaccine development, with the advantage of a propagation platform less reliant on CEE.

Multivalent Epigraph Hemagglutinin Vaccine Protects against Influenza B Virus in Mice.

Influenza B virus is a respiratory pathogen that contributes to seasonal epidemics, accounts for approximately 25% of global influenza infections, and can induce severe disease in young children. While vaccination is the most commonly used method of preventing influenza infections, current vaccines only induce strain-specific responses and have suboptimal efficacy when mismatched from circulating strains. Further, two influenza B virus lineages have been described, B/Yamagata-like and B/Victoria-like, and the limited cross-reactivity between the two lineages provides an additional barrier in developing a universal influenza B virus vaccine. Here, we report a novel multivalent vaccine using computationally designed Epigraph hemagglutinin proteins targeting both the B/Yamagata-like and B/Victoria-like lineages. When compared to the quadrivalent commercial vaccine, the Epigraph vaccine demonstrated increased breadth of neutralizing antibody and T cell responses. After lethal heterologous influenza B virus challenge, mice immunized with the Epigraph vaccine were completely protected against both weight loss and mortality. The superior cross-reactive immunity conferred by the Epigraph vaccine immunogens supports their continued investigation as a universal influenza B virus vaccine.

An Expeditious Neutralization Assay for Porcine Reproductive and Respiratory Syndrome Virus Based on a Recombinant Virus Expressing Green Fluorescent Protein.

Due to the extensive genetic and antigenic variation in Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), as well as its rapid mutability and evolution, PRRS prevention and control can be challenging. An expeditious and sensitive neutralization assay for PRRSV is presented to monitor neutralizing antibodies (NAbs) in serum during vaccine research. Here, a PRRSV expressing eGFP was successfully rescued with reverse genetics based on the infectious clone HuN4-F112-eGFP which we constructed. The fluorescent protein expressions of the reporter viruses remained stable for at least five passages. Based on this reporter virus, the neutralization assay can be easily used to evaluate the level of NAbs by counting cells with green fluorescence. Compared with the classical CPE assay, the newly developed assay increases sensitivity by one- to four-fold at the early antibody response stage, thus saving 2 days of assay waiting time. By using this assay to unveil the dynamics of neutralizing antibodies against PRRSV, priming immunity through either a single virulent challenge or only vaccination could produce limited NAbs, but re-infection with PRRSV would induce a faster and stronger NAb response. Overall, the novel HuN4-F112-eGFP-based neutralization assay holds the potential to provide a highly efficient platform for evaluating the next generation of PRRS vaccines.

The Chinese Hamster Ovary Cell-Based H9 HA Subunit Avian Influenza Vaccine Provides Complete Protection against the H9N2 Virus Challenge in Chickens.

(1) Background: Avian influenza has attracted widespread attention because of its severe effect on the poultry industry and potential threat to human health. The H9N2 subtype of avian influenza viruses was the most prevalent in chickens, and there are several commercial vaccines available for the prevention of the H9N2 subtype of avian influenza viruses. However, due to the prompt antigenic drift and antigenic shift of influenza viruses, outbreaks of H9N2 viruses still continuously occur, so surveillance and vaccine updates for H9N2 subtype avian influenza viruses are particularly important. (2) Methods: In this study, we constructed a stable Chinese hamster ovary cell line (CHO) to express the H9 hemagglutinin (HA) protein of the major prevalent H9N2 strain A/chicken/Daye/DY0602/2017 with genetic engineering technology, and then a subunit H9 avian influenza vaccine was prepared using the purified HA protein with a water-in-oil adjuvant. (3) Results: The results showed that the HI antibodies significantly increased after vaccination with the H9 subunit vaccine in specific-pathogen-free (SPF) chickens with a dose-dependent potency of the immunized HA protein, and the 50 μg or more per dose HA protein could provide complete protection against the H9N2 virus challenge. (4) Conclusions: These results indicate that the CHO expression system could be a platform used to develop the subunit vaccine against H9 influenza viruses in chickens.

Enhanced immunogenicity and protective efficacy in mice following a Zika DNA vaccine designed by modulation of membrane-anchoring regions and its association to adjuvants.

Zika virus (ZIKV) is a re-emerging pathogen with high morbidity associated to congenital infection. Despite the scientific advances since the last outbreak in the Americas, there are no approved specific treatment or vaccines. As the development of an effective prophylactic approach remains unaddressed, DNA vaccines surge as a powerful and attractive candidate due to the efficacy of sequence optimization in achieving strong immune response. In this study, we developed four DNA vaccine constructs encoding the ZIKV prM/M (pre-membrane/membrane) and E (envelope) proteins in conjunction with molecular adjuvants. The DNA vaccine candidate (called ZK_ΔSTP), where the entire membrane-anchoring regions were completely removed, was far more immunogenic compared to their counterparts. Furthermore, inclusion of the tPA-SP leader sequence led to high expression and secretion of the target vaccine antigens, therefore contributing to adequate B cell stimulation. The ZK_ΔSTP vaccine induced high cellular and humoral response in C57BL/6 adult mice, which included high neutralizing antibody titers and the generation of germinal center B cells. Administration of ZK-ΔSTP incorporating aluminum hydroxide (Alum) adjuvant led to sustained neutralizing response. In consistency with the high and long-term protective response, ZK_ΔSTP+Alum protected adult mice upon viral challenge. Collectively, the ZK_ΔSTP+Alum vaccine formulation advances the understanding of the requirements for a successful and protective vaccine against flaviviruses and is worthy of further translational studies.

PEDV-spike-protein-expressing mRNA vaccine protects piglets against PEDV challenge.

Porcine epidemic diarrhea virus (PEDV), a swine enteropathogenic coronavirus, causes severe diarrhea in neonatal piglets, which is associated with a high mortality rate. Thus, developing effective and safe vaccines remains a top priority for controlling PEDV infection. Here, we designed two lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) vaccines encoding either the full-length PEDV spike (S) protein or a multiepitope chimeric spike (Sm) protein. We found that the S mRNA-LNP vaccine was superior to the Sm mRNA-LNP vaccine at inducing antibody and cellular immune responses in mice. Evaluation of the immunogenicity and efficacy of the S mRNA vaccine in piglets confirmed that it induced robust PEDV-specific humoral and cellular immune responses in vivo. Importantly, the S mRNA-LNP vaccine not only protected actively immunized piglets against PEDV but also equipped neonatal piglets with effective passive anti-PEDV immunity in the form of colostrum-derived antibodies after the immunization of sows. Our findings suggest that the PEDV-S mRNA-LNP vaccine is a promising candidate for combating PEDV infection.IMPORTANCEPorcine epidemic diarrhea virus (PEDV) continues to harm the global swine industry. It is important to develop a highly effective vaccine to control PEDV infection. Here, we report a PEDV spike (S) mRNA vaccine that primes a potent antibody response and antigen-specific T-cell responses in immunized piglets. Active and passive immunization can protect piglets against PED following the virus challenge. This study highlights the efficiency of the PEDV-S mRNA vaccine and represents a viable approach for developing an efficient PEDV vaccine.

Karyotypic stasis and swarming influenced the evolution of viral tolerance in a species-rich bat radiation

The emergence of COVID-19 and severe acute respiratory syndrome (SARS) has prioritized understanding bats' viral tolerance. Myotis bats are exceptionally species rich and have evolved viral tolerance. They also exhibit swarming, a cryptic behavior where large, multi-species assemblages gather for mating, which has been hypothesized to promote interspecific hybridization. To resolve the coevolution of genome architecture and their unusual antiviral tolerance, we undertook a phylogenomic analysis of 60 Old World Myotis genomes. We demonstrate an extensive history of introgressive hybridization that has replaced the species phylogeny across 17%-93% of the genome except for pericentromeric regions of macrochromosomes. Introgression tracts were enriched on microchromosome regions containing key antiviral pathway genes overexpressed during viral challenge experiments. Together, these results suggest that the unusual Myotis karyotype may have evolved to selectively position immune-related genes in high recombining genomic regions prone to introgression of divergent alleles, including a diversity of interleukin loci responsible for the release of pro-inflammatory cytokines.

Fusion peptide-directed antibodies: Humoral armor against HIV-1 infection.

Infused neutralizing antibodies to the fusion peptide of the HIV envelope glycoprotein protected macaques from mucosal viral challenge (Pegu et al.).

Immunogenicity and protective efficacy of a trimeric full-length S protein subunit vaccine for porcine epidemic diarrhea virus

Porcine epidemic diarrhea virus (PEDV) has caused serious economic losses to the pig husbandry worldwide, and the effects of existing commercialized vaccines are suboptimal. Therefore, research to develop an efficacious vaccine for prevention and control of PEDV is essential. In this study, we designed and produced trimerized proteins of full-length PEDV spike (S) protein, S1 subunit, and a tandem of multiple epitopes of S protein using an efficient mammalian expression vector system in HEK 293F cells. The immunogenicity of two commercial adjuvants, M401 and M103, was also evaluated in mice. Enzyme-linked immunosorbent assays demonstrated that all immunized mice generated highly systemic PEDV S-specific IgG and IgA antibodies. Mice in S/M103-immunized group generated the highest neutralizing antibody titer with 1:96. Compared with control group, the subunit vaccines elicited multifunctional CD3+CD4+ and CD3+CD8+ T cells, B220+CD19+ B cells, and CD3-CD49b+ natural killer cells in the spleen. PEDV S/M103 vaccine, which had the best immune effect, was selected for further evaluation in piglets. Immunization with S/M103 vaccine induced high levels of S-specific IgG, IgA, and neutralizing antibodies, and increased the proliferation of peripheral blood mononuclear cells and the expression levels of interferon-γ and interleukin-4 in peripheral blood of piglets. Virus challenge test results showed significantly lower diarrheal index scores and fecal viral loads, and less pathological damage to the intestines in S/M103-immunized piglets than in controls, indicating that S/M103 provides good protection against the virulent virus challenge. Our findings suggest that trimeric PEDV S/M103 has potential as a clinical vaccine candidate.

A Mixture of T-Cell Epitope Peptides Derived from Human Respiratory Syncytial Virus F Protein Conferred Protection in DR1-TCR Tg Mice.

Human respiratory syncytial virus (HRSV) poses a significant disease burden on global health. To date, two vaccines that primarily induce humoral immunity to prevent HRSV infection have been approved, whereas vaccines that primarily induce T-cell immunity have not yet been well-represented. To address this gap, 25 predicted T-cell epitope peptides derived from the HRSV fusion protein with high human leukocyte antigen (HLA) binding potential were synthesized, and their ability to be recognized by PBMC from previously infected HRSV cases was assessed using an ELISpot assay. Finally, nine T-cell epitope peptides were selected, each of which was recognized by at least 20% of different donors' PBMC as potential vaccine candidates to prevent HRSV infection. The protective efficacy of F-9PV, a combination of nine peptides along with CpG-ODN and aluminum phosphate (Al) adjuvants, was validated in both HLA-humanized mice (DR1-TCR transgenic mice, Tg mice) and wild-type (WT) mice. The results show that F-9PV significantly enhanced protection against viral challenge as evidenced by reductions in viral load and pathological lesions in mice lungs. In addition, F-9PV elicits robust Th1-biased response, thereby mitigating the potential safety risk of Th2-induced respiratory disease during HRSV infection. Compared to WT mice, the F-9PV mice exhibited superior protection and immunogenicity in Tg mice, underscoring the specificity for human HLA. Overall, our results demonstrate that T-cell epitope peptides provide protection against HRSV infection in animal models even in the absence of neutralizing antibodies, indicating the feasibility of developing an HRSV T-cell epitope peptide-based vaccine.

An HTLV-1 envelope mRNA vaccine is immunogenic and protective in New Zealand rabbits.

Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus responsible for adult T-cell leukemia/lymphoma, a severe and fatal CD4+ T-cell malignancy. Additionally, HTLV-1 can lead to a chronic progressive neurodegenerative disease known as HTLV-1-associated myelopathy/tropical spastic paraparesis. Unfortunately, the prognosis for HTLV-1-related diseases is generally poor, and effective treatment options are limited. In this study, we designed and synthesized a codon optimized HTLV-1 envelope (Env) mRNA encapsulated in a lipid nanoparticle (LNP) and evaluated its efficacy as a vaccine candidate in an established rabbit model of HTLV-1 infection and persistence. Immunization regimens included a prime/boost protocol using Env mRNA-LNP or control green fluorescent protein (GFP) mRNA-LNP. After immunization, rabbits were challenged by intravenous injection with irradiated HTLV-1 producing cells. Three rabbits were partially protected and three rabbits were completely protected against HTLV-1 challenge. These rabbits were then rechallenged 15 weeks later, and two rabbits maintained sterilizing immunity. In Env mRNA-LNP immunized rabbits, proviral load and viral gene expression were significantly lower. After viral challenge in the Env mRNA-LNP vaccinated rabbits, an increase in both CD4+/IFN-γ+ and CD8+/IFN-γ+ T-cells was detected when stimulating with overlapping Env peptides. Env mRNA-LNP elicited a detectable anti-Env antibody response after prime/boost vaccination in all animals and significantly higher levels of neutralizing antibody activity. Neutralizing antibody activity was correlated with a reduction in proviral load. These findings hold promise for the development of preventive strategies and therapeutic interventions against HTLV-1 infection and its associated diseases.IMPORTANCEmRNA vaccine technology has proven to be a viable approach for effectively triggering immune responses that protect against or limit viral infections and disease. In our study, we synthesized a codon optimized human T-cell leukemia virus type 1 (HTLV-1) envelope (Env) mRNA that can be delivered in a lipid nanoparticle (LNP) vaccine approach. The HTLV-1 Env mRNA-LNP produced protective immune responses against viral challenge in a preclinical rabbit model. HTLV-1 is primarily transmitted through direct cell-to-cell contact, and the protection offered by mRNA vaccines in our rabbit model could have significant implications for optimizing the development of other viral vaccine candidates. This is particularly important in addressing the challenge of enhancing protection against infections that rely on cell-to-cell transmission.

Evaluation of a Vaccine Candidate Designed for Broad-Spectrum Protection against Type A Foot-and-Mouth Disease in Asia.

Foot-and-mouth disease (FMD) vaccines are currently the most powerful protective and preventive measures used to control FMD. In this study, the chimeric vaccine strain containing antigenic epitopes from the FMD virus serotype A, which belongs to the ASIA topotype, was produced and evaluated. The chimeric vaccine strains contain sea-97/G1 (VP4, VP2, VP3) and A22 Iraq (VP1) or G-VII (VP1) for use in FMD vaccines in Asia. The 50% protective dose was determined in mice. Vaccinated mice were challenged with three different type A viruses (Sea-97/G1, Sea-97/G2, G-VII clade) seven days post-vaccination (dpv), and mice that received the vaccine candidates were protected against the three viruses. The protective capability of one of the vaccine candidates was evaluated in pigs. Vaccinated pigs were challenged with three different type A viruses (Sea-97/G1, Sea-97/G2, G-VII clade) at 28 dpv, and pigs that received the vaccine candidate were protected against the three viruses. The results showed that this vaccine candidate, which was designed to provide protection against FMD in Asia, efficiently protected pigs against virus challenge and thus has potential as a broad-spectrum vaccine for various epidemic FMD viruses.