Immuno-Protective Efficiency of the Bivalent Inactivated Vaccine Against Vibrio scophthalmi and Aeromonas salmonicida Infections in Turbot(Scophthalmus maximus L.)

Vibrio scophthalmi and Aeromonas salmonicida can cause high turbot mortality and huge economic losses.Presently,vaccination is the most promising method for preventing communicable diseases.In this study,we used formalin to kill V.scophthalmi and A.salmonicida cells,and mixed with the mineralized oil adjuvant(Montanide^(TM)ISA 763 AVG)to prepare the bivalent inactivated vaccine.The results showed that turbot inoculated with the bivalent inactivated vaccine exhibited strong tolerance to the infection of V.scophthalmi and A.salmonicida,and no obvious clinical symptoms and pathological changes were observed.The activities of enzymes lysozyme,acid phosphatase and complement C3 had significantly increased after the vaccination.The antibody titer response of vaccinated turbot was greatly boosted,which was positively connected with the immunological impact according to ELISA results.Simultaneously,the expression levels of immune-related genes such as MHC-IIα,MHC-IIβ,CD4,CD8,TNF-αand IL^(-1)βwere up-regulated,demonstrating that it might stimulate humoral and cellular immunological response in turbot.These findings highlight the potential of the bivalent inactivated vaccine for controlling V.scophthalmi and A.salmonicida infections in turbot.

Effectiveness of Hemorrhagic Fever with Renal Syndrome Bivalent Vaccine in China:A Metaanalysis

Objective To evaluate the effectiveness of Hemorrhagic Fever with Renal Syndrome(HFRS) bivalent vaccine in field.Methods The articles on effectiveness of HFRS bivalent vaccine were retrieved from Vip Database,China Journal Full-text Database,Wanfang database,China Hospital Knowledge Database,Chinese Biomedical Literature Database,MEDLINE and ProQuest.Two persons extracted data and evaluated the quality of data together for meta-analysis.Results Seven articles were included into the analysis,and two articles were random clinical trials,five were quasi-trials.Meta-analysis showed that the overall effectiveness of HFRS bivalent vaccine was 85%(95%confidence interval:53%-95%) within one year after vaccination,and the effectiveness in two-dose recipients and three-dose recipients was 87%(95%confidence interval:54%-96%) and 60%,respectively;it was 96%(95%confidence interval:78%-99%) within 2-5 years after vaccination,and the effectiveness in two-dose recipients and three-dose recipients was 95%(95%confidence interval:19%-100%) and 96%(95%confidence interval:70%-99%),respectively;it was 100%(only one article included) within 6-9.6 years after vaccination.The effectiveness in two-dose recipients was 88%(95%confidence interval:62%-96%) during 1-2.5 years after vaccination,and that in three-dose recipients was 94%(95%confidence interval:70%-99%) during 1-5 years after vaccination.Conclusions HFRS bivalent vaccine is effective in field,and there is no difference between two-dose recipients and three-dose recipients.We should do some further studies on the long-term effectiveness of HFRS bivalent vaccine and on the age of vaccine reception.

Observation on the Efficiency of the Mongolian Gerbil Kidney Tissue Culture Inactivated Bivalent Vaccine for Hemorrhagic Fever with Renal Syndrome

The Z 10 and Z 37 strains of hemorrhagic fever with renal syndrome (HFRS) virus and the Mongolian gerbil ( Merions unguiculatus ) kidney cells were used to prepare the inactivated bivalent vaccine. A phase Ⅱ clinical trial use of this vaccine was made in 750 Chinese volunteers. The results showed that the side reaction rate was 2.5% and the sero-conversion rate of neutralizing antibodies against Hantaan and Seoul viruses in the inoculated volunteers were 87.6% and 96.3% respectively.

Construction of a bivalent vaccine candidate against HAdV4/HAdV7 based on capsid-display strategy via Red-homologous recombination and counter-selection methodology

Human adenoviruses(HAdvs)are major respiratory pathogens.Specifically,human adenovirus type 4(HAdV4)and human adenovirus type 7(HAdV7)are known for causing fever and pneumonia,with docu-mented cases of fatalities among the population.In recent years,HAdV4/HAdv7 has been implicated in caus-ing substantial outbreaks,leading to increased morbidity in multiple countries.Most HAdV4 and HAdV7 infections have been reported in North America,Asia,Europe,Africa,South America,Oceania,and the Middle East.Most fatalities occurred in North America(the United States)and Asia(China and Singapore).Engineered recombinant adenoviruses have played a crucial role as vaccine vectors.In this study,we con-structed a recombinant adenovirus,Ad4ITRmut-Ad7E3,and evaluated it in vitro and in vivo.We observed that the replication rate of Ad4ITRmut-Ad7E3 was lower than that of the RI-67 strain,indicating that the mutation of inverted terminal repeats(ITRs)weakened the replication ability of HAdV4.Immunization of BALB/c mice with the bivalent Ad4ITRmut-Ad7E3 vaccine strain,administered by intraperitoneal injection and oral gavage,resulted in the elicitation of neutralizing antibodies targeting HAdV4 and HAdv7.This finding not only pro-vides a novel method and technique for the efficient construction of a polyvalent recombinant adenovirus vac-cine candidate against HAdV4 and HAdv7 but also against other prevalent adenovirus serotypes such as HAdV3,HAdV11,HAdV14,and HAdv55,from various regions.

Safety,immunogenicity,and preliminary efficacy of a randomized clinical trial ofomicron XBB.1.5-containing bivalent mRNA vaccine

Periodically updating coronavirus disease 19(COVID-19)vaccines that offer broad-spectrum protection is needed giventhe strong immune evasion by the circulating omicron sublineages.The effectiveness of prototype and BA.4/5-containing bivalent mRNA vaccines is reduced when XBB subvariants predominate.We initiated an observer-blinded,threearms study in 376 patients in Chinese individuals aged from 18 to 55 years old who had previously received three dosesCOVID-19 vaccine.Immunogenicity in terms of neutralizing antibodies elicited by a 30-mg dose of XBB.1.5-containingbivalent vaccine(RQ3027),a 30-mg dose of BA.2/BA.5-Alpha/Beta bivalent vaccine(RQ3025)and their precedent 30-mg Alpha/Beta(combined mutations)monovalent mRNA vaccine(RQ3013)and safety are primary and secondary endpoints,respectively.We recorded prescribed COVID-19 cases to explore the preliminary efficacy of three vaccines.RQ3027 and RQ3025 boosters elicited superior neutralizing antibodies(NAbs)against XBB.1.5,XBB.1.16,XBB.1.9.1,and JN.1 compared to RQ3013 at day 14 in participants without SARS-CoV-2 infection.All study vaccines were welltolerated without serious adverse reactions identified.The incidence rates per 1000 person-years of COVID-19 casesduring the 2nd-19th week after randomization were lowest in RQ3027.Overall,our data show that XBB.1.5-containingbivalent booster generated superior immunogenicity and better protection against newer severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants compared to BA.2/BA.5-containing bivalent and Alpha/Beta monovalentwith no new safety concerns.

Immunization effect of purified bivalent vaccine to haemorrhagic fever with renal syndrome manufactured from primary cultured hamster kidney cells

Haemorrhagic fever with renal syndrome (HFRS) is a worldwide epidemic plaguing over thirty nations. This disease has spread across 26 provinces, cities and autonomous regions of China with an annual onsets number of more than a hundred thousand and a mortality rate of 5% to 15%, accounting for over 80% of cases in the world, and threatening the safety and health of Chinese people. 1 Analysis of serum samples over recent years indicates that the plagued areas are expanding. Instead of a single type Ⅰ or Ⅱ strain, each area now has a combination with one type predominant. 2 These demographic changes revealed a shortcoming of the monovalent vaccine in use, urging China to develop a purified bivalent vaccine based on monovalent one. This research on clinical observation and immunization effects led to a purified bivalent vaccine manufactured by Changchun Institute of Biological Products, China from primary cultured hamster kidney cells.

Mucosal immune responses and protective efficacy in yellow catfish after immersion vaccination with bivalent inactivated Aeromonas veronii and Edwardsiella ictaluri vaccine

Mucosal vaccination,which has the potential to induce both mucosal and systemic immune responses,is considered the most suitable method of preventing infectious diseases in farmed fish.Aeromonas veronii and Edwardsiella ictaluri are two pathogenic bacteria found in yellow catfish and often infect the fish through mucosal surfaces.Delivery of a bivalent inactivated vaccine by injection has been shown to induce a strong systemic immune response against both bacterial infections.However,mucosal immune responses and protective efficiency induced by this inactivated vaccine administrated via immersion are yet to be investigated.We developed a bivalent vaccine containing formalin-inactivated A.veronii and E.ictaluri and evaluated the immune response in yellow catfish after immersion vaccination using body fluids biochemistry indices,agglutinating antibody titers,and the expression level of immune-related genes in the skin,gills,spleen,and head kidney.The activities of innate immune-related enzymes and specific agglutination antibody titers in body fluids,as well as the expression of innate and adaptive immune-related genes in both the mucosal and systemic tissues of vaccinated fish,were significantly higher than that in control fish.Next,we assessed the protective efficacy by a challenge model of virulent strains of E.ictaluri and A.veronii.The relative survival percent of vaccinated fish was 80%and 87%after challenging fish with E.ictaluri and A.veronii,respectively,which was higher than unvaccinated control fish(43%and 57%).These results confirm that the bivalent inactivated vaccine administered via immersion induces a strong mucosal immune response and confers good protection against both E.ictaluri and A.veronii.Our results also reinforce the notion that immersion vaccination could stimulate both mucosal and systemic immunity contributing to protection against pathogens.