A Case of Investigation and Diagnosis of Immune Thrombocytopenic Purpura After Vaccination of COVID-19 Inactivated Vaccine

Objective:Analyze the relationship between inoculating one case of the COVID-19 inactivated vaccine(Vero cell)and immune thrombocytopenic purpura to provide a reference for the standardized handling of adverse events following immunization.Methods:According to the"National Monitoring Program for Suspected Adverse Reactions to Vaccinations,"an on-site investigation,data collection and analysis,expert group diagnosis,and medical association assessment were conducted on a case of immune thrombocytopenic purpura in District A of Chongqing after vaccination with the inactivated COVID-19 vaccine.The assessment report was delivered to the three relevant parties,the case was reviewed,and the experience was summarized.Results:The investigation and diagnosis by the district-level vaccination abnormal reaction expert group concluded that the disease that occurred after vaccination with the COVID-19 inactivated vaccine was secondary immune thrombocytopenic purpura,an abnormal reaction to the vaccination.The medical damage was classified as Level II Grade B.The vaccine production enterprise raised objections to this conclusion.After re-assessment by the municipal-level medical association,the conclusion was consistent with that of the district-level medical association.The vaccine production enterprise did not raise any further objections.Conclusion:Through active collaboration among district and municipal-level medical associations,disease control institutions,and vaccination units,the recipients have been promptly and effectively treated,providing financial support for their subsequent treatment and safeguarding their rights.The investigation and disposal procedures for adverse events following immunization in Chongqing are clear,and the mechanism is sound.It is necessary to continue strengthening the monitoring of adverse events following immunization according to the existing plan and to ensure timely and standardized handling.Simultaneously,it is crucial to strengthen vaccine management and vaccination management.

Prevention and Nursing of Adverse Reactions of Novel Coronavirus Inactivated Vaccine (Vero Cells)

Objective:To discuss and analyze the causes of adverse reactions caused by the inactivated novel coronavirus vaccine(Vero cells),and to propose methods of prevention and care.Methods:A questionnaire was used to randomly select 229 adults who were vaccinated with the inactivated novel coronavirus vaccine(Vero cells)at Xi’an People’s Hospital(Xi’an Fourth Hospital).The adverse reactions were statistically analyzed.Results:Among the 229 adults vaccinated with the inactivated novel coronavirus vaccine(Vero cells),30 experienced vaccination reactions.The main reaction was local induration at the inoculation site,and dizziness was the primary systemic symptom.Conclusion:To reduce the incidence of adverse reactions to the inactivated novel coronavirus vaccine(Vero cells),it is necessary to effectively evaluate the health status of adults before vaccination,select the correct vaccination site,and strictly implement the rules of 3-inspections,7-checks,and 1-verification.Standardizing the operation process and providing thorough health education after vaccination can effectively reduce the occurrence of adverse reactions.

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.

Development of a Multivalent Inactivated Vaccine against Pathogenic Escherichia coli Infection in Forest Musk Deer

A multivalent inactivated Escherichia coli vaccine for forest musk deer by using serotypes O4,O26,and O139 with Al（OH）3 adjuvant was prepared.The vaccine did not cause any adverse reactions in forest musk deer.The immunogenic effects of the vaccine were experimentally investigated in pregnant and young forest musk deer.The serum antibody titers of pregnant and young forest musk deer were determined by performing the micro-agglutination test.The serum antibody titers of pregnant forest musk deer were more stable from 35th to 68th d after the third vaccination,and the serum antibody titers of four pregnant forest musk deer were maintained 25,25,25,and 24 on 68th d after the third vaccination.Young forest musk deer showed serum antibody titers which were obtained due to nursing.Young forest musk deer were administered the first intramuscular vaccine injection at an age of approximately 60 days due to a fall in maternal antibody titers.The serum antibody titers of young forest musk deer were higher after the third vaccination and maintained at approximately the same level until they were 137 days old.The maternal antibodies and the antibodies produced by young forest musk deer could be helpful for protecting the young musk deer from the infections of pathogenic Escherichia coli strains（serotypes O4,O26,and O139）for 137 days after birth（during the nursing period and the period when the forest musk deer were susceptible to diseases）.

Preparation of Purified and Inactivated HP-PRRS Vaccine

[Objective] The aim of this study was to improve the purification and protective potency of HP-PRRS inactivated vaccine. [Method] HP-PRRS virus that had been multiplied inside Marc-145 cells was collected and concentrated 50 times and then inactivated. Complete virions were separated and collected by chromatography with Sepharose 4 Fast Flow. Oil adjuvant was added to prepare purified inactivated vaccine. [Result] Viral protein was separated from other proteins by purification and the viral protein contents ranged from 76.7% to 82.4%, and 96% of the expected serum proteins were removed. Protective potency of purified vaccine was above 4/5 and positive conversion rate of antibody was over 86%, both higher than that of unpurified vaccine. The differences were significant. [Conclusion] The experiment il-lustrated that the immune efficacy of vaccine can be enhanced through concentrat- ing and purifying, while the non-viral protein can be removed, so that allergic reaction and stress response cadsed by vaccine inoculation can be avoided.

Porcine Interleukin-2 Expression in Insect Cells and Its Enhancement of Pig Immunity to Swine Influenza Virus Inactivated Vaccine

Mature porcine interleukin-2 （pIL-2） gene was amplified by PCR from the plasmid pGEM-T-pIL2 and cloned into the baculovirus pFastBacTM Dual vector of the Bac-to-Bac baculovirus expression system under the control of the PH promoter. Recombinant plL-2 （rpIL-2） expressed in Sf9 insect cells was detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunofluorescence assay. Western blot analysis confirmed that the rpIL-2 protein had a molecular mass of 20 kDa, which was larger than the molecular mass of the mature protein predicted based on its peptide sequence. The rpIL-2 protein induced in vitro proliferation of ConA-stimulated porcine splenocytes and enhanced in vivo protective immune responses induced by vaccinating the pigs with inactivated oil emulsion vaccine against swine influenza virus. The results showed that the rpIL-2 expressed in Sf9 insect cells has immunoenhancement effects; the finding lays the foundation for the preparation of a specific recombinant IL-2 protein and the development of a novel immune adjuvant of vaccines against various infectious porcine pathogens to increase the immunoprotective efficacy of vaccines.

Development of an Inactivated Iridovirus Vaccine Against Turbot Viral Reddish Body Syndrome

Turbot(Scophthalmus maximus L.) reddish body iridovirus(TRBIV) was propagated in turbot fin cells(TF cells) and inactivated as the TRBIV vaccine with its protection efficiency evaluated in this study.TF cells were cultured in 10% bovine calf serum(BCS)-containing MEM medium(pH7.0) at 22℃,in which TRBIV propagated to a titer as high as 105.6 TCID50 mL-1.The TRBIV was inactivated with 0.1% formalin and formulated with 0.5% aluminum hydroxide.The inactivated vaccine caused neither cytopathogenic effect(CPE) on TF cells nor pathogenic effect on turbots.After being administered with the vaccine twice via muscle injection,the turbot developed high-tittered TRBIV neutralizing antibodies in a dose-dependent manner.The vaccine protected the turbot from dying with an immunoprotection rate of 83.3% as was determined via subcutaneous vaccination in the laboratory and 90.5% via bath vaccination in turbot farms,respectively.The inactivated vaccine was very immunogenic,efficiently preventing tur-bot from death.It holds the potential of being applied in aquaculture.

A Semi-quantitative Serological Method to Assess the Potency of Inactivated Rabies Vaccine for Veterinary Use

Potency is one of the most important indexes of inactivated vaccines.A number of methods have been established to assay the potency,of which the NIH test and single-dose mouse protection test are the "prescribed methods".Here,we report a method to semi-quantitatively assay the potency of an inactivated rabies vaccine,which uses fewer animals and takes less time to complete.Depending on the quality requirements of a vaccine(e.g.minimum potency),a rabies reference vaccine is,for example,diluted to the minimum potency,and 50 μL of the dilution is taken to inoculate 10 mice.The same amount of the test rabies vaccine is inoculated into another 10 mice.After two weeks,all mice are bled and serum samples are assayed for viral neutralizing antibody by the fluorescent antibody virus neutralization(FAVN) test.By comparing the median and interquartile range of antibody titers of the reference vaccine with those of the test vaccine,the test vaccine potency can be semi-quantitatively judged as to whether it is in accord with the required quality.The reliability of this method was also confirmed in dogs.The procedure can be recommended for batch potency testing during inactivated rabies vaccine production.

Human IgM and IgG Responses to an Inactivated SARS-CoV-2 Vaccine

Objective:The ongoing COVID-19 pandemic warrants accelerated efforts to test vaccine candidates.To explore the influencing factors on vaccine-induced effects,antibody responses to an inactivated SARS-CoV-2 vaccine in healthy individuals who were not previously infected by COVID-19 were assessed.Methods:All subjects aged 18-60 years who did not have SARS-CoV-2 infection at the time of screening from June 19,2021,to July 02,2021,were approached for inclusion.All participants received two doses of inactivated SARS-CoV-2 vaccine.Serum IgM and IgG antibodies were detected using a commercial kit after the second dose of vaccination.A positive result was defined as 10 AU/mL or more and a negative result as less than 10 AU/mL.This retrospective study included 97 infection-naive individuals(mean age 35.6 years;37.1%male,62.9%female).Results:The seropositive rates of IgM and IgG antibody responses elicited after the second dose of inactivated SARS-CoV-2 vaccine were 3.1%and 74.2%,respectively.IgG antibody levels were significantly higher than IgM levels(P<0.0001).Sex had no effect on IgM and IgG antibody response after the second dose.The mean anti-IgG level in older persons(≥42 years)was significantly lower than that of younger recipients.There was a significantly lower antibody level at>42 days compared to that at 0-20 days(P<0.05)and 21-31 days(P<0.05)after the second dose.Conclusion:IgG antibody response could be induced by inactivated SARS-CoV-2 vaccine in healthy individuals(>18 years),which can be influenced by age and detection time after the second dose of vaccination.

Studies on Immunological Effect and Immunological Mechanism Avian Encephalomyelitis Oil Emulsion Inactivated Vaccine

Oil emulsion inactivated vaccine was prepared by susceptible embryos, with different strains of AEV. Four groups of normal chickens of 2 - 7 days of age were given injections for immunization, respectively. Another group was used as control. This study was expected to evaluate the immunological effect and discuss the immunological mechanism by means of five different experiments, i.e. the agar-gel precipitin test, the isolation of lymphokine, the isolation, purification and analysis of blood serum IgG, embryo-susceptibility test, and clinical and pathological examination. The results of these experiments indicated that oil emulsion inactivated vaccine is safe and effective. The chickens were normal when inoculated with AE strong virus after immunity at 4 and 37 weeks. Immunological mechanism is that the humoral immunity played an important role and celluar immunity exists, but it is not important in the process of the resistance to AEV.

Modeling the Long-term Antibody Response and Duration of Immune Protection Induced by an Inactivated,Preservative-free Hepatitis A Vaccine(Healive)in Children

Objective Long-term seroprotection via the hepatitis A vaccine is essential for the prevention of disease from the hepatitis A virus(HAV).Due to documented difficulties during decade-long follow-ups after receiving vaccines,statistical-modeling approaches have been applied to predict the duration of immune protection.Methods Based on five-year follow-up data from a randomized positive-controlled trial among Chinese children(1–8 years old)following a 0,6 months vaccination schedule,a power-law model accounting for the kinetics of B-cell turnover,as well as a modified power-law model considering a memory-B-cell subpopulation,were fitted to predict the long-term immune responses induced by HAV vaccination(Healive or Havrix).Anti-HAV levels of each individual and seroconversion rates up to 30 years after vaccination were predicted.Results A total of 375 participants who completed the two-dose vaccination were included in the analysis.Both models predicted that,over a life-long period,participants vaccinated with Healive would have close but slightly higher antibody titers than those of participants vaccinated with Havrix.Additionally,consistent with previous studies,more than 90%of participants were predicted to maintain seroconversion for at least 30 years.Moreover,the modified power-law model predicted that the antibody titers would reach a plateau level after nearly 15 years post-vaccination.Conclusions Based on the results of our modeling,Healive may adequately induce long-term immune responses following a 0,6 months vaccination schedule in children via induction of memory B cells to provide stable and durable immune protection.

Immune Effects of Porcine Interleukin-2,4 on Piglets Using as Immunopotentiator for PCV Inactivated Vaccine

[ Objective] To investigate the combined immunization of porcine circovirus 2 （PCV2） inactivated vaccine with PoIL-2,4. [ Methods] A total of 60 crossbred piglets were randomly divided into three groups, including the test group （ inoculation of 0.5 dose PCV2 inactivated vaccine with 0. 1 mL PoIL-2,4 at 14 and 28 day-old）, the positive control group （inoculation of 0.5 dose PCV2 inactivated vaccine） and the blank control group. [ Results ] The immune organ index, the lymphocyte transformation rates under different ages and the number of leukocytes and lymphocytes in peripheral blood increased significantly in test group, compared with control group. Moreover, the antibody and neutralizing antibody were also significantly higher in test group than that in control group. The clinical symptoms and pathological changes were not found, and the PC72 was not detected in serum and tissue after challenge test in test group, which indicated that the combined immunization of PCV2 inactivated vaccine with PoIL-2,4 significantly improved the lymphocyte transformation rate, effectively prevented the replication of PCV2 in organism, and enhanced the growth performance of piglets.

Preparation and Examination of Inactivated Emulsion Vaccine against Newcastle Disease, Infectious Bronchitis and H9 Subtype Avian Influenza

[ Objective] To prepare inactivated emulsion vaccine against Newcastle disease, infectious bronchitis and H9 subtype avian influenza. [ Method] Antigen fluid of Newcastle disease virus （NDV） La Sota strain, infectious bronchitis virus （IBV） M41 strain and HgN2 subtype avian in- fluenza virus （AIV） WD strain was prepared by propagation in chicken embryos, respectively. The antigen fluid was concentrated with FILTRON Cassette ultra-filtration system and inactivated by formalin. The antigen fluid of NDV, IBV and AIV was mixed at a volume ratio of 1：1：1. Then the mixture was emulsified by Span-80 and Tween-80 and added medical white oil as adjuvant. The sterility and physical characteristics of the prepared ND-IB-AI combined vaccine were detected. [ Result] The three batches of ND-IB-AI combined vaccine were germ-free, milky white, with water-in- oil pattern and with viscosity of 6.3 -6.8 s. The water and oil were not separated after rest at 37 ~C for 21 d or centrifugation. [ Conclusion] The three batches of ND-IB-AI combined vaccine were germ-free and reached the standard for physical characteristics of vaccines.

Agranulocytosis following injection of inactivated Japanese encephalitis vaccine(Vero cell):A case report

BACKGROUND Japanese encephalitis virus(JEV),a mosquito borne flavivirus,is the leading cause of viral encephalitis in Asia,in terms of frequency and severity.JEV infection is thought to confer lifelong immunity.With the near eradication of poliomyelitis,JEV is now the continent’s leading cause of childhood viral neurologic infection and disability.The most common clinical manifestation of JEV infection is acute encephalitis,and currently there is no specific antiviral therapy.Japanese Encephalitis Vaccine(JE-VC)is an effective prevention measure,including JE-VC,Live(JE-MB),and Inactivated JE-VC.CASE SUMMARY A 9-mo-old girl received injection of Inactivated JE-VC(Vero cell)(Liaoning Chengda,batch number 201611B17)on August 31,2017.On that night,she developed a fever with the body temperature up to 38.5°C,for which Ibuprofen Suspension Drops 1.25 mL was given as antipyretic treatment.On September 1,the patient developed apocleisis,and her parents noticed herpes in her oral cavity.The patient was sent to our hospital on September 3.Physical examination led to a diagnosis of herpetic stomatitis,for which Stomatitis Spray 1 puff,tid,Kangfuxin Liquid 2 mL,tid,and vitamin B20.5 tablet,tid,were prescribed.Routine blood tests for low fever on September 6,2017 revealed an absolute neutrophil count(ANC)of 0.62×109/L,hemoglobin(Hb)of 109 g/L,and platelet count(PLT)of 308×10^(12)/L,and the tests were monitored regularly thereafter.The patient was followed until July 26,2020,when routine blood tests revealed ANC 1.72×109/L,Hb 138 g/L,and PLT 309×1012/L,indicating that the neutropenia count had normalized.CONCLUSION This report attempts to bring to clinical attention that Inactivated JE-VC(Vero cell)might cause prolonged granulocytopenia or even agranulocytosis.

Antibody Dynamic Changes in SPF Chickens and SPF Ducks Immuned with Recombinant Avian Influenza Virus H5 Subtype Bivalent Inactivated Vaccine

To study the immune effect of recombinant avian influenza virus H5 subtype bivalent inactivated vaccine （ HSN1, Re-6 strain ＋ Re-4 strain） and to provide the basis for formulating reasonable immune procedure of avian influenza vaccine in clinical practice. A total of 12 batches of vaccines from three companies were used for the iannune of SPF chickens and SPF ducks. Each chicken or duck serum was separately collected every 3 weeks until the immunization up to the 24^th week. The serum antibody titers of Re-6 and Re-4 were detected. The results showed that the HI titers of the inoculated SPF chickens and SPF ducks roached the peak when the immune time were the 6^th and 3^rd week after the first immunization respectively; then the titer decreased gradually as time prolonged; the highest titer of SPF chickens was greater than that of SPF ducks; the high titer duration of SPF chickens were longer than that of SPF ducks ; and all the vaccines from the three companies showed a good immune effect.

Pilot-Scale Production of Lyophilized Inactivated Rabies Vaccine Candidate in Vero Cells under Fully Animal Component-Free Conditions Using Microcarrier Technology and Laboratory Animal Trials

The upstream process was carried out in an animal component-free medium on Cytodex 1 microcarriers. Recombinant trypsin is a non-animal derived protease used as an alternative to animal-derived trypsin. To inactivate recombinant trypsin, a soybean trypsin inhibitor (STI) should be added to the medium. A protocol was first tested in T-flasks and then passaged to 500 mL and 3 L spinner flasks. Cell detachment was completed in 10 - 12 min, and 0.4 g/L STI was added to a 3L spinner, and cells were transferred into a 30 L stirred tank bioreactor. On day 5, the cell density had reached its maximum (around 1.8 × 106 cells/mL). At an MOI of 0.3 with serum-free medium conditions, cell infection yielded a maximal rabies virus titer of 1.82 × 107 FFU/mL at 5 days. All cell culture conditions and virus growth kinetics in serum-free media were investigated. In conclusion, Vero cells were grown on Cytodex 1 with serum-free media and a high amount of rabies virus was obtained. A mouse challenge was used to determine the immune response to an inactivated rabies virus vaccine candidate. Also, we evaluated inactive rabies vaccine candidate safety, and immunogenicity in mice, sheep, horses, and cattle. We found that no horses, sheep, or cattle who were given vaccine IM at 3.2 IU/dose exhibited any clinical sign of disease and all developed high VNA titers (up to 10.03 IU/mL) by 3 - 4 WPI. After the accelerated stability studies, the lyophilized inactivated rabies vaccine candidate showed enough antigenic potency (2.6 IU/mL) in the mouse challenge test. Also, 18-month long-term stability studies showed enough immune response (1.93 IU/mL) on day 14. The activity of the vaccine candidate showed a good immune response and safety criteria that meet WHO requirements. This is the first pilot-scale mammalian cell-based viral rabies vaccine production study in Türkiye that used microcarriers.

Establishment of animal model for potency evaluationof inactivated SARS virus experimental vaccine

The purpose of this study was to test the effectiveness of source virus strain for the manufacture of the inactivated SARS virus vaccine, and establish an experimental method and preliminary standard for potency evaluation. Mice were divided into groups for being immunized with corresponding serially diluted experimental SARS virus inactivated vaccine. And the rabbits were immunized with undiluted vaccine. Challenge assay was conducted with a heterologous SARS virus. And the neutralization antibody was determined with plaque reduction neutralization test (PRNT), to which the neutralization antibody in the convalescent serum of SARS patients was compared. The experimental vaccine viral strains were proved to be suitable for manufacturing the vaccine. Mice immunized by vaccines of serial dilutions were able to elicit neutralizing antibody. The antibody titer from mice immunized with the undiluted vaccine could reach up to 1∶495.2, while those of rabbits immunized with the undiluted vaccine could reach a GMT of 55.0-79.9. The capability of the antibody to neutralize the virus from Guangdong is more efficient than that from Beijing. The GMT of neutralizing antibody in SARS convalescents living in south and north China ranged from 50.12 to 54.95, and the titers of convalescents from north China were higher than those from south China. Mice and rabbits used as the model for evaluation of potency are of sensitivity, and the test is of reproducibility. The candidate challenge viral strains showed a relatively consistent effect on evaluating antibodies produced by various batches and different vaccine-source strains, hence they can be used to evaluate potency of the vaccine. The method for testing the vaccine potency and the evaluation standard was established preliminarily.

Investigation of the epidemiology,pathogenicity and immunogenicity of Bordetella bronchiseptica isolated from cats and dogs in China from 2021 to 2023

Bordetella bronchiseptica(Bb)is recognized as a leading cause of respiratory diseases in dogs and cats.However,epidemiological data on Bb in dogs and cats in China are still limited,and there is no commercially available vaccine.Live vaccines containing Bb that are widely used abroad are generally efective but can establish latency and potentially reactivate to cause illness in some immunodefcient vaccinated recipients,raising safety concerns.In this study,34 canine-derived and two feline-derived Bb strains were isolated from 1809 canine and 113 feline nasopharyngeal swab samples collected from eight provinces in China from 2021 to 2023.The PCR results showed that the percentage of positive Bb was 22.94%(441/1922),and more than 90%of the Bb isolates had four virulence factor-encoding genes(VFGs),namely,fhaB,prn,betA and dnt.All the isolated strains displayed a multidrug-resistant phenotype.The virulence of 10 Bb strains isolated from dogs with respiratory symptoms was tested in mice,and we found that eight isolates were highly virulent.Furthermore,the eight Bb isolates with high virulence were inactivated and intramuscularly injected into mice,and three Bb strains(WH1218,WH1203 and WH1224)with the best protective efcacy were selected.Dogs immunized with these three strains exhibited strong protection against challenge with the Bb feld strain WH1218.Ultimately,the WH1218 strain with the greatest protection in dogs was selected as the vaccine candidate.Dogs and cats that received a vaccine containing 109 CFU of the inactivated WH1218 strain showed complete protection against challenge with the Bb feld strain WH1218.This study revealed that Bb is an important pathogen that causes respiratory diseases in domestic dogs and cats in China,and all the isolates exhibited multidrug resistance.The present work contributes to the current understanding of the prevalence,antimicrobial resistance,and virulence genes of Bb in domestic dogs and cats.Additionally,our results suggest that the WH1218 strain is a promising candidate safe and efcacious inactivated Bb vaccine.

Evaluation of antibody responses in healthy individuals receiving SARS-CoV-2 inactivated vaccines

Inactivated coronavirus disease 2019(COVID-19)vaccines such as CoronaVac and BBIBP-CorV have been widely used in China.However,more investigation is still needed to understand antibodies'duration and effectiveness against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants in the real world.In this study,575 participants who had been vaccinated with two or three doses of the inactivated vaccine were recruited.Serum samples were collected and tested for anti-spike IgG and neutralizing antibodies against SARS-CoV-2(original strain,Dela,and Omicron).Unsurprisingly,a third dose of the vaccine significantly enhanced antibody responses against SARS-CoV-2 and its variants.However,despite a booster dose,the neutralizing antibody levels against Omicron,particularly the BA.5.2 subvariant,remained low.There was no sex bias,but an age bias was observed.Notably,the predominant IgG subclass antibodies were IgG1 and IgG2,with a much lower level of IgG4.After the booster shot,the ratio of IgG4 to IgG1 significantly increased.The observation of IgG1 to the IgG4 class switch after repeated inactivated vaccinations underscores the importance of continuous monitoring of subclass antibody responses.Further clinical investigations are required to understand the implications of this class switch for optimizing immunization strategies.

H2 strain attenuated live hepatitis A vaccines:protective efficacy in a hepatitis A outbreak

AIM:To investigate the protective efficacy of H2 strain attenuated live hepatitis A vaccines (H2-strain vaccines) in hepatitis A (HA) outbreaks.METHODS:With the permission of their parents, 5551 pre-school and grade 1-3 primary school children were inoculated with 1 dose (10(6.5) TCID(50)) of H2 strain vaccines in a nonrandomized, controlled trial conducted in Fucheng County, Hebei Province in May 1997.Another 6485 children in the same grades and compatible in gender and age were enrolled as controls. Epidemiological and serological survey was conducted to evaluate the protective efficacy of the vaccines. ELISA was used to detect serum IgM anti-HAV.RESULTS:HA outbreak started in early May 1998, peaked in the middle of the same month, and lasted about 80 days. Overall 302 HA cases were found, 192(63.58%) were 5-9 years old. One vaccinee and 25 control cases were found to have hepatitis A, which account for 0.28% (1/356) and 5.92% (25/422) of all vaccinees and controls in the 14 villages, respectively. The protective efficacy of vaccines was 95.27% (95% CI: 85.83%-104.72%). In subjects tested for anti-HAV IgM from 13 villages, 1(0.40%) overt and 11(4.06%) asymptomatic HAV cases were found in 271 vaccinees but 21(6.69%) of overt and asymptomatic ones were found in 314 controls.CONCLUSION:H2 strain vaccines were excellent in preventing overt hepatitis A,but not so effective in preventing asymptomatic hepatitis A virus infection.A booster dose might be needed to get permanent reliable immunity.