Reactivation of latent varicella-zoster virus (VZV) causes herpes zoster, which can further progress to persistent postherpetic neuralgia in a subset of patients. Rational adjuvant selection is critical for the development of recombinant VZV glycoprotein E (gE) subunit vaccines. In this study, we systematically evaluated the immunomodulatory properties of six adjuvants formulated with recombinant VZV gE in a mouse model. Multi-dimensional analyses, including innate and adaptive immunity, transcriptomics, and B-cell receptor (BCR) repertoire profiling, revealed that distinct adjuvants shape adaptive immune responses through divergent innate immune activation patterns. Traditional aluminum hydroxide and MF59 mainly induced Th2-biased humoral immunity but showed limited cellular immune activation. As TLR agonists, Poly(I:C) displayed a Th2-skewed profile with partial Th1 tendencies and exhibited oligoclonal B-cell expansion, whereas CpG 1018 potently promoted Th1 polarization and cytotoxic T-cell responses. Lipid nanoparticle (LNP) formulations drove chemokine-dependent inflammatory recruitment and facilitated dendritic cell maturation and humoral immune programming. Notably, KA101, a liposomal adjuvant containing MPL and QS-21, exhibited unique synergistic effects by inducing early IFN-γ production and simultaneously eliciting robust cellular immunity and high-titer neutralizing antibodies. Moreover, KA101 enhanced germinal center reactions, diversified the B-cell repertoire, and supported the establishment of long-term immune memory. Collectively, these findings provide mechanistic insights into adjuvant-antigen interactions and establish a rational framework for developing next-generation herpes zoster subunit vaccines with potent cellular and humoral immunogenicity and durable immune memory.

Developing potent adjuvants is critical for enhancing vaccine efficacy, particularly for subunit antigens. Background/Objectives: This study evaluates a novel composite adjuvant system combining liposomal QS-21 and CpG ODNs to enhance vaccine-induced immunogenicity, particularly Th1-type cellular immunity. Methods: To mitigate QS-21’s hemolytic toxicity and ensure precision delivery, a stable liposomal formulation was developed. Mice models were established using varicella-zoster virus (VZV) glycoprotein E (gE) or ovalbumin (OVA) as antigens to evaluate humoral and cellular immune responses. Results: Immunization with gE protein formulated with this novel adjuvant synergistically triggered robust immune responses, outperforming single adjuvants and the combination of QS-21/MPL. Across broad dose ranges, it induced higher Th1-type cellular immunity and comparable humoral immunity relative to AS01B. Mechanistic studies revealed that the adjuvant significantly enhances the recruitment of dendritic cells (DCs), monocytes, and neutrophils to draining lymph nodes (dLNs) while upregulating co-stimulatory molecules CD40 and CD86 on DCs. Furthermore, the formulation triggered robust, transient increases in Th1-associated cytokines (IFN-γ, IL-12) and chemokines (CXCL9, CXCL10) across the injection site, serum, and dLNs. Conclusions: These findings indicate that the liposomal QS-21 and CpG ODNs system is a highly effective platform for promoting robust Th1-biased immunity, offering a promising adjuvant candidate and a solid experimental foundation for developing next-generation vaccines requiring potent cellular immunity.

In previously completed Phase 1 and 2 clinical trials, a recombinant gE-Fc fusion protein subunit vaccine adjuvanted with aluminum hydroxide (called LZ901) demonstrated favorable safety profiles and elicited robust immune responses. This randomized, placebo-controlled, double-blind, phase 3 trial (ChiCTR2300076253) evaluated the efficacy and safety of LZ901 in adults ≥40 years. 26,018 participants received either two intramuscular doses of LZ901 (30-day interval; n = 13,010) or a placebo (30-day interval; n = 13,008). The primary objective was to assess herpes zoster risk within 12-months after LZ901 vaccination. During the follow-up period, 15 LZ901 recipients and 178 placebo recipients were confirmed positive for herpes zoster. Overall vaccine efficacy against herpes zoster was 91.6% (95% confidence interval, 86.3 to 95.3; p < 0.001); efficacy was higher in participants aged 40-69 years [93.9% (95% confidence interval, 89.1 to 97.0; p < 0.001)] than in participants aged ≥70 years [66.9% (95% confidence interval, 14.6 to 89.2; p = 0.016)]. Post-herpetic neuralgia occurred in 1 of 15 herpes zoster cases in the LZ901 group and in 24 of 187 herpes zoster cases in the placebo group, corresponding to a vaccine efficacy of 95.5% (95% confidence interval, 63.9 to 99.93; p < 0.001) against post-herpetic neuralgia. LZ901 recipients had more injection-site and systemic reactions within 7 days of vaccination compared to the placebo group; grade 3 reactions were comparably low in both the LZ901 and placebo groups (0.3% versus 0.4%, respectively). No serious adverse events or safety concerns associated with LZ901 were noted. LZ901 reduces the risk of herpes zoster in adults who were 40 years of age or older in 12 months, with a favorable safety profile. Jingxin Li and colleagues report a randomized, placebo-controlled, phase 3 trial to evaluate the efficacy and safety of LZ901, recombinant gE-Fc fusion protein adjuvanted with aluminium hydroxide, against herpes zoster. They report that the vaccine reduces the risk of viral infection and has favorable safety profiles.

The licensed adjuvanted recombinant glycoprotein E (gE) subunit vaccine (HZ/su) is highly effective against herpes zoster (HZ). This randomised, active-controlled, non-inferiority trial (ChiCTR2300079076) compared the immunogenicity and safety of a novel gE-Fc fusion protein vaccine candidate (LZ901) with HZ/su in 300 healthy adults aged ≥50 years without prior HZ vaccination in Wuxi, China. Participants received either two doses of LZ901 (30-day interval; n = 151) or HZ/su (60-day interval; n = 149). The primary outcomes was the proportion of participants with simultaneous positive responses to two or more cytokines (IFN-γ, IL-2, TNF-α, or CD40L) 30 days after the second dose (referred to as gE-specific CD42+/CD82+ T-cell responses). LZ901 demonstrated non-inferiority to HZ/su (margin > -10%) for both CD4+ and CD8+ T-cell responses. Significantly higher response rates were observed with LZ901 for CD42 + T-cell responses (83.0% [117/141] vs 58.1% [79/136]; p < 0.0001) and CD82 + T-cell responses (46.8% [66/141] vs 8.8% [12/136]; p < 0.0001). Adverse reactions were markedly lower with LZ901 (41.1% [62/151] vs 87.9% [131/149]; p < 0.0001), including grade 3 events (0.7% [1/151] vs 6.0% [9/149]). LZ901 induced superior cellular immunogenicity and exhibited a better safety profile than HZ/su in adults ≥50 years, supporting its potential as a promising HZ prevention candidate vaccine.

IntroductionReactivation of the varicella-zoster virus (VZV) results in herpes zoster (HZ), which can lead to complications such as postherpetic neuralgia. The commercially available HZ subunit adjuvanted vaccine, Shingrix®, offers significant protection against HZ in older adults. However, the adjuvant system of this vaccine has limitations that necessitate the development of alternative adjuvant systems.MethodsIn this study, we established a novel adjuvant system, BK-02, composed of both the Toll-like receptor 9 (TLR9) agonist BK-02C (CpG2006) and a squalene-based oil-in-water emulsion, BK-02M (MF59), using ELISA, ELISpot, and flow cytometry analyses. ResultsOur results showed that when combined with glycoprotein E (gE), the active ingredient of a recombinant HZ vaccine, the BK-02 adjuvant system elicited significantly higher gE-specific IFN-γ+ T-cell responses (486 SFU/10⁶ cells, 121-fold increase vs gE alone) and IgG antibody titers (Lg titers 5.2 vs 3.4 for gE alone). The optimal dose (5 μg gE + 30 μg BK-02C + 1× BK-02M) for inducing gE protein-specific cellular immunity was determined in mice. This corresponded to a clinical dose of “50 μg gE + 300/500 μg BK-02C + 0.5 mL BK-02M.” Additionally, pilot-scale samples of the recombinant HZ vaccine demonstrated enhanced gE-specific CD4+ and CD8+ T-cell immune responses, compared to Shingrix®. Moreover, the gE/BK-02 adjuvant system induced a Th1-regulated mixed immune response, enabling robust cellular and humoral immunity. DiscussionThese findings indicated that the BK-02 adjuvant system is a promising adjuvant candidate for the current HZ subunit vaccines.

Varicella-zoster virus (VZV) is a human neurotropic herpesvirus. The primary infection with VZV causes chickenpox and establishes latency in sensory and dorsal root ganglia. Viral reactivation leads to herpes zoster (HZ), which is accompanied by complications such as postherpetic neuralgia (PHN), causing a significant disease burden. At present, vaccination is the most effective preventive measure. We developed a recombinant zoster vaccine, gE/BFA01, which comprises truncated VZV glycoprotein E and the liposome-based adjuvant BFA01 (containing MPL and QS-21). In this study, we evaluated the recombinant zoster vaccine’s immunogenicity in a live attenuated VZV-primed C57BL/6N mouse model and explored the mechanism of action of the BFA01 adjuvant. The results indicate that the gE/BFA01 vaccine induces superior antibody responses and stronger cellular immune responses compared with gE with aluminum hydroxide. Furthermore, gE/BFA01 showed comparable immunogenicity to the licensed vaccine Shingrix. Mechanistic investigations revealed that the BFA01 adjuvant can enhance the recruitment of innate immune cells at the injection site, increase the expression of DCs surface maturation markers, and activate multiple inflammatory signaling pathways in lymph nodes. Collectively, these findings indicate that gE/BFA01 can induce potent humoral and cellular responses, supporting its further development as a high-efficiency vaccine candidate.

The continuous evolution and mutation of SARS-CoV-2 have highlighted the need for more effective vaccines. In this study, CpG, MF59-like, and Alum adjuvant Delta strain inactivated SARS-CoV-2 vaccines were prepared, and the immunogenicity of these vaccines in mice was evaluated. The Delta + MF59-like vaccine group produced the highest levels of S- and RBD-binding antibodies and live Delta virus neutralization levels after one shot of immunization, while mice in the Delta + Alum vaccine group had the highest levels of these antibodies after two doses, and the Delta + MF59-like and Delta + Alum vaccine groups produced high levels of cross-neutralization antibodies against prototype, Beta, and Gamma strain SARS-CoV-2 viruses. There was no significant decrease in neutralizing antibody levels in any vaccine group during the observation period. CpG, MF59-like, and Alum adjuvant Delta strain inactivated SARS-CoV-2 vaccines excited different antibody subtypes compared with unadjuvanted vaccines; the Delta + CpG vaccine group had a higher proportion of IgG2b antibodies, indicating bias towards Th1 immunity. The proportions of IgG1 and IgG2b in the Delta + MF59-like vaccine group were similar to those of the unadjuvanted vaccine. However, the Delta + Alum vaccine group had a higher proportion of IgG1 antibodies, indicating bias towards Th2 immunity. Antigen-specific cytokine secretion CD4/8+ T cells were analyzed. In conclusion, the results of this study show differences in the immune efficacy of CpG, MF59-like, and Alum adjuvant Delta strain inactivated SARS-CoV-2 vaccines in mice, which have significant implications for the selection strategy for vaccine adjuvants.

Herpes zoster (HZ) is an infectious disease caused by the reactivation of varicella zoster virus (VZV), with 68% of cases occurring in adults over 50 years of age. HZ/su (Shingrix®) was approved by the Food and Drug Administration in 2017 for the prevention of HZ in individuals ≥ 50 years of age and showed very good protection from HZ. However, due to the use of the adjuvant AS01B, adverse reactions caused by Shingrix are a concern. Aluminum hydroxide is the most commonly used adjuvant and is widely used in a variety of vaccines. We developed a recombinant zoster vaccine (code: LZ901) consisting of a tetramer of VZV glycoprotein E (gE) and a human Fc fusion protein expressed in CHO cells, an immune complex-like molecule that can be adsorbed with an aluminum hydroxide adjuvant. We compared the immunogenicity of LZ901 with that of HZ/su in BALB/c mice. The results showed that LZ901 induced levels of gE-specific IgG antibodies comparable to those induced by HZ/su, and the results of FAMA titers further demonstrated their similar neutralizing antibody abilities. Most importantly, LZ901 induced higher levels of cell-mediated immunity (CMI) (which plays a decisive role in the efficacy of zoster vaccines) than HZ/su in BALB/c mice. The numbers of cytokine-producing T cells in LZ901-vaccinated mice were significantly greater than those in v-vaccinated mice, and the proportions of CD4+ and CD8+ T cells producing at least two types of cytokines in LZ901-vaccinated mice were significantly greater than those in HZ/su-vaccinated mice.

目的 制备重组严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)蛋白疫苗抗原含量通用检测试剂盒,并进行验证.方法 选用中国食品药品检定研究院(简称中检院)制备的羊抗S蛋白多克隆抗体作为包被抗体,从4株单克隆抗体(14C8、15F9、17A7和20D8)中筛选出1株具有受体结合域(receptor-binding domain,RBD)结合活性高,且广谱抗主要突变株的单克隆抗体作为酶标抗体(用HRP标记),制备重组SARS-CoV-2疫苗抗原含量的双抗体夹心ELISA法通用检测试剂盒,并采用棋盘滴定法对包被抗体稀释度(1∶ 125～1∶ 4 000)和酶标抗体稀释度(1 ∶250～1∶ 32000)进行优化.验证试剂盒的专属性、线性范围、准确性、精密性及耐用性.将制备的通用检测试剂盒分发给12个实验室,检测各实验室自制的不同表达系统(CHO细胞、毕赤酵母、Sf9细胞或大肠埃希菌)和目的蛋白(RBD或S蛋白)的15批重组SARS-CoV-2蛋白疫苗原液(包括11批以WT株为参考序列设计的原液及4批以Beta、Gamma和Delta变异株设计的原液).结果 确定包被抗体最佳稀释度为1∶500,单克隆抗体20D8作为酶标抗体,最佳稀释度为1∶ 4 000.通用检测试剂盒与严重急性呼吸综合征(SARS)和中东呼吸综合征(Middle East respiratory syndrome,MERS)病毒的重组S蛋白无交叉反应;第1代重组SARS-CoV-2蛋白疫苗抗原国家标准品(简称国家标准品)浓度在0.16～2.50U/mL范围内,与A450/630呈良好的线性关系,线性方程为:y=0.791x-0.1004,R2=0.993 7;0.16～2.50U/mL国家标准品重复6次检测结果回收率均在95％～104％之间,变异系数(coefficient of variation,CV)均＜15％;2名实验员在不同时间重复3次检测结果的CV为4.4％～6.6％;在不同温度及时间条件下检测结果回收率均在80％～120％范围内.15批重组SARS-CoV-2蛋白疫苗原液抗原含量的检测结果与国家标准品均具有良好的平行性.结论 本研究建立的抗原含量通用检测试剂盒具有良好的专属性、准确性、精密性及耐用性,可用于重组SARS-CoV-2蛋白疫苗抗原含量的检测.

目的 建立牛多抗对兔多抗夹心ELISA方法检测Sabin株脊灰病毒灭活疫苗(Sabin strain inactivated poliovirus vaccine,sIPV)D抗原含量,并对建立的方法进行验证.方法 分别采用Ⅰ、Ⅱ、Ⅲ型sIPV疫苗原液作为抗原制备兔多抗,并通过间接ELISA法检测其效价及特异性.以牛多抗为包被抗体、兔多抗为显示抗体建立检测D抗原含量的双抗体夹心ELISA方法,并对方法的准确度、精密度及D抗原专属性进行验证.用建立的方法检测国内5家企业sIPV疫苗样品.结果 制备获得型别特异性好、效价高的Ⅰ、Ⅱ、Ⅲ型兔多抗,并成功建立了双抗体夹心ELISA方法.采用四参数拟合,3型别标准曲线均具有良好的线性关系,R2均＞0.99.Ⅰ、Ⅱ、Ⅲ型各试验加标回收率均为80％～120％,各浓度平均回收率分别为98.11％、97.41％、98.66％;重复性与中间精密度CV均＜10％;能够对D/C抗原进行区分.建立的方法对5家企业生产的sIPV疫苗均能够进行D抗原定量检测.结论 成功建立了检测sIPV疫苗D抗原含量的双抗体夹心ELISA方法,该方法准确度、精密度良好,具有一定的D抗原特异性,能够对不同厂家生产的疫苗进行检测.

Developing variant vaccines or multivalent vaccines is a feasible way to address the epidemic as the SARS-CoV-2 variants of concern (VOCs) posed an increased risk to global public health. The spike protein of the SARS-CoV-2 virus was usually used as the main antigen in many types of vaccines to produce neutralizing antibodies against the virus. However, the spike (S) proteins of different variants were only differentiated by a few amino acids, making it difficult to obtain specific antibodies that can distinguish different VOCs, thereby challenging the accurate distinction and quantification of the variants using immunological methods such as ELISA. Here, we established a method based on LC–MS to quantify the S proteins in inactivated monovalent vaccines or trivalent vaccines (prototype, Delta, and Omicron strains). By analyzing the S protein sequences of the prototype, Delta, and Omicron strains, we identified peptides that were different and specific among the three strains and synthesized them as references. The synthetic peptides were isotopically labeled as internal targets. Quantitative analysis was performed by calculating the ratio between the reference and internal target. The verification results have shown that the method we established had good specificity, accuracy, and precision. This method can not only accurately quantify the inactivated monovalent vaccine but also could be applied to each strain in inactivated trivalent SARS-CoV-2 vaccines. Hence, the LC–MS method established in this study can be applied to the quality control of monovalent and multivalent SARS-CoV-2 variation vaccines. By enabling more accurate quantification, it will help to improve the protection of the vaccine to some extent.

A reference standard is needed for quality control of protein subunit SARS-CoV-2 vaccines to meet urgent domestic needs. The Chinese National Institutes for Food and Drug Control (NIFDC) launched a project to establish the first reference material for the protein subunit SARS-CoV-2 vaccine to be used for calibration of antigen testing. The potency and stability of the national candidate standard (CS) were determined by collaborative calibration, and accelerated and freeze–thaw degradation studies. Moreover, a suitability study of the CS was performed. Eight laboratories in mainland China were asked to detect antigen content of CS using a common validated enzyme-linked immunosorbent assay (ELISA) kit established by NIFDC and in-house kits in the collaborative study. Six laboratories returned valid results, which established that the antigen content of the CS was 876,938 YU/mL, with good agreement across laboratories. In the suitability study, the CS exhibited excellent parallelism and a linear relationship with four samples produced by different expression systems and target proteins. In addition, good stability in the accelerated and freeze–thaw degradation study was observed. In conclusion, the CS was approved by the Biological Product Reference Standards Sub-Committee of the National Drug Reference Standards Committee as the first Chinese national standard for determining antigen content of protein subunit SARS-CoV-2 vaccines, with an assigned antigen content of 877,000 U/mL (Lot. 300050–202101). This standard will contribute to a standardized assessment of protein subunit SARS-CoV-2 vaccine in China and may provide experience for developing reference materials for antigen content detection of SARS-CoV-2 vaccine in other countries.

Because of the relatively limited understanding of coronavirus disease 2019 (COVID-19) pathogenesis, immunological analysis for vaccine development is needed. Mice and macaques were immunized with an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine prepared by two inactivators. Various immunological indexes were tested, and viral challenges were performed on day 7 or 150 after booster immunization in monkeys. This inactivated SARS-CoV-2 vaccine was produced by sequential inactivation with formaldehyde followed by propiolactone. The various antibody responses and specific T cell responses to different viral antigens elicited in immunized animals were maintained for longer than 150 days. This comprehensive immune response could effectively protect vaccinated macaques by inhibiting viral replication in macaques and substantially alleviating immunopathological damage, and no clinical manifestation of immunopathogenicity was observed in immunized individuals during viral challenge. This candidate inactivated vaccine was identified as being effective against SARS-CoV-2 challenge in rhesus macaques.

目的 制备新型冠状病毒S蛋白抗体,初步建立检测新型冠状病毒灭活疫苗抗原含量的方法.方法 使用新型冠状病毒重组S蛋白分别免疫羊和兔,获得抗血清.采用间接ELISA法和微量中和试验检测抗血清效价,免疫印迹试验检测抗体特异性.采用蛋白G纯化树脂分别对羊和兔抗血清进行亲和层析纯化,获得抗体.以纯化后的羊抗体作为包被抗体,兔抗体作为显示抗体,建立新型冠状病毒灭活疫苗抗原含量检测方法.结果 对羊进行4次免疫后,抗血清ELISA效价达220 000,中和抗体效价达1 536.对兔进行3次免疫后,抗血清ELISA效价达220 000,中和抗体效价达4 096.羊和兔抗体均可与新型冠状病毒S蛋白特异性结合.应用纯化后的抗体,成功建立了检测抗原含量的双抗体夹心ELISA方法,该方法线性良好,R2＞0.99,可用于新型冠状病毒灭活疫苗原液抗原含量的检测.结论 成功制备了羊和兔抗新型冠状病毒S蛋白高效价抗体,并初步建立了新型冠状病毒灭活疫苗抗原含量检测的双抗体夹心ELISA方法.

The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutated continuously and newly emerging variants escape from antibody-mediated neutralization raised great concern. S protein is heavily glycosylated and the glycosylation sites are relatively conserved, thus glycans on S protein surface could be a target for the development of anti-SARS-CoV-2 strategies against variants. Here, we collected 12 plant-derived lectins with different carbohydrate specificity and evaluated their anti-SARS-CoV-2 activity against mutant strains and epidemic variants using a pseudovirus-based neutralization assay. The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1. Lentil lectin also showed antiviral activity against SARS-CoV and MERS-CoV. We found lentil lectin could block the binding of ACE2 to S trimer and inhibit SARS-CoV-2 at the early steps of infection. Using structural information and determined N-glycan profile of S trimer, taking together with the carbohydrate specificity of lentil lectin, we provide a basis for the observed broad spectrum anti-SARS-CoV-2 activity. Lentil lectin showed weak haemagglutination activity at 1 mg/mL and no cytotoxicity activity, and no weight loss was found in single injection mouse experiment. This report provides the first evidence that lentil lectin strongly inhibit infection of SARS-COV-2 variants, which should provide valuable insights for developing future anti-SARS-CoV-2 strategies.

Objective To prepare high titer neutralizing antiserum against SARS-CoV-2 Methods SPF rabbits were immunized with RBD protein of SARS-CoV-2, expressed in 293 cells, as an immunogen The prepared antiserum was determined for titer by ELISA and microneutralization test, and distributed to several manufacturers for development of inactivated SARS-CoV-2 vaccine for determination of titer Results After 3 times of immunization, the antiserum titer reached more than 1 600 000, while the neutralizing titer was 8 192 The geometric mean titer (GMT) determined by microneutralization test in five manufacturers was 6 950 Conclusion High titer neutralizing antiserum against SARS-CoV-2 was successfully prepared and distributed to several manufacturers of inactivated SARS-CoV-2 vaccine candidate for virus identification and adventitious virus agent test, which broke through the technical bottleneck restricting the rapid development of SARS-CoV-2 vaccine © 2020 Changchun Institute of Biological Products All rights reserved

Inactivated quadrivalent influenza vaccine (IIV4) containing two influenza A strains (H1N1 and H3N2) and one strain from each B lineage (Victoria and Yamagata) may offer broader protection against seasonal influenza. This study examined the immunogenicity and safety of a candidate IIV4. A randomized, double-blind, controlled phase III clinical trial was conducted in healthy subjects aged >= 3 years. Subjects were randomly assigned into three groups in a 2:1:1 ratio, receiving single dose of IIV4 or inactivated trivalent influenza vaccine (IIV3) which contains either B/Victoria strain (BV) or B/Yamagata strain (BY). Blood samples were collected before and 28 days after vaccination to test hemagglutination inhibition (HI) antibodies of the four influenza strains. Safety information was collected for 28 days after vaccination. A total of 2320 subjects (IIV4: 1160, IIV3-BV: 580, IIV3-BY: 580) were enrolled in this study. After vaccination, the seroconversion rates of IIV4 against H1N1, H3N2, BV and BY strains were 77.15%, 81.93%, 60.14% and 64.57%, respectively. Geometric mean titers (GMTs) against the four influenza strains were 523.91, 274.13, 115.35 and 257.81, respectively. The investigational IIV4 was non-inferiority to IIV3 for the four strains, meanwhile superior to IIV3 for additional B strains (B/BV, B/BY). For safety, there had no significant difference in the incidence of the adverse reactions among the three groups (P = 0.5986). No serious adverse events related to vaccination occurred. The IIV4 had good immunogenicity and safety, which added an influenza B protection with no increased safety concerns. (C) 2020 Elsevier Ltd. All rights reserved.

The ongoing COVID-19 pandemic is causing huge impact on health, life, and global economy, which is characterized by rapid spreading of SARS-CoV-2, high number of confirmed cases and a fatality/case rate worldwide reported by WHO. The most effective intervention measure will be to develop safe and effective vaccines to protect the population from the disease and limit the spread of the virus. An inactivated, whole virus vaccine candidate of SARS-CoV-2 has been developed by Wuhan Institute of Biological Products and Wuhan Institute of Virology. The low toxicity, immunogenicity, and immune persistence were investigated in preclinical studies using seven different species of animals. The results showed that the vaccine candidate was well tolerated and stimulated high levels of specific IgG and neutralizing antibodies. Low or no toxicity in three species of animals was also demonstrated in preclinical study of the vaccine candidate. Biochemical analysis of structural proteins and purity analysis were performed. The inactivated, whole virion vaccine was characterized with safe double-inactivation, no use of DNases and high purity. Dosages, boosting times, adjuvants, and immunization schedules were shown to be important for stimulating a strong humoral immune response in animals tested. Preliminary observation in ongoing phase I and II clinical trials of the vaccine candidate in Wuzhi County, Henan Province, showed that the vaccine is well tolerant. The results were characterized by very low proportion and low degree of side effects, high levels of neutralizing antibodies, and seroconversion. These results consistent with the results obtained from preclinical data on the safety.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. Because of the novelty of the virus, there are currently no SARS-CoV-2-specific treatments or vaccines available. Therefore, rapid development of effective vaccines against SARS-CoV-2 are urgently needed. Here, we developed a pilot-scale production of PiCoVacc, a purified inactivated SARS-CoV-2 virus vaccine candidate, which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats, and nonhuman primates. These antibodies neutralized 10 representative SARS-CoV-2 strains, suggesting a possible broader neutralizing ability against other strains. Three immunizations using two different doses, 3 or 6 micrograms per dose, provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. These data support the clinical development and testing of PiCoVacc for use in humans.