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.

Safety and immunogenicity of inactivated SARS-CoV-2 vaccine in high-risk occupational population:a randomized,parallel,controlled clinical trial

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (COVID-19) have a substantial burden on health-care systems around the world. This is a randomized parallel controlled trial for assessment of the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, aiming to determine an appropriate vaccination interval of the vaccine for high-risk occupational population.Methods: In an ongoing randomized, parallel, controlled phase IV trial between January and May 2021 in Taiyuan City, Shanxi Province, China, we randomly assigned the airport ground staff and public security officers aged 18 to 59 years to receive two doses of inactivated SARS-CoV-2 vaccine at 14 days, 21 days, or 28 days. The serum neutralizing antibody to live SARS-CoV-2 was performed at baseline and 28 days after immunization. Long-term data are being collected. The primary immunogenicity endpoints were neutralization antibody seroconversion and geometric mean titer (GMT) at 28 days after the second dose. Analysis of variance (ANOVA), chi-square, and logistic regression analysis were used for data analysis.Results: A total of 809 participants underwent randomization and received two doses of injections: 270, 270, 269 in the 0-14, 0-21, and 0-28 vaccination group, respectively. By day 28 after the second injection, SARS-CoV-2 neutralizing antibody of GMT was 98.4 (95%CI: 88.4-108.4) in the 0-14 group, which was significantly lower compared with 134.4 (95%CI: 123.1-145.7) in the 0-21 group (P < 0.001 vs 0-14 group) and 145.5 (95%CI: 131.3-159.6) in the 0-28 group (P < 0.001 vs 0-14 group), resulting in the seroconversion rates to neutralizing antibodies (GMT ≥ 16) of 100.0% for all three groups, respectively. The intention-to-treat (ITT) analysis yielded similar results. All reported adverse reactions were mild.Conclusions: Both a two-dose of inactivated SARS-CoV-2 vaccine at 0-21 days and 0-28 days regimens significantly improved SARS-CoV-2 neutralizing antibody level compared to the 0-14 days regimen in high-risk occupational population, with seroconversion rates of 100.0%.

Immunogenicity Evaluation of a SARS-CoV-2 BA.2 Subunit Vaccine Formulated with CpG 1826 plus alum Dual Adjuvant

Objective The present study aimed to evaluate the immunogenicity of BA.2 variant receptor binding domain(RBD)recombinant protein formulated with CpG 1826 plus alum dual adjuvant.Methods The BA.2 variant RBD(residues 308-548)fusing TT-P2 epitope was obtained from prokaryotic expression system,purification technology and dialysis renaturation,which was designated as Sot protein.The soluble Sot protein formulated with CpG 1826 plus alum dual adjuvant was designated as Sot/CA subunit vaccine and then the BALB/c mice were intramuscularly administrated with two doses of the Sot/CA subunit vaccine at 14-day interval(day 0 and 14).On day 28,the number of effector T lymphocytes secreting IFN-γand IL-4 in mice spleen were determined by enzyme-linked immunospot(ELISpot)assay.The serum IgG,IgG1 and IgG2a antibodies were examined by enzyme-linked immunosorbent assay(ELISA).In addition,the level of neutralizing antibodies(NAbs)induced by Sot/CA subunit vaccine was also evaluated by the microneutralization assay.Results The high-purity soluble Sot protein with antigenicity was successfully obtained by the prokaryotic expression,protein purification and dialysis renaturation.The Sot/CA subunit vaccine induced a high level of IgG antibodies and NAbs,which were of cross-neutralizing activity against SARS-CoV-2 BA.2 and XBB.1.5 variants.Meanwhile,Sot/CA subunit vaccine also induced a high level of effector T lymphocytes secreting IFN-γ(635.00±17.62)and IL-4(279.20±13.10),respectively.Combined with a decreased IgG1/IgG2a ratio in the serum,which indicating Sot/CA subunit vaccine induced a Th1-type predominant immune response.Conclusion The Sot protein formulated with CpG 1826 plus alum dual adjuvant showed that the excellent cellular and humoral immunogenicity,which provided a scientific basis for the development of BA.2 variant subunit vaccines and references for the adjuvant application of subunit vaccines.

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.

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.

COVID-19 vaccination produces exercise-responsive SARS-CoV-2 specific T-cells regardless of infection history

Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillance and protect against severe coronavirus disease 2019(COVID-19).We sought to determine if COVID-19 vaccination would elicit exercise-responsive SARS-CoV-2 T-cells and transiently alter nAb titers.Methods:Eighteen healthy participants completed a 20-min bout of graded cycling exercise before and/or after receiving a COVID-19 vaccine.All major leukocyte subtypes were enumerated before,during,and after exercise by flow cytometry,and immune responses to SARS-CoV-2 were determined using whole blood peptide stimulation assays,T-cell receptor(TCR)-βsequencing,and SARS-CoV-2 nAb serology.Results:COVID-19 vaccination had no effect on the mobilization or egress of major leukocyte subsets in response to intensity-controlled graded exercise.However,non-infected participants had a significantly reduced mobilization of CD4+and CD8+naive T-cells,as well as CD4+central memory T-cells,after vaccination(synthetic immunity group);this was not seen after vaccination in those with prior SARS-CoV-2 infection(hybrid immunity group).Acute exercise after vaccination robustly mobilized SARS-CoV-2 specific T-cells to blood in an intensity-dependent manner.Both groups mobilized T-cells that reacted to spike protein;however,only the hybrid immunity group mobilized T-cells that reacted to membrane and nucleocapsid antigens.nAbs increased significantly during exercise only in the hybrid immunity group.Conclusion:These data indicate that acute exercise mobilizes SARS-CoV-2 specific T-cells that recognize spike protein and increases the redistribution of nAbs in individuals with hybrid immunity.

Development of donor specific antibodies after SARS-CoV-2 vaccination:What do we know so far?

Vaccination against Coronavirus disease-19(COVID-19)was pivotal to limit spread,morbidity and mortality.Our aim is to find out whether vaccines against COVID-19 lead to an immunological response stimulating the production of de novo donor specific antibodies(DSAs)or increase in mean fluorescence intensity(MFI)of pre-existing DSAs in kidney transplant recipients(KTRs).This study involved a detailed literature search through December 2nd,2023 using PubMed as the primary database.The search strategy incorporated a combination of relevant Medical Subject Headings terms and keywords:"COVID-19","SARS-CoV-2 Vaccination","Kidney,Renal Transplant",and"Donor specific antibodies".The results from related studies were collated and analyzed.A total of 6 studies were identified,encompassing 460 KTRs vaccinated against COVID-19.Immunological responses were detected in 8 KTRs of which 5 had increased MFIs,1 had de novo DSA,and 2 were categorized as either having de novo DSA or increased MFI.There were 48 KTRs with pre-existing DSAs prior to vaccination,but one study(Massa et al)did not report whether pre-existing DSAs were associated with post vaccination outcomes.Of the remaining 5 studies,35 KTRs with pre-existing DSAs were identified of which 7 KTRs(20%)developed de novo DSAs or increased MFIs.Overall,no immunological response was detected in 452(98.3%)KTRs.Our study affirms prior reports that COVID-19 vaccination is safe for KTRs,especially if there are no pre-existing DSAs.However,if KTRs have pre-existing DSAs,then an increased immunological risk may be present.These findings need to be taken cautiously as they are based on a limited number of patients so further studies are still needed for confirmation.

SARS-CoV-2 vaccine research and development: Conventional vaccines and biomimetic nanotechnology strategies

The development of a massively producible vaccine against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),a novel coronavirus,is essential for stopping the current coronavirus disease(COVID-19)pandemic.A vaccine must stimulate effective antibody and T cell responses in vivo to induce long-term protection.Scientific researchers have been developing vaccine candidates for the severe acute respiratory syndrome(SARS)and Middle East respiratory syndrome(MERS)since the outbreaks of these diseases.The prevalence of new biotechnologies such as genetic engineering has shed light on the generation of vaccines against novel viruses.In this review,we present the status of the development of coronavirus vaccines,focusing particularly on the biomimetic nanoparticle technology platform,which is likely to have a major role in future developments of personalized medicine.

A Vaccine Based on the Receptor-Binding Domain of the Spike Protein Expressed in Glycoengineered Pichia pastoris Targeting SARS-CoV-2 Stimulates Neutralizing and Protective Antibody Responses

In 2020 and 2021,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),a novel coronavirus,caused a global pandemic.Vaccines are expected to reduce the pressure of prevention and control,and have become the most effective strategy to solve the pandemic crisis.SARS-CoV-2 infects the host by binding to the cellular receptor angiotensin converting enzyme 2(ACE2)via the receptor-binding domain(RBD)of the surface spike(S)glycoprotein.In this study,a candidate vaccine based on a RBD recombinant subunit was prepared by means of a novel glycoengineered yeast Pichia pastoris expression system with characteristics of glycosylation modification similar to those of mammalian cells.The candidate vaccine effectively stimulated mice to produce high-titer anti-RBD specific antibody.Furthermore,the specific antibody titer and virus-neutralizing antibody(NAb)titer induced by the vaccine were increased significantly by the combination of the double adjuvants Al(OH)_(3) and CpG.Our results showed that the virus-NAb lasted for more than six months in mice.To summarize,we have obtained a SARS-CoV-2 vaccine based on the RBD of the S glycoprotein expressed in glycoengineered Pichia pastoris,which stimulates neutralizing and protective antibody responses.A technical route for fucose-free complex-type N-glycosylation modified recombinant subunit vaccine preparation has been established.

SARS-Cov-2 Delayed Tokyo 2020 Olympics: Very Recent Advances in COVID-19 Detection, Treatment, and Vaccine Development Useful Conducting the Games in 2021

The novel coronavirus (SARS-Cov-2) delayed the Tokyo 2020 Games. The traveling by air, rail, road, and sea inside and outside the countries has stopped to contain the virus. The amount of money lost and assistance needed to reschedule and conduct the Games in 2021 have been estimated. With more than one billion population is under the semi-locked down and movement of people is restricted, athletes cannot prepare at home and participate in the Games. The COVID-19 outbreak has spread around the world;it has already infected 5.7 million people and caused 355,000 deaths reported on May 28, 2020 and the figures increasing every day. The publication of this article is important as the postponement of the Olympics has costed Japan $6 billion and the organizers have worked very hard for seven years. If the Games are conducted in 2021, it will be the—beginning of the world recovery—from big COVID-19 pandemic. In this communication, the development in testing, treatment, and vaccine preparation for SARS-Cov-2 have occurred so far in different countries and companies have been discussed to know the possibilities if the pandemic can be overcome and the Games can be conducted in 2021.

Research Progress on a SARS-CoV-2 Vaccine in China

Although many countries have controlled the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through strict management, there are still many countries with record-breaking numbers of new cases. Therefore, it is very important to develop a vaccine that can cause wide cross reactivity in clinical trials. At present, more than 90 vaccines are entering clinical trials and progressing smoothly, including inactivated vaccines, adenovirus-vectored vaccines and other types of vaccines. Here, we review and summarize the efficacy and potential threats of a SARS-CoV-2 vaccine. We reviewed whole-virus vaccines, adenovirus-subunit vaccines and recombinant protein vaccines and discussed the positive and negative consequences of a SARS-CoV-2 vaccine. However, there are still heated debates on the mechanism, effectiveness, and breadth of protection. In conclusion, this study can predict the risk of new coronavirus outbreaks in the future by discussing the research and development status of new coronavirus vaccines in China and other countries. Looking to the future, it is important to mine the large amount of data generated in clinical trials of universal new coronavirus vaccines to ensure that these vaccine programs are equally useful in the face of new coronavirus mutations.

Efficacy and safety profile of two-dose SARS-CoV-2 vaccines in cancer patients:An observational study in China

BACKGROUND The new coronavirus severe acute respiratory syndrome coronavirus 2(SARSCoV-2)has produced a global pandemic of coronavirus disease 2019(COVID-19),resulting in modifications to public health policies on a universal scale.SARSCoV-2 vaccine has evolved as the most effective and secure way for protecting healthy individuals against COVID-19.Patients with cancer were excluded from clinical trials due to their increased COVID-19 risk and current immunosuppressing therapy.Safety and effectiveness evidence is insufficient for SARS-CoV-2 vaccination in cancer patients.AIM To assess the efficacy and safety of two-dose SARS-CoV-2 vaccines in cancer patients.METHODS A multicenter observational study was performed at ten Chinese hospitals between January 1,2021 and December 31,2021.Each participant in the research received two doses of vaccination.A total of 215 healthy people were screened and 132 eligible patients with cancer were recruited.In order to verify the safety of the second dose of the vaccine,a side-effect report was compiled.Two weeks following the second vaccination dose,subjects underwent an analogous questionnaire survey.Utilizing a magnetic particle-based chemiluminescence immunoassay,serum levels of anti-SARS-CoV-2 immunoglobulin G(IgG)antibodies were measured to determine the effectiveness of vaccination.IgG levels≥10 AU/mL were considered seropositive.RESULTS All the 347 eligible patients completed the follow-up,and anti-SARS-CoV-2 IgG antibodies were detected.Local pain at the injection location was the most common side effect mentioned by all responders,with an increased incidence in cancer patients than the healthy people after the second dose vaccine(17.2%vs 9.1%;P=0.035).There was no significant difference in headache,urticaria,or other adverse reactions between patients with cancer and healthy people.In the group of cancer patients,the seropositivity incidence was 83.3%,while it was 96.3%in the group of healthy people.In the group of cancer patients,the seropositivity incidence and antibody levels were significantly lower(P<0.001).This analysis showed a poorer response rate in patients on active immunosuppressive treatment and elderly cancer patients.CONCLUSION Two-dose Chinese vaccines are effective and safe in cancer patients.However,further research is required on the efficacy in elderly cancer patients and those on active immunosuppressive treatment.

Thyrotoxicosis in patients with a history of Graves'disease after SARS-CoV-2 vaccination(adenovirus vector vaccine):Two case reports

BACKGROUND Vaccines against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which were approved for emergency use have been administered on a large scale globally to contain the pandemic coronavirus disease 2019(COVID-19)and to save lives.Vaccine safety is one of the issues under surveillance and a possible correlation between vaccines and thyroid function has been reported.However,reports of the impact of coronavirus vaccines on those with Graves’disease(GD)are rare.CASE SUMMARY This paper presents two patients with underlying GD in remission,both developed thyrotoxicosis and one developed thyroid storm following the adenovirus-vectored vaccine(Oxford-AstraZeneca,United Kingdom).The objective of this article is to raise awareness regarding a possible association between COVID-19 vaccination and the onset of thyroid dysfunction in patients with underlying GD in remission.CONCLUSION Receiving either the mRNA or an adenovirus-vectored vaccine for SARS-CoV-2could be safe under effective treatment.Vaccine induced thyroid dysfunction has been reported,but the pathophysiology still not well understood.Further investigation is required to evaluate the possible predisposing factors for developing thyrotoxicosis especially in patients with underlying GD.However,early awareness of thyroid dysfunction following vaccination could avoid a lifethreatening event.

Sex differences in SARS-CoV-2 infections,anti-viral immunity and vaccine responses

The COVID-19 pandemic has revealed sex-based differences in anti-viral responses,with a higher rate of SARS-CoV-2 infections as well as a higher rate of morbidity and mortality in men than in women.Males and females also show disparate immune responses to COVID-19 infection,which may be important contributors to lower rates of infection,disease severity and deaths in women than in men.Here,the authors review sex differences in SARS-CoV-2 infections,anti-viral immunity and vaccine responses,putting forth the importance of sex,the underappreciated variables in vaccine response and disease infectivity.

New and Newer Vaccines for SARS-CoV-2 Variants. Are the Major Vaccine Developers on the Right Track, Or Is Delipidation the Answer?

Background: Global Covid-19 pandemic has led to remarkable scientific achievements resulting in the development and rapid implementation of vaccines towards the original wild-type SARS-CoV-2 virus. Most Covid-19 vaccines are targeted to only one protein (the Spike protein) on the virus. SARS-CoV-2 that causes Covid-19 naturally undergoes multiple mutations over time. Such mutations can be inconsequential or have dire consequences. The lack of effectiveness of current vaccines towards mutated variants of Covid-19 is of major concern. The objective of this study is to describe an optimal solvent system that creates, via delipidation, a non-synthetic, host-derived or nonhost-derived modified viral particle that has its lipid envelope removed, exposing hidden undenatured proteins from within the virus, that generate a positive immunologic response when administered into a host, thereby providing a vaccine that offers strong and broad protection against the virus. Methods: Lipid removal from viruses by specific procedures renders the exposure of hidden proteins. Protection by antibodies to all of the virus’ protein types has shown to be far superior to protection by antibodies that are created by a single protein type. Results: Published studies with the Hepatitis virus, Pestivirus and HIV virus have reported the wide range of applications with this delipidation approach resulting in effectively long-term and broad protection vaccines. Conclusion: Mutations are rendering existing vaccines less effective. New approaches to obtain a more permanent vaccine that minimizes the effects of mutation are obtainable by delipidation of the viral particle and thereby creating vaccines that are more permanent with broad protection.

Universal COVID-19 Vaccine Targeting SARS-CoV-2 Envelope Protein

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had caused over 382 million cases and over 2.7 million deaths globally as of 23 March 2021. By that date, at least 10 SARS-CoV-2 variants had emerged. The transmissibility and lethality of the variants are higher than those of the Wuhan reference strain. Therefore, a universal vaccine for the reference strain and all variants (present and future) is indispensable. The coronavirus envelope (E) protein is an integral membrane protein crucial to the viral lifecycle and the pathogenesis of coronaviruses. The SARS-CoV-2 E protein has a postsynaptic density protein 95/Drosophila disc large tumor suppressor/zonula occludens-1 (PDZ) binding motif (PBM), and its interaction with PDZ-domain-2 of the human tight junction protein may interrupt the integrity of lung epithelium. Furthermore, the SARS-CoV-2 E protein itself is a homopentameric cation channel viroporin, which may be involved in viral release. This protein is thus a potential target for the development of a universal COVID-19 vaccine, because of its highly conserved amino acid sequence. The variant mutations occur mainly in the spike protein, and conservation of E protein remained in most Variants of Concern (VOC). Only one of the extant VOC have mutations in the E protein that P71L mutation occurs in the South African variant 501Y.V2 (B.1.351). If a vaccine is designed to target E protein, two scenarios are possible: 1) SARS-CoV-2 maintains a highly conserved E protein amino acid sequence, rendering the virus consistently or permanently susceptible to the vaccine;or 2) the E protein mutates and new variants evolve accordingly. In scenario 2, the tertiary structure and function of the E protein homopentameric cation channel viroporin, PBM, or other aspects affecting pathogenicity would be attenuated. Either scenario would thus ameliorate the pandemic. I therefore propose that a vaccine targeting the SARS-CoV-2 E protein would be effective against the Wuhan reference strain and all current and future SARS-CoV-2 variants. Efforts to create E protein-based vaccines are ongoing. Further research and clinical trials are needed to realize this universal COVID-19 vaccine.

Pooled analysis of efficacy of the fourth mRNA-based COVID-19 vaccine dose in eliciting anti-SARS-CoV-2 serum antibody response in the general immunocompetent population

Objective:Since the opportunity of widespread administration of the fourth mRNA-based coronavirus disease 2019(COVID-19)vaccine dose remains controversial,this article provides a pooled analysis of the efficacy of the second COVID-19 mRNA-based homologous vaccine booster in eliciting anti-SARS-CoV-2 serum antibody response in general immunocompetent populations.Methods:We conducted a digital search in Medline using the keywords"fourth dose"or"second booster"and"antibodies"and"COVID-19"or"SARS-CoV-2"and"BNT162b2"or"mRNA-1273",to identify all clinical studies which evaluated the anti-SARS-CoV-2 serum antibody response after the fourth mRNA-based COVID-19 homologous vaccine dose administration in general immunocompetent populations compared to the response seen before its administration and after the first booster.Results:Four studies totaling 571 recipients of the second mRNA-based COVID-19 vaccine booster were finally included in our analysis.The weighted mean difference(WMD)ratio of anti-SARS-CoV-2 serum antibodies levels measured after and before administration of the fourth vaccine dose was 9.7(95%CI,6.5-12.9)in those receiving BNT162b2 and 12.0(95%CI,5.8-18.2)in those receiving mRNA-1273,respectively.The WMD ratio of anti-SARS-CoV-2 serum antibodies levels measured at the peak of the fourth and third vaccine doses was 1.4(95%CI,1.2-1.7)in those receiving BNT162b2 and 1.9(95%CI,1.5-2.4)in those receiving mRNA-1273,respectively.Conclusion:Our data confirm the efficacy of the fourth mRNA-based COVID-19 vaccine dose in restoring a satisfactory level of anti-SARS-CoV-2 serum antibodies,though such effectiveness seems only marginally superior to that of the first booster.

Clinical application of COVID-19 vaccine in liver transplant recipients

Background:Solid organ transplant(SOT)activities,such as liver transplant,have been greatly influenced by the pandemic of coronavirus disease 2019(COVID-19),a disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Immunosuppressed individuals of liver transplant recipients(LTRs)tend to have a high risk of COVID-19 infection and related complications.Therefore,COVID-19 vaccination has been recommended to be administered as early as possible in LTRs.Data sources:The keywords“liver transplant”,“SARS-CoV-2”,and“vaccine”were used to retrieve articles published in PubMed.Results:The antibody response following the 1st and 2nd doses of vaccination was disappointingly low,and the immune responses among LTRs remarkably improved after the 3rd or 4th dose of vaccination.Although the 3rd or 4th dose of COVID-19 vaccine increased the antibody titer,a proportion of patients remained unresponsive.Furthermore,recent studies showed that SARS-CoV-2 vaccine could trigger adverse events in LTRs,including allograft rejection and liver injury.Conclusions:This review provides the recently reported data on the antibody response of LTRs following various doses of vaccine,risk factors for poor serological response and adverse events after vaccination.

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.

Immune response to inactivated bacterial vector carrying the recombinant K39 antigen of Leishmania infantum in mice

Objective:To evaluate the immunological response elicited by an inactivated bacterial vector carrying the K39 antigen of Leishmania infantum,and a purified antigen.Methods:Mice were subjected to the following treatments:(1)Purified recombinant K39(rK39)protein at a 20μg dose with complete Freund’s adjuvant;(2)Inactivated Escherichia coli(BL21 DE3)carrying the K39 protein at an equivalent total protein content of 200μg;(3)Inactivated bacteria lacking the K39 protein;(4)Non-immunized control animals.Serological monitoring was performed.All groups were challenged by intraperitoneal injection of 10^(7) Leishmania infantum promastigotes.After euthanasia,the liver and spleen were collected to analyze the levels of TNF,IFN-γ,IL-12,IL-4,and IL-10.Results:Mice immunized with purified rK39 or the inactivated bacterial vector carrying the K39 antigen of Leishmania infantum showed a long-lasting immune response with high levels of polyclonal antibodies specifically recognizing the recombinant proteins.The IgG1 subclass was the predominant immunoglobulin;however,the induction of IgG2a and the profile of cytokines produced were indicative of the induction of a mixed-type response.Conclusions:The inactivated bacterial vector carrying the K39 antigen,as well as the purified antigen can induce a long-lasting immune response in immunized mice,predominantly favouring a Th2 profile response.