The combination of infectious bronchitis virus BR1 and Mass vaccines provides broad protection.

Two vaccination-challenge trials were performed using a commercial infectious bronchitis virus (IBV) BR1 vaccine, given alone or combined with a commercial IBV Mass vaccine against challenges with IBV M41, 793B, D388 (QX), Q1, Brasil-1 or Variant 2 challenge viruses, which includes the IB viruses that are dominant in South America. The efficacy of the vaccines against the challenge viruses was investigated by determination of the ciliary activity of the tracheal epithelium after challenge. The level of protection induced by the IBV BR1 vaccine alone against the six IBV challenge strains, of which five were of heterologous genotypes, varied from 50% to 100% with an average of 80%. The level of protection induced by the combination of the IBV BR1 and IBV Mass vaccines against the six IBV challenge strains, of which four were of heterologous genotypes, varied from 80% to 100% with an average of 92%. Vaccination with IBV BR1 alone provided a high level of protection against most tested challenge viruses, though the combination of IBV BR1 and IBV Mass was more consistent, showing less variation and compliance with the criterium mentioned in the European Pharmacopoeia 10th edition (at least 80% protection) for all tested challenge viruses. These trials show that vaccination with a combination of IBV BR1 and IBV Mass vaccines provides high levels of protection against the circulating IBV strains in South America.

A chimeric strain of porcine reproductive and respiratory syndrome virus 2 derived from HP-PRRSV and NADC30-like PRRSV confers cross-protection against both strains.

Porcine reproductive and respiratory syndrome (PRRS) is one of the most significant swine viral infectious diseases worldwide. Vaccination is a key strategy for the control and prevention of PRRS. At present, the NADC30-like PRRSV strain has become the predominant epidemic strain in China, superseding the HP-PRRSV strain. The existing commercial vaccines offer substantial protection against HP-PRRSV, but their efficacy against NADC30-like PRRSV is limited. The development of a novel vaccine that can provide valuable cross-protection against both NADC30-like PRRSV and HP-PRRSV is highly important. In this study, an infectious clone of a commercial MLV vaccine strain, GD (HP-PRRSV), was first generated (named rGD). A recombinant chimeric PRRSV strain, rGD-SX-5U2, was subsequently constructed by using rGD as a backbone and embedding several dominant immune genes, including the NSP2, ORF5, ORF6, and ORF7 genes, from an NADC30-like PRRSV isolate. In vitro experiments demonstrated that chimeric PRRSV rGD-SX-5U2 exhibited high tropism for MARC-145 cells, which is of paramount importance in the production of PRRSV vaccines. Moreover, subsequent in vivo inoculation and challenge experiments demonstrated that rGD-SX-5U2 confers cross-protection against both HP-PRRSV and NADC30-like PRRSV, including an improvement in ADG levels and a reduction in viremia and lung tissue lesions. In conclusion, our research demonstrated that the chimeric PRRSV strain rGD-SX-5U2 is a novel approach that can provide broad-spectrum protection against both HP-PRRSV and NADC30-like PRRSV. This may be a significant improvement over previous MLV vaccinations.

An asymptomatic geminivirus activates autophagy and enhances plant defenses against diverse pathogens.

Plant viral diseases cause great losses in agricultural production. Virus cross-protection is a strategy in which a mild virus is employed to shield plants against subsequent infections by severe viral strains. However, this approach is restricted to protection against the same viruses. In this study, we observed that pre-inoculation with apple geminivirus (AGV) reduced the accumulation of secondarily infected heterologous viruses, such as cucumber mosaic virus, potato virus X, and tobacco mosaic virus in Nicotiana benthamiana, tomato, and pepper plants. Transcriptional expression analysis showed that autophagy-related genes were transcriptionally up-regulated upon AGV inoculation at an early stage of infection. Accordingly, autophagic activity was observed to be elevated following AGV infection. Interestingly, AGV accumulation was reduced in autophagy-deficient plants, suggesting that autophagy activation promotes AGV infection in the plant. Moreover, pre-inoculation with AGV provided cross-protection against infection with a phytopathogenic bacterium (Pseudomonas syringae) and fungus (Botrytis cinerea) in Nicotiana species. In summary, our study showed that AGV, an asymptomatic virus, could protect plants against severe viral, fungal, and bacterial diseases to some extent through the activation of autophagy pathways, highlighting its potential as a biocontrol agent for managing a wide range of plant crop diseases in the field.

Expression of stress responsive genes enables Limosilactobacillus reuteri to cross-protection against acid, bile salt, and freeze-drying.

Introduction: Limosilactobacillus reuteri effectively colonizing the gut, secretes antimicrobial compounds and strengthens immune system function. Considering these health benefits, increasing its stress assessments efficiency could improve its commercial viability. Methods: In this work, the resistance of L. reuteri FP41 to acid, bile salts, and freeze-drying was examined. Results: The findings showed that strain FP41 demonstrated a strong resistance to acid/bile salt stresses. The transcriptome revealed a significant up-regulation of various stress response genes, including those related to membrane integrity, glutamine metabolism, OsmC family protein, ABC transporters, and chaperonin. Subsequent research demonstrated that overexpression of three stress response-specific proteins, including glutamate decarboxylase GatD, osmotically induced bacterial protein OsmC, and membrane protein component CsbD, significantly increased the survival rate of L. reuteri Z204 under acid/bile salts stress. Notably, overexpression of the OsmC, CsbD, and GatD proteins also enhanced the survival of L. reuteri after freeze-drying. Discussion: The development of a unique cross-protection method is highlighted in this study, that might significantly increase cellular resistance to acid, bile salts, and cold stresses. This finding could significantly impact the way that L. reuteri is employed in industrial manufacturing processes.

Protection against Mycoplasma hyorhinis infection in commercial pigs via immunization with inactivated vaccines prepared with homologous or heterologous strains.

Mycoplasma hyorhinis is a highly prevalent pathogen in pig farms worldwide, causing polyserositis and polyarthritis, resulting in great economic losses. Previous genotyping and pathogenic studies have revealed significant genetic and antigenic diversity among M. hyorhinis strains. While there are reports on M. hyorhinis vaccine development, the cross-protection between different M. hyorhinis strains has not been clarified. In this study, two M. hyorhinis strains (HEF-16 and JS-54), belonging to different sequence types, were inactivated to produce vaccines. Pigs were vaccinated respectively and subsequently infected with strain HEF-16. The protection against challenge with homologous or heterologous strains was determined and compared. Both vaccinated groups of pigs exhibited a high antibody titer two weeks after the first vaccination, and significant decreases in pathogen load in joints, along with an increase in average daily weight gain compared to the challenged group after M. hyorhinis challenge. Pigs immunized with the HEF-16-derived vaccine showed a significant reduction in joint swelling and lameness, similar to pigs immunized with the JS-54-derived vaccine. At necropsy, animals in the challenged group exhibited moderate-to-severe polyserositis and arthritis, whereas pathological changes were greatly reduced in animals from the vaccinated groups. No significant differences were observed in clinical symptoms nor pathological damages between the two vaccinated groups. Overall, our study demonstrates the effective protection of the inactivated M. hyorhinis vaccines against challenges with homologous or heterologous strains in commercial pigs. This indicates a promising clinical application prospect for inactivated bacterin vaccines in preventing M. hyorhinis-related diseases in pig farms.

Challenging boundaries: is cross-protection evaluation necessary for African swine fever vaccine development? A case of oral vaccination in wild boar.

African swine fever (ASF) poses a significant threat to domestic pigs and wild boar (Sus scrofa) populations, with the current epidemiological situation more critical than ever. The disease has spread across five continents, causing devastating losses in the swine industry. Although extensive research efforts are ongoing to develop an effective and safe vaccine, this goal remains difficult to achieve. Among the potential vaccine candidates, live attenuated viruses (LAVs) have emerged as the most promising option due to their ability to provide strong protection against experimental challenges. However, ASF virus (ASFV) is highly diverse, with genetic and phenotypic variations across different isolates, which differ in virulence. This study highlights the limitations of a natural LAV strain (Lv17/WB/Rie1), which showed partial efficacy against a highly virulent and partially heterologous isolate (Arm07; genotype II). However, the LAV's effectiveness was incomplete when tested against a more phylogenetically distant virus (Ken06.Bus; genotype IX). These findings raise concerns about the feasibility of developing a universal vaccine for ASFV in the near future, emphasizing the urgent need to assess the protective scope of LAV candidates across different ASFV isolates to better define their limitations.

Immunogenicity and Protectivity of Sputnik V Vaccine in hACE2-Transgenic Mice against Homologous and Heterologous SARS-CoV-2 Lineages Including Far-Distanced Omicron BA.5.

BACKGROUND: The SARS-CoV-2 virus continuously acquires mutations, leading to the emergence of new variants. Notably, the effectiveness of global vaccination efforts has significantly declined with the rise and spread of the B.1.1.529 (Omicron) variant. METHODS: The study used virological, immunological and histological research methods, as well as methods of working with laboratory animals. In this study, we evaluated the Gam-COVID-Vac (Sputnik V), an adenoviral vaccine developed by the N.F. Gamaleya National Research Center for Epidemiology and Microbiology, and conducted experiments on hemizygous K18-ACE2-transgenic F1 mice. The variants studied included B.1.1.1, B.1.1.7, B.1.351, B.1.1.28/P.1, B.1.617.2, and B.1.1.529 BA.5. RESULTS: Our findings demonstrate that the Sputnik V vaccine elicits a robust humoral and cellular immune response, effectively protecting vaccinated animals from challenges posed by various SARS-CoV-2 variants. However, we observed a notable reduction in vaccine efficacy against the B.1.1.529 (Omicron BA.5) variant. CONCLUSIONS: Our results indicate that ongoing monitoring of emerging mutations is crucial to assess vaccine efficacy against new SARS-CoV-2 variants to identify those with pandemic potential. If protective efficacy declines, it will be imperative to develop new vaccines tailored to current variants of the virus.

Strengthening global health resilience: Marburg virus-like particle vaccines and the One Health approach.

The Marburg virus (MARV), belonging to the Filoviridae family, poses a significant global health threat, emphasizing the urgency to develop Marburg virus-like particle (VLP) vaccines for outbreak mitigation. The virus's menacing traits accentuate the need for such vaccines, which can be addressed by VLPs that mimic its structure safely, potentially overcoming past limitations. Early Marburg vaccine endeavors and their challenges are examined in the historical perspectives section, followed by an exploration of VLPs as transformative tools, capable of eliciting immune responses without conventional risks. Noteworthy milestones and achievements in Marburg VLP vaccine development, seen through preclinical and clinical trials, indicate potential cross-protection. Ongoing challenges, encompassing durability, strain diversity, and equitable distribution, are addressed, with proposed innovations like novel adjuvant, mRNA technology, and structure-based design poised to enhance Marburg VLP vaccines. This review highlights the transformative potential of Marburg VLPs in countering the virus, showcasing global collaboration, regulatory roles, and health equity for a safer future through the harmonious interplay of science, regulation, and global efforts.

Characterization of Streptococcus agalactiae 1a isolated from farmed Nile tilapia (Oreochromis niloticus) in North America, Central America, and Southeast Asia.

Streptococcosis caused by Streptococcus agalactiae 1a in Nile tilapia (Oreochromis niloticus) is a severe disease challenge for the global supply of tilapia. Currently, the extensive use of antibiotics is the primary curative tool used to minimize the impact of the disease. Vaccination is a prophylactic measure that has been shown to reduce antibiotic use in the aquaculture sector substantially. However, no commercially licensed vaccine against Streptococcus agalactiae 1a is currently available. This study aimed to investigate, through molecular and immunological methods, if Streptococcus agalactiae 1a isolates collected from North America (NAM), Central America (CAM), and Southeast Asia (SEA) were similarly suitable for the development of a potentially effective vaccine to serve the global tilapia farming industry. Our comparative data showed that the Streptococcus agalactiae 1a isolates from NAM, CAM and SEA had similar biochemical profiles, and genetic multi-locus sequence typing (MLST) analysis showed that the NAM and CAM isolates belonged to sequence type 7 (ST-7) and clonal complex 1, while isolates from SEA grouped into three sequence types (ST-1650, ST-500, and ST-7) and two distinct clonal complexes (CC1 and CC12). Isolates from NAM, CAM, and SEA displayed similar antigenic profiles determined by western blotting with polyclonal rabbit antisera, which was supported by in vivo cross-protection studies, showing that fish immunized with vaccines based on SEA and CAM isolates with different genetic MLST profiles were highly protected against cross-challenge using the same bacterial strains for challenge. Overall, the data obtained from our investigations provide strong indications that Streptococcus agalactiae 1a distributed in NAM, CAM, and SEA are serologically uniform pathogens, and vaccines based on isolates of Streptococcus agalactiae 1a from these regions may be suited for vaccination of tilapia worldwide.

Implications of Cross-Reactivity and Cross-Protection for Pneumococcal Vaccine Development.

Pneumococcal vaccines are a cornerstone for the prevention of pneumococcal diseases, reducing morbidity and mortality in children and adults worldwide. Pneumococcal vaccine composition is based on the polysaccharide capsule of Streptococcus pneumoniae, which is one of the most important identified contributors to the pathogen's virulence. Similarities in the structural composition of polysaccharides included in licensed pneumococcal vaccines may result in cross-reactivity of immune response against closely related serotypes, including serotypes not included in the vaccine. Therefore, it is important to understand whether cross-reactive antibodies offer clinical protection against pneumococcal disease. This review explores available evidence of cross-reactivity and cross-protection associated with pneumococcal vaccines, the challenges associated with the assessment of cross-reactivity and cross-protection, and implications for vaccine design and development.

Enhancing freeze-thaw tolerance in baker's yeast: strategies and perspectives.

Frozen dough technology is important in modern bakery operations, facilitating the transportation of dough at low temperatures to downstream sales points. However, the freeze-thaw process imposes significant stress on baker's yeast, resulting in diminished viability and fermentation capacity. Understanding the mechanisms underlying freeze-thaw stress is essential for mitigating its adverse effects on yeast performance. This review delves into the intricate mechanisms underlying freeze-thaw stress, focusing specifically on Saccharomyces cerevisiae, the primary yeast used in baking, and presents a wide range of biotechnological approaches to enhance freeze-thaw resistance in S. cerevisiae. Strategies include manipulating intracellular metabolites, altering membrane composition, managing antioxidant defenses, mediating aquaporin expression, and employing adaptive evolutionary and breeding techniques. Addressing challenges and strategies associated with freeze-thaw stress, this review provides valuable insights for future research endeavors, aiming to enhance the freeze-thaw tolerance of baker's yeast and contribute to the advancement of bakery science.

Molecular approaches for the management of papaya ringspot virus infecting papaya: a comprehensive review.

Papaya ringspot virus (PRSV) is a catastrophic disease that causes huge yield losses in papaya cultivation around the world. Yield losses in severely infected plants can be upto 100%. Because of this disease, papaya cultivation has been shifted to other crops in some areas of the world. Many conventional methods and breeding approaches are used against this disease, which turns out to be less effective. Considering the yield loss caused by PRSV in papaya, it is high time to focus on alternative control methods. To implement effective management strategies, molecular approaches such as Marker Assisted Breeding (MAS) or transgenic methods involving post-transcriptional gene silencing targeting the genome viz., coat protein, replicase gene, or HC Pro can be pursued. However, the public's reluctance to widely accept the transgenic approach due to health and environmental concerns necessitates a consideration of non-transgenic alternatives. Prioritizing safety and ensuring efficient virus control, non-transgenic approaches which encompass cross-protection, genome editing, and topical applications of dsRNA to induce gene silencing within the host, can be adopted. This review aims to provide comprehensive insights of various molecular tools used in managing PRSV which in turn will help in sustainable agriculture.

Changes in Genital HPV Prevalence during 12 Years Girls-Only Bivalent HPV Vaccination: Results from a Biennial Repeated Cross-Sectional Study.

BACKGROUND: From 2009 until 2021, bivalent HPV vaccination was offered only to girls in the Netherlands. We aimed to study the impact of girls-only HPV vaccination on genital HPV prevalence among young adults. METHODS AND FINDINGS: PASSYON is a biennial repeated cross-sectional study (2009-21) among sexual health clinic clients aged 16-24 years old. Questionnaires elicited data on demographics, sexual behaviour and HPV vaccination status. Genital samples were collected and analysed using a PCR-based assay (SPF10-LiPA25). Type-specific prevalence trends of 12 high-risk (hr) genotypes were analysed as the adjusted average annual change (aAAC), estimated using Poisson GEE models. The relation between aAAC and phylogenetic distance to HPV-16/18 was assessed by means of regression and rank correlation analysis. Questionnaires and genital samples were collected from 8,889 females and 3,300 heterosexual males (HM). 4,829 females reported to be unvaccinated (54·3%). Among females (irrespective of vaccination status), prevalences of HPV-16/18/31/33/35/45 decreased significantly over time. Increasing trends were observed for HPV-39/52/56. Among both HM and unvaccinated females HPV-16/18 prevalence significantly declined, as did HPV-31 among HM. In contrast, HPV-52/58 increased significantly among HM and unvaccinated females. The type-specific aAAC correlated well with the phylogenetic distance to HPV-16/18. CONCLUSIONS: During twelve years girls-only bivalent HPV vaccination in the Netherlands, decreasing trends of the vaccine types and cross-protected types were observed among females. Herd protection of vaccine-types was observed for HM and unvaccinated females, and one cross-protected type for HM. Increasing prevalence trends of HPV types with large phylogenetic distance to the vaccine types might indicate type-replacement.

Coronavirus nucleocapsid-based vaccine provides partial protection against hetero-species coronavirus in murine models.

Most coronavirus vaccines focus on the spike (S) antigen, but the frequent mutations in S raise concerns about the vaccine efficacy against new variants. Although additional antigens with conserved sequences are have been tested, the extent to which these vaccines can provide immunity against different coronavirus species remains unclear. In this study, we assessed the potential of nucleocapsid (N) as a coronavirus vaccine antigen. Immunization with MERS-CoV N induced robust immune responses, providing significant protection against MERS-CoV. Notably, MERS-CoV N elicited cross-reactive T cell responses to SARS-CoV-2 N and significantly reduced lung inflammation following a SARS-CoV-2 challenge in the transient hACE2 mouse model. However, in K18-hACE transgenic mice, the vaccine showed limited protection. Collectively, our findings suggest that coronavirus N can be an effective vaccine antigen against homologous viruses, but its efficacy may vary across different coronaviruses, highlighting the need for further research on pan-coronavirus vaccines using conserved antigens.

The Generation of Attenuated Mutants of East Asian Passiflora Virus via Deletion and Mutation in the N-Terminal Region of the HC-Pro Gene for Control through Cross-Protection.

East Asian Passiflora virus (EAPV) causes passionfruit woodiness disease, a major threat limiting passionfruit production in eastern Asia, including Taiwan and Vietnam. In this study, an infectious cDNA clone of a Taiwanese severe isolate EAPV-TW was tagged with a green fluorescent protein (GFP) reporter to monitor the virus in plants. Nicotiana benthamiana and yellow passionfruit plants inoculated with the construct showed typical symptoms of EAPV-TW. Based on our previous studies on pathogenicity determinants of potyviral HC-Pros, a deletion of six amino acids (d6) alone and its association with a point mutation (F8I, simplified as I8) were conducted in the N-terminal region of the HC-Pro gene of EAPV-TW to generate mutants of EAPV-d6 and EAPV-d6I8, respectively. The mutant EAPV-d6I8 caused infection without conspicuous symptoms in N. benthamiana and yellow passionfruit plants, while EAPV-d6 still induced slight leaf mottling. EAPV-d6I8 was stable after six passages under greenhouse conditions and displayed a zigzag pattern of virus accumulation, typical of a beneficial protective virus. The cross-protection effectiveness of EAPV-d6I8 was evaluated in both N. benthamiana and yellow passionfruit plants under greenhouse conditions. EAPV-d6I8 conferred complete cross-protection (100%) against the wild-type EAPV-TW-GFP in both N. benthamiana and yellow passionfruit plants, as verified by no severe symptoms, no fluorescent signals, and PCR-negative status for GFP. Furthermore, EAPV-d6I8 also provided complete protection against Vietnam's severe strain EAPV-GL1 in yellow passionfruit plants. Our results indicate that the attenuated mutant EAPV-d6I8 has great potential to control EAPV in Taiwan and Vietnam via cross-protection.

How has post-implementation surveillance of high-coverage vaccination with HPV16/18-AS04 vaccine in England added to evidence about its cross-protective effects?

BACKGROUND: Bivalent human papillomavirus HPV16/18-AS04 vaccine (Cervarix, GSK) offers direct protection against HPV16/18. Results from randomised controlled trials showed cross protective effects and suggested that declines in some closely related HPV types could be expected in a population with high vaccination coverage. AIM: To evaluate the evidence for cross-protection afforded by HPV16/18-AS04 from post-implementation surveillance in England, and how this complements clinical trial data and post-implementation observations in other countries. METHODS: Evidence of cross-protection in young women offered vaccination with HPV16/18-AS04 was gathered from HPV surveillance in England. Data from clinical trials and other post-implementation studies were reviewed. RESULTS: Surveillance using anonymised residual specimens in England found declines of 52.3%, 67.4% and 33.3% against grouped HPV-31/33/45 in 16-18, 19-21, and 22-24 year olds, respectively. Additionally, type-specific analysis found that the prevalence of HPV31 declined to below 1% across all age groups. Cross-protection has been monitored and maintained for over 10 years since the introduction of the vaccination programme. Cross-protection against HPV6/11 was not found in English surveillance outcomes. CONCLUSION: Surveillance of type-specific infections in vaccine-eligible populations in England has generated clear evidence of cross-protective effects from HPV16/18-AS04 vaccination against high-risk HPV 31/33/45 infections, consistent with other post-implementation observations and confirming and in some ways exceeding expectations from clinical trials.

Disulfide-stabilized trimeric hemagglutinin ectodomains provide enhanced heterologous influenza protection.

Influenza virus infection poses a continual menace to public health. Here, we developed soluble trimeric HA ectodomain vaccines by establishing interprotomer disulfide bonds in the stem region, which effectively preserve the native antigenicity of stem epitopes. The stable trimeric H1 ectodomain proteins exhibited higher thermal stabilities in comparison with unmodified HAs and showed strong binding activities towards a panel of anti-stem cross-reactive antibodies that recognize either interprotomer or intraprotomer epitopes. Negative stain transmission electron microscopy (TEM) analysis revealed the stable trimer architecture of the interprotomer disulfide-stapled WA11#5, NC99#2, and FLD#1 proteins as well as the irregular aggregation of unmodified HA molecules. Immunizations of mice with those trimeric HA ectodomain vaccines formulated with incomplete Freund's adjuvant elicited significantly more potent cross-neutralizing antibody responses and offered broader immuno-protection against lethal infections with heterologous influenza strains compared to unmodified HA proteins. Additionally, the findings of our study indicate that elevated levels of HA stem-specific antibody responses correlate with strengthened cross-protections. Our design strategy has proven effective in trimerizing HA ectodomains derived from both influenza A and B viruses, thereby providing a valuable reference for designing future influenza HA immunogens.

Exploiting membrane vesicles derived from avian pathogenic Escherichia coli as a cross-protective subunit vaccine candidate against avian colibacillosis.

Avian pathogenic Escherichia coli (APEC) is a notable pathogen that frequently leads to avian colibacillosis, posing a substantial risk to both the poultry industry and public health. The commercial vaccines against avian colibacillosis are primarily inactivated vaccines, but their effectiveness is limited to specific serotypes. Recent advances have highlighted bacterial membrane vesicles (MV) as a promising candidate in vaccine research. How to produce bacterial MVs vaccines on a large scale is a significant challenge for the industrialization of MVs. The msbB gene encodes an acyltransferase and has been implicated in altering the acylation pattern of lipid A, leading to a decrease in lipid A content in lipopolysaccharides (LPS). Here, we evaluated the immunoprotective efficacy of MVs derived from the LPS low-expressed APEC strain FY26ΔmsbB, which was an APEC mutant strain with a deletion of the msbB gene. The nitrogen cavitation technique was employed to extract APEC MVs, with results indicating a significant increase in MVs yield compared to that obtained under natural culture. The immunization effectiveness was assessed, revealing that FY26ΔmsbB MVs elicited an antibody response of laying hens and facilitated bacterial clearance. Protective efficacy studies demonstrated that immunization with FY26ΔmsbB MVs conferred the immune protection in chickens challenged with the wild-type APEC strain FY26. Notably, LPS low-carried MVs recovered from the mutant FY26ΔmsbB also displayed cross-protective capabilities, and effectively safeguarding against infections caused by O1, O7, O45, O78, and O101 serotypes virulent APEC strains. These findings suggest that MVs generated from the LPS low-expressed APEC strain FY26ΔmsbB represent a novel and empirically validated subunit vaccine for the prevention and control of infections by various APEC serotypes.

Evaluation of the cross-protection of the Vero cell-derived attenuated influenza vaccines with compound adjuvant, through intranasal immunization.

This study was to evaluate the sufficient safety and effect of the novel influenza vaccine program. It prepared new reassortant influenza virus, with high yield on Vero cells. According to the plaque counting, one dose LAIV was composed with 105 PFU of H1, H3, BY, and BV, respectively. Then mixed this LAIV with compound adjuvant, containing 500 µg/mL of carbopol971P and 50 µg/mL of tetanus toxin. That vaccination was called catt-flu. And it employed the GYZZ02 vaccine (commercialized freeze-dried LAIV, listed in China) as cohort analysis control. All mice received two doses of the vaccine, administered on days 0 and 14, respectively. That catt-flu program could induce more cross-protection with neutralizing antibody against heterogeneous types of influenza virus, not only based on HA but also NA protective antigen, through convenient nasal immunization, which had non-inferiority titter compared with the chicken embryo-derived GYZZ02 vaccine on safe and effect. The Vero cell-derived vaccine (LAIV) combined compound catt adjuvant (contain carbopol971P and tetanus toxin) could provide another safety and protective program of influenza vaccine by intranasal administration, as catt-flu program.

A Live Attenuated H1N1 Influenza Vaccine Based on the Mutated M Gene.

The influenza vaccines currently approved for clinical use mainly include inactivated influenza virus vaccines and live attenuated influenza vaccines (LAIVs). LAIVs have multiple advantages, such as ease of use and strong immunogenicity, and can provide cross-protection. In this study, the M gene of the PR8 virus was mutated as follows (G11T, C79G, G82C, C85G, and C1016A), and a live attenuated influenza virus containing the mutated M gene was rescued and obtained using reverse genetic technology as a vaccine candidate. The replication ability of the rescued virus was significantly weakened in both MDCK cells and mice with attenuated virulence. Studies on immunogenicity found that 1000 TCID50 of mutated PR8 (mPR8) can prime strong humoral and cellular immune responses. Single-dose immunization of 1000 TCID50 mPR8 was not only able to counter the challenge of the homologous PR8 virus but also provided cross-protection against the heterologous H9N2 virus.