Effect of Aluminum Hydroxide Adjuvant on the Immunogenicity of the 2009 Pandemic Influenza A/H1N1 Vaccine:Multi-level Modeling of Data with Repeated Measures

Objective To evaluate the effect of the aluminum hydroxide （Al-OH） adjuvant on the 2009 pandemic influenza A/H1N1 （pH1N1） vaccine. Methods In a multicenter, double-blind, randomized, placebo-controlled trial, participants received two doses of split-virion formulation containing 15 ug hemagglutinin antigen, with or without aluminum hydroxide （N-OH）. We classified the participants into six age categories （〉61 years, 41-60 years, 19-40 years, 13-18 years, 8-12 years, and 3-7 years） and obtained four blood samples from each participant on days 0, 21, 35, and 42 following the first dose of immunization. We assessed vaccine immunogenicity by measuring the geometric mean titer （GMT） of hemagglutination inhibiting antibody. We used a two-level model to evaluate the fixed effect of aluminum Al-OH and other factors, accounting for repeated measures. Results The predictions of repeated measurement on GMTs of formulations with or without Al-OH, were 80.35 and 112.72, respectively. Al-OH significantly reduced immunogenicity after controlling for time post immunization, age-group and gender. Conclusion The Al-OH adjuvant does not increase but actually reduces the immunogenicity of the split-virion pH1N1 vaccine.

Developments of Subunit and VLP Vaccines Against Influenza A Virus

Influenza virus is a continuous and severe global threat to mankind. The continuously re-emerging disease gives rise to thousands of deaths and enormous economic losses each year, which emphasizes the urgency and necessity to develop high-quality influenza vaccines in a safer, more efficient and economic way. The influenza subunit and VLP vaccines, taking the advantage of recombinant DNA technologies and expression system platforms, can be produced in such an ideal way. This review summarized the recent advancements in the research and development of influenza subunit and VLP vaccines based on the recombinant expression of hemagglutinin antigen (HA), neuraminidase antigen (NA), Matrix 2 protein (M2) and nucleocapsid protein (NP). It would help to get insight into the current stage of influenza vaccines, and suggest the future design and development of novel influenza vaccines.

Immunological Effect of Subunit Influenza Vaccine Entrapped by Liposomes

Objective To elevate the immunological effect of subunit influenza vaccine in infants and aged people （over 60） using liposomal adjuvant in the context of its relatively low immunity and to investigate the relation between vaccine antigens and liposomal characteristics. Methods Several formulations of liposomal subunit influenza vaccine were prepared. Their relevant characteristics were investigated to optimize the preparation method. Antisera obtained from immunizinged mice were used to evaluate the antibody titers of various samples by HI and EL1SA. Results Liposomal trivalent influenza vaccine prepared by film evaporation in combinedation with freeze-drying significantly increased its immunological effect in SPF Balb/e mice. Liposomal vaccine stimulated the antibody titer of H3N2, H1N1, and B much stronger than conventional influenza vaccine. As a result, liposomal vaccine （mean size： 4.5-5.5 pm, entrapment efficiency： 30%-40%） significantly increased the immunological effect of subunit influenza vaccine. Conclusion The immune effect of liposomal vaccine depends on different antigens, and enhanced immunity is not positively correlated with the mean size of liposome or its entrapped efficiency.

Immunogenic and Protective Properties of the First Kazakhstan Vaccine against Pandemic Influenza А(Н1N1) pdm09 in Ferrets

This paper presents the results of a pre-clinical study of the immunogenicity and efficacy of an egg-derived, inactivated, whole-virion adjuvanted vaccine （Refluvac） on ferret models. For this purpose, groups of eight ferrets （6 to 7 months old） were injected with 0.5 mL of vaccine specimens containing 3.75, 7.5 or 15.0 μg of virus hemagglutinin. Administration was intramuscular and given either as a single dose or as two doses 14 days apart. All vaccine specimens manifested immunogenicity in ferrets for single （HI titer, from 51 ± 7 to 160 ± 23） and double （HI titer, from 697± 120 to 829 ± 117） administrations. To assess the protective effects of the vaccine, ferrets from the vaccinated and control groups were infected intranasally with pandemic virus A/California/7/09 （H1N1） pdm09 at a dose of 106 106/0.5 mL. Fourteen days post-infection, the ferrets inoculated with single or double vaccines containing 3.75, 7.5 or 15.0 ~g of hemagglutinin per dose showed no signs of influenza infection, weight loss, or body temperature rise, and no premature deaths occurred. The number of vaccinated ferrets shedding the virus via the upper airway, as well as the amount of virus shed after infection, was significantly reduced in comparison with animals from the control group. Based on our results, we suggest that a single vaccination at a dose of 3.75 or 7.5 μg hemagglutinin be used for Phase I clinical trials.

Safety Observation Study on Haemophilus Influenza Type B Conjugate Vaccines Injected at Different Sites in Chinese Infants

In the present study, the safety of Hoemophilus influenza type b conjugate vaccines inoculated in the upper arm deltoid and vastus lateralis muscle was evaluated. 680 infants aged 2-5 months and 6-12 months were selected to be the research subjects in whom the Hib conjugate vaccines were inoculated by injection in the upper arm deltoid and vastus lateralis muscle, respectively. The safety analysis indicated that there were no statistic differences in the incidence rates of adverse reactions when the Hib conjugate vaccines were inoculated at different sites. So we concluded that the safety of inoculation injection of Hib conjugate vaccines in vastus lateralis muscle was the same as that inoculated in the upper arm deltoid.

Effectiveness and safety of COVID-19 vaccines in patients with oncological diseases:State-of-the-art

Although the coronavirus disease 2019(COVID-19)pandemic was declared to be no longer“a public health emergency of international concern”with its wide range of clinical manifestations and late complications,severe acute respiratory syndrome coronavirus 2 infection proved to be a serious threat,especially to the elderly and patients with comorbidities.Patients with oncologic diseases are vulnerable to severe infection and death.Indeed,patients with oncohematological diseases have a higher risk of severe COVID-19 and impaired post-vaccination immunity.Unfortunately,cancer patients are usually excluded from vaccine trials and investigations of post-vaccinal immune responses and the effectiveness of the vaccines.We aimed to elucidate to what extent patients with cancer are at increased risk of developing severe COVID-19 and what is their overall case fatality rate.We also present the current concept and evidence on the effectiveness and safety of COVID-19 vaccines,including boosters,in oncology patients.In conclusion,despite the considerably higher mortality in the cancer patient group than the general population,countries with high vaccination rates have demonstrated trends toward improved survival of cancer patients early and late in the pandemic.

Safety and Antibody Responses to Aerosolized MMR II Vaccine in Adults: An Exploratory Study

Background: There have been no reported studies involving aerosol immunization with 2 of the 3 components of MMR II vaccine—Attenuvax measles vaccine and Jeryl-Lyn mumps vaccine. Objective: To evaluate the safety and antibody responses to aerosolized Attenuvax measles strain, Jeryl Lynn mumps strain and RA 27/3 rubella component of an MMR vaccine in adults, before assessing the booster administration of this vaccine in children. Methods: A pilot study to evaluate safety and antibody responses of MMR II (Merch Sharp & Dhome Corp., Whitehouse Station, NJ 08889, USA) components administered by aerosol was carried out in 27 healthy adults of 21 to 38 years of age. All participants were followed-up during 28 days following immunization for detection of clinical adverse events. Immune response was evaluated by plaque reduction neutralization test for measles, and commercial ELISA kits for rubella and mumps. Results: Only mild clinical adverse events were noted. Despite high levels of baseline seropositivity to all vaccine components, seroresponses to measles, rubella and mumps occurred in 44%, 15% and 41%, respectively. Conclusions: These outcomes compare favorably with earlier studies of other MMR vaccines given by aerosol. Further evaluations on safety and booster immune response should be performed in children.

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.

A Combination Vaccine against Encephalomyocarditis Virus and Porcine Circovirus Type 2 Induces Protective Immune Response in Pigs

Encephalomyocarditis virus (EMCV) and porcine circovirus type 2 (PCV2) are common causative agents with high infection rate in pig farms, thus a combined vaccine against both EMCV and PCV2 is highly desirable. In the present study, we developed an oil-adjuvant combination vaccine candidate comprising of inactivated EMCV and PCV2, and evaluated the safety and immunogenicity in mice and swine. The combination vaccine was found to elicit serum antibodies and had strong neutralization activity, more importantly, passive immunization with the combined vaccine protected swine against either EMCV or PCV2 lethal infections, whereas the monovalent vaccine only prevent the one of two virus challenge. Our results demonstrated the combined vaccine was safe and induced protective immune response in mice and swine as evident from sero-conservation as well as challenge studies in swine, indicating that component vaccines did not interfere with the immunogenicity of each other.

Safety and tolerability of intradermal influenza vaccination in patients with cardiovascular disease

Background It is well-established that influenza vaccination reduces adverse cardiovascular outcomes in patients with cardiovascular diseases （CVD）, however, the vaccine coverage rate in most countries remains low. The concern about the local adverse effects of intramus-cular injection, particularly in CVD patients receiving antithrombotic therapy, is one of the important impediments. This study was con-ducted to assess the safety, side effects and tolerability of intradermal influenza vaccine in CVD patients. Methods This was an observa-tional study in adult CVD patients who had undergone vaccination against seasonal influenza by intradermal vaccination between May 16th and May 30th, 2012 at Maharaj Nakorn Chiang Mai Hospital. The medical history, patients＇ acceptability and adverse effects were collected using a written questionnaire completed by the patient immediately following vaccination and by a telephone survey eight days later. Results Among 169 patients, 52.1%were women and the mean age was 63 ＆#177; 12 years. Coronary artery disease, valvular heart disease and dilated cardiomyopathy were present in 121 （71.6%）, 40 （23.7%） and 8 （4.7%）, respectively. Antithrombotics were used in 89.3%. After vaccination, the pain score was 0, 1 or 2 （out of 10） in 44.4%, 15.1%, and 27.6%of the patients, respectively. Eight days after vaccination, the common adverse reactions were itching 19 （11.9%）, swelling 9 （5.7%） and fatigue （4.7%）. No hematoma or bruising was reported. Conclusions The intradermal influenza vaccination is safe and well tolerates with high rates of satisfaction in CVD patients. This technique should be useful in expanding influenza vaccine coverage.

Intramuscular vaccine administrations including the adoption of"Zeta-track technique"&"without aspiration slow injection technique"(ZTT&WASiT):a prospective review

Objective:To review the current literature on the practice of intramuscular injections(IMIs),focusing on immunizations.Methods:The present study comprises 2 reviews,characterized by high-quality evidence,per taining to the deployment of the slow injection technique without aspiration(referred to in this paper as the without-aspiration slow injection technique[WASi T])and combined with the Zeta-track technique(ZTT).The literature review is oriented toward the analysis of 2 features associated with IMIs techniques:safety and pain,integrating new evidence on vaccinee positioning for each muscle site and general relaxation techniques in the multi-parametric analysis.Results:The rigorous and in-depth reviews in the current study reveal the usefulness of including,among the international guidelines for via intramuscular immunizations,the adoption of WASi T only for compliant vaccinees,and in combination with all validated techniques for IMIs,and the use of ZTT limitedly if specific well-developed muscles are indicated.All the technique's limitations are exposed.Conclusions:Future research directions are presented by including the author's study designs to provide indirect evidence for the validity of the rationale of the slow injection technique using scientific methods,and for the conduction of future randomized controlled trials(RCTs)focused on revisiting the adoption of ZTT in a dynamic and integrated immunizations protocol in anterolateral thigh(ALT),ventrogluteal(VG),and also in the deltoid muscle,in the specific cases analyzed.

Safety,immunogenicity,and cross-species protection of a plasmid DNA encoding Plasmodium falciparum SERA5 polypeptide,microbial epitopes and chemokine genes in mice and olive baboons

Incorporation of biomolecular epitopes to malarial antigens should be explored in the development of straintranscending malarial vaccines.The present study sought to determine safety,immunogenicity and cross-species efficacy of Plasmodium falciparum serine repeat antigen 5 polypeptide co-expressed with epitopes of BacilleCalmette Guerin（BCG）,tetanus toxoid（TT） and a chemokine gene.Olive baboons and BALB/c mice were randomly assigned into vaccine and control groups.The vaccine group animals were primed and boosted twice with pIRES plasmids encoding the SERA5 ＋ BCG ＋ TT alone,or with either CCL5 or CCL20 and the control group with pIRES plasmid vector backbone.Mice and baboons were challenged with P.berghei ANKA and P.knowlesi H strain parasites,respectively.Safety was determined by observing for injection sites reactogenicities,hematology and clinical chemistry.Parasitaemia and survivorship profiles were used to determine cross-species efficacy,and T cell phenotypes,Th1-,Th2-type,T-regulatory immune responses and antibody responses were assessed to determine vaccine immunogenicity.The pSeBCGTT plasmid DNA vaccines were safe and induced Thl-,Th2-type,and Tregulatory responses vaccinated animals showed enhanced CD4~＋（P〈0.01）,CD 8~＋ T cells（P〈 0.001） activation and IgG anti-SE36 antibodies responses（P〈 0.001） at week 4 and 8 post vaccination compared to the control group.Vaccinated mice had a 31.45-68.69%cumulative parasite load reduction and 60%suppression in baboons（P〈0.05）and enhanced survivorship（P〈 0.001） with no clinical signs of malaria compared to the control group.The results showed that the vaccines were safe,immunogenic and conferred partial cross-species protection.

Immunogenicity and safety of a new inactivated hepatitis A vaccine in young adults: a comparative study

To evaluate the immunogenicity, safety, and dosage of a new inactivated hepatitis A vaccine administered to young adults Methods One hundred and four normal adult volunteers, seronegative for hepatitis A virus and hepatitis B surface antigen, were randomly assigned to one of three groups The high dose group received a primary dose of 1000 units of the new vaccine, the low dose group received a primary dose of 500 units of the same vaccine, and the Havrix group received a primary dose of 1440 enzyme linked immunosorbent assay units of Havrix, a licensed inactivated hepatitis A vaccine All groups received a booster dose of the same vaccine 6 months after the primary dose Local and systemic adverse reactions, seroconversion rates, and geometric mean titers of hepatitis A virus antibodies were measured in all three groups Results Local and systemic reaction types and rates were similar in all three groups after primary and booster doses, although local reactions were more frequent in the Havrix group following the primary dose No serious adverse reactions occurred One month after the primary dose, the seroconversion rate was 87 5% in the high dose group, 70 0% in the low dose group, and 50.0% in the Havrix group ( P =0.001, versus the high dose group) At month 6 (before administration of the booster dose), seroconversion rates were 96 9% in the high dose group, 65 0% in the low dose group ( P =0 0029), and 68 8% in the Havrix group ( P =0 007) All subjects in all groups seroconverted by one month after receipt of the booster dose Geometric mean titers were similar in all three groups at month 1, but were higher in the high dose group (264 mIU/ml) than those in the Havrix group (135 mIU/ml) at month 6 ( P =0 0013) One month after the booster dose, geometric mean titers in the high dose group (2747 mIU/ml) were higher than those in the low dose group (1657 mIU/ml) ( P =0 0223) or in the Havrix group (1316 mIU/ml) ( P =0 01) Conclusions This new inactivated hepatitis A vaccine is immunogenic and safe; two doses of either 500 or 1000 units can induce hepatitis A virus antibodies well above the protection level

Immunogenicity and safety of a severe acute respiratory syndrome coronavirus 2 inactivated vaccine in healthy adults: randomized, double-blind, and placebo-controlled phase 1 and phase 2 clinical trials

Background:The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)call for urgent development of effective and safe vaccines.We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine,KCONVAC,in healthy adults.Methods:Phase 1 and phase 2 randomized,double-blind,and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years.The participants in the phase 1 trial were randomized to receive two doses,one each on Days 0 and 14,of either KCONVAC(5 or 10 mg/dose)or placebo.The participants in the phase 2 trial were randomized to receive either KCONVAC(at 5 or 10 mg/dose)or placebo on Days 0 and 14(0/14 regimen)or Days 0 and 28(0/28 regimen).In the phase 1 trial,the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose.In the phase 2 trial,the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose.Results:Inthe phase1 trial,60 participantswere enrolled andreceived at least one dose of 5-mgvaccine(n=24),10-mgvaccine(n=24),or placebo(n=12).In the phase 2 trial,500 participantswere enrolled and received at least one dose of 5-mg vaccine(n=100 for 0/14 or 0/28 regimens),10-mg vaccine(n=100 for each regimen),or placebo(n=50 for each regimen).In the phase 1 trial,13(54%),11(46%),and seven(7/12)participants reported at least one adverse event(AE)after receiving 5-,10-mg vaccine,or placebo,respectively.In the phase 2 trial,16(16%),19(19%),and nine(18%)0/14-regimen participants reported at least oneAEafter receiving 5-,10-mg vaccine,or placebo,respectively.Similar AE incidences were observed in the three 0/28-regimen treatment groups.No AEs with an intensity of grade 3+were reported,expect for one vaccine-unrelated seriousAE(foot fracture)reported in the phase 1 trial.KCONVACinduced significant antibody responses;0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses.Conclusions:Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults.These results support testing 5-mg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial.Trial Registration:http://www.chictr.org.cn/index.aspx(No.ChiCTR2000038804,http://www.chictr.org.cn/showproj.aspx?proj=62350;No.ChiCTR2000039462,http://www.chictr.org.cn/showproj.aspx?proj=63353).

Immunogenicity,effectiveness,and safety of COVID‑19 vaccines among children and adolescents aged 2–18 years:an updated systematic review and meta‑analysis

Background During the coronavirus disease 2019(COVID-19)pandemic,there is an urgent need for safe and effective COVID-19 vaccines to protect children and adolescents.This study aims to provide scientific evidence and recommendations for the application of COVID-19 vaccines in children and adolescents by analyzing the latest studies.Methods We systematically searched MEDLINE(accessed through PubMed),Embase,and Web of Science from January 1,2020,to October 8,2022.Eligible clinical trials,cohort studies,case‒control studies,and cross-sectional studies with extractable data were included in immunogenicity,effectiveness,and safety analyses.According to the heterogeneity,we chose a fixed-effect model(when I2≤50)or a random-effects model(when I2>50)to pool effect values.Results A total of 88 articles were included.The seroconversion rates after the first,second,and third doses of the vaccines were 86.10%,96.52%,and 99.87%,respectively.After the first and second doses,vaccine effectiveness(VE)against severe acute respiratory syndrome coronavirus 2 infection was 42.87%[95%confidence interval(CI)=27.09%–58.65%]and 63.33%(95%CI=52.09%–74.56%),respectively.After the first and second doses,VE against COVID-19 was 60.65%(95%CI=44.80%–76.50%)and 75.77%(95%CI=63.99%–87.56%),respectively.VE against hospitalization due to COVID-19 after the first and second doses was 72.74%(95%CI=51.48%–94.01%)and 82.78%(95%CI=75.78%–89.78%),respectively.The most common adverse events were injection site pain,fatigue/asthenia/tiredness,headache,myalgia/muscle pain,and chills.The incidence rate of myocarditis or pericarditis was 2.42/100,000 people.In addition,the subgroup analysis showed that children aged≤5 years had the lowest incidence of adverse events,and the incidence rate of adverse events was higher for mRNA vaccines than for inactivated vaccines.Conclusions COVID-19 vaccines have good immunogenicity,effectiveness,and safety among children and adolescents.We recommend that children and adolescents be vaccinated as soon as possible to protect them and slow the spread of COVID-19.

Immunogenicity and safety of a recombinant fusion protein vaccine(V-01)against coronavirus disease 2019 in healthy adults:a randomized,double-blind,placebo-controlled,phaseⅡtrial

Background:Innovative coronavirus disease 2019(COVID-19)vaccines,with elevated global manufacturing capacity,enhanced safety and efficacy,simplified dosing regimens,and distribution that is less cold chain-dependent,are still global imperatives for tackling the ongoing pandemic.A previous phase I trial indicated that the recombinant COVID-19 vaccine(V-01),which contains a fusion protein(IFN-PADRE-RBD-Fc dimer)as its antigen,is safe and well tolerated,capable of inducing rapid and robust immune responses,and warranted further testing in additional clinical trials.Herein,we aimed to assess the immunogenicity and safety of V-01,providing rationales of appropriate dose regimen for further efficacy study.Methods:A randomized,double-blind,placebo-controlled phaseⅡclinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention(Guangdong,China)in March 2021.Both younger(n=440;18–59 years of age)and older(n=440;≥60 years of age)adult participants in this trial were sequentially recruited into two distinct groups:two-dose regimen group in which participants were randomized either to follow a 10 or 25 mg of V-01 or placebo given intramuscularly 21 days apart(allocation ratio,3:3:1,n=120,120,40 for each regimen,respectively),or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 mg of V-01 or placebo(allocation ratio,3:1,n=120,40,respectively).The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2,and specific binding antibodies to the receptor binding domain(RBD).The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events(AEs)within 30 days after full immunization.Results:V-01 provoked substantial immune responses in the two-dose group,achieving encouragingly high titers of neutralizing antibody and anti-RBDimmunoglobulin,which peaked at day 35(161.9[95%confidence interval[CI]:133.3–196.7]and 149.3[95%CI:123.9–179.9]in 10 and 25 mg V-01 group of younger adults,respectively;111.6[95%CI:89.6–139.1]and 111.1[95%CI:89.2–138.4]in 10 and 25 mg V-01 group of older adults,respectively),and remained high at day 49 after a day-21 second dose;these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients(53.6,95%CI:31.3–91.7).Our preliminary data showthat V-01 is safe andwell tolerated,with reactogenicity predominantly being absent or mild in severity and only one vaccinerelated grade 3 or worse AE being observed within 30 days.The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group:with AEs percentages of 19.2%,25.8%,17.5%in older adults vs.34.2%,23.3%,26.7%in younger adults at the 10,25 mg V-01 two-dose group,and 50 mg V-01 one-dose group,respectively.Conclusions:The vaccine candidate V-01 appears to be safe and immunogenic.The preliminary findings support the advancement of the two-dose,10 mg V-01 regimen to a phaseⅢtrial for a large-scale population-based evaluation of safety and efficacy.

Safety and Immunogenicity of SARS-CoV-2 Vaccines in People Living With HIV:A Systematic Review and Meta-analysis of Real-World Studies

The safety and immunogenicity of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)vaccines in people living with HIV(PLWH)in real-world studies remain controversial.Thus,we conducted a comprehensive systematic review and meta-analysis to address this issue.Data search were conducted from PubMed,Web of Science and EMBASE.Adverse events following vaccination,the risk ratio(RR)of SARS-CoV-2–specific IgG seroconversion and the level of anti–SARS-CoV-2 neutralizing antibodies were compared between the PLWH group and a healthy control group.A total of 10,582 PLWH from 22 studies were included.In our analysis,the incidence of local or systemic adverse events after the first SARS-CoV-2 vaccine dose was not statistically different between PLWH and healthy controls.However,there was a statistical difference after the second dose(RR,0.83;95%CI,0.71–0.98).The seroconversion rate of SARS-CoV-2 IgGantibodies in PLWH was significantly lower than that in the healthy control group(RR,0.94;95%CI,0.89–0.98;I2=80%,P<0.01).The anti–SARS-CoV-2 neutralizing antibody titers in PLWH after full immunization were also significantly lower than those in the healthy control group(RR,0.91;95%CI,0.85–0.98;I2=81%,P<0.01).The safety and tolerance of COVID-19 vaccines in PLWHare acceptable.However,their immunogenicitymay be impaired to a certain extent,characterized by a lower IgGseroconversion rate and neutralizing antibody titers compared with healthy individuals.These findings should provide guidance for optimizing future COVID-19 vaccination strategies among PLWH.

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%.

Structural vaccinology: structure-based design of influenza A virus hemagglutinin subtype-specific subunit vaccines

There is a great need for new vaccine development against influenza A viruses due to the drawbacks of traditional vaccines that are mainly prepared using embryonated eggs.The main component of the current split influenza A virus vaccine is viral hemagglutinin(HA)which induces a strong antibody-mediated immune response.To develop a modern vaccine against influenza A viruses,the current research has been focused on the universal vaccines targeting viral M2,NP and HA proteins.Crystallographic studies have shown that HA forms a trimer embedded on the viral envelope surface,and each monomer consists of a globular head(HA1)and a“rod-like”stalk region(HA2),the latter being more conserved among different HA subtypes and being the primary target for universal vaccines.In this study,we rationally designed the HA head based on the crystal structure of the 2009-pandemic influenza A(H1N1)virus HA as a model,tested its immunogenicity in mice,solved its crystal structure and further examined its immunological characteristics.The results show that the HA globular head can be easily prepared by in vitro refolding in an E.coli expression system,which maintains its intact structure and allows for the stimulation of a strong immune response.Together with recent reports on some similar HA globular head preparations we conclude that structure-based rational design of the HA globular head can be used for subtype-specific vaccines against influenza viruses.

Immunogenicity and protective immunity against otitis media caused by pneumococcus in mice of Hib conjugate vaccine with PsaA protein carrier

This study evaluated the immunogenicity and protective immunity of a Hemophilus influenzae b （Hib） polysaccharide conjugate vaccine with the pneumococcal surface adhesin A （PsaA） protein carrier in young mice. The Hib polysaccharide was conjugated with the rPsaA protein carrier, which was produced using recombinant DNA technology. A total of 15 young mice aged 3 weeks to 5 weeks were immunized with the conjugate vaccine, and another 15 young mice of the same age were immunized with the licensed Hib-tetanus toxoid （TT） vaccine. Furthermore, the third group of 15 young mice was inoculated with phosphate buffer saline as control. The immunized mice were inoculated with pneumococcus in the middle ear. Results showed that IgG antibody responses against both the PsaA protein and Hib polysaccharide were observed in the Hib-PsaA group. However, no statistical difference was observed in the titer of ｜gG against the Hib polysaccharide between Hib-PsaA and Hib-TT groups. The elimination rate of pneumococcus and the inflammation of the middle ear showed the effectiveness of protective immunity against otitis media caused by pneumococcus. Our results suggest that the Hib polysaccharide can be successfully conjugated with rPsaA via amide condensation. This new Hib-PsaA conjugate vaccine can induce both anti-PsaA and anti-Hib immune responses in young mice and elicit effective protection against acute otitis media caused by pneumococcus.