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The global spread of COVID-19 has prompted the development of vaccines. A recombinant adenovirus type-5 vectored COVID-19 vaccine (Ad5-nCoV) developed by Chinese scientists has been authorized for use as a prime and booster dose in China and several other countries. We searched published articles as of 4 May 2023, on PubMed using keywords related to Adenovirus vector, vaccine, and SARS-CoV-2. We reported the progress and outcomes of Ad5-nCov, including vaccine efficacy, safety, immunogenicity based on pre-clinical trials, clinical trials, and real-world studies for primary and booster doses. Ad5-nCoV is a significant advancement in Chinese vaccine development technology. Evidence from clinical trials and real-world studies has demonstrated well-tolerated, highly immunogenic, and efficacy of Ad5-nCoV in preventing severe/critical COVID-19. Aerosolized Ad5-nCoV, given via a novel route, could elicit mucosal immunity and improve the vaccine efficacy, enhance the production capacity and availability, and reduce the potential negative impact of preexisting antibodies. However, additional research is necessary to evaluate the long-term safety and immunogenicity of Ad5-nCoV, its efficacy against emerging variants, its effectiveness in a real-world context of hybrid immunity, and its cost-effectiveness, particularly with respect to aerosolized Ad5-nCoV. [ABSTRACT FROM AUTHOR]

The certification of immunogenicity consistency at different production scales is indispensable for the quality control of vaccines. A randomized, double-blind immunobridging trial in healthy adults aged 18–59 was divided into Scale A (50 L and 800 L) and Scale B (50 L and 500 L) based on vaccine manufacturing scales. Eligible participants in Scale A were randomly assigned to receive the single-dose recombinant adenovirus type-5 vectored COVID-19 vaccine (Ad5-nCoV) of different scales at a 1:1 ratio, as was Scale B. The primary endpoint was the geometric mean titer (GMT) of anti-live SARS-CoV-2-specific neutralizing antibodies (NAb) 28 days post-vaccination. 1,012 participants were enrolled, with 253 (25%) per group. The post-vaccination GMTs of NAb were 10.72 (95% CI: 9.43, 12.19) and 13.23 (11.64, 15.03) in Scale A 50 L and 800 L, respectively; 11.64 (10.12, 13.39) and 12.09 (10.48, 13.95) in Scale B 50 L and 500 L, respectively. GMT ratios in Scale A and B have a 95% CI of 0.67–1.5. Most adverse reactions were mild or moderate. 17 of 18 participants reported non-vaccination-related serious adverse reactions. The Ad5-nCoV in the scale-up production of 500 L and 800 L showed consistent immunogenicity with the original 50 L production scale, respectively. [ABSTRACT FROM AUTHOR]

The demonstration of batch-to-batch consistency is indispensable for quality control of vaccines. We conducted a randomized, double-blind, parallel-controlled trial to evaluate the immunogenicity consistency of a single shot of Ad5-nCoV in healthy adults who had not previously received any COVID-19 vaccine. All eligible participants were randomly assigned equally to receive one of the three consecutive batches of Ad5-nCoV (5 × 1010 viral particles/vial, 0.5 mL). The primary endpoint was geometric mean titers (GMTs) of serum SARS-CoV-2 receptor-binding domain (RBD)-specific IgG on day 28 post-vaccination. One thousand fifty participants were enrolled, with 350 (33%) participants per group. On day 28 post-vaccination, GMTs in three groups were 78.3 binding antibody units (BAU)/mL (95% CI 70.3–87.3), 82.9 BAU/mL (73.9–92.9), and 78.8 BAU/mL (70.2–88.4), respectively. The two-sided 95% CIs for the GMT ratios between each pair of batches were all between 0.67 and 1.5. The highest incidence of solicited adverse reactions within 7 days post-vaccination was reported by batch 3 recipients (23.1% versus 15.1% in batch 1 recipients and 14.6% in bath 2 recipients; p = 0.0039). None of the serious adverse events were related to vaccination. Immunogenicity consistency between consecutive batches of Ad5-nCoV was well established in adults. This trial was registered with ClinicalTrials.gov (NCT05313646). [ABSTRACT FROM AUTHOR]

Quadrivalent Influenza Vaccine (Sinovac Biotech) is a quadrivalent split-virion-inactivated influenza vaccine approved in China in June 2020 for individuals ≥3 years of age. It contains 15 µg hemagglutinin per strain including A/H1N1, A/H3N2, B/Victoria, and B/Yamagata, which could potentially improve protection against influenza B viruses. In this review, we summarize the development of quadrivalent influenza vaccines in China and foreign countries, and assess the immunogenicity and safety from the phase I and III clinical trials of Quadrivalent Influenza Vaccine in individuals ≥3 years of age. We also discuss the potential application of Quadrivalent Influenza Vaccine in young children 6–35 months of age according to the results of the phase III trial. The immunogenicity and safety profiles of Quadrivalent Influenza Vaccine containing two A and two B strains were comparable to the trivalent vaccines for the shared strains. The addition of a second B strain to the trivalent vaccine could induce superior immune responses for the alternate B strain. Since the two B strains co-circulated worldwide, the introduction of quadrivalent influenza vaccines has been expected to be a cost-effective strategy. [ABSTRACT FROM AUTHOR]

Background: The Sinovac enterovirus 71 (EV71) vaccine has shown good safety, immunogenicity, and efficacy in infants aged 6–35 months, whom are considered as the priority of the target population. However, 3–5 years old children accounted for approximately 30% of HFMD cases and are also worth our attention. Methods: A randomized, double-blind, placebo-controlled, batch-to-batch consistency clinical trial enrolling 1400 participants aged 6–59 months was performed. We pooled the participants receiving three batches of EV71 vaccine together and then stratified them into the 6–35 months and 3–5 years. The non-inferiority analysis of the geometric mean titer (GMT) of EV71 neutralizing antibody post-vaccination was the primary endpoint. Results: In the vaccine group, the GMT of 242 children aged 3–5 years was 132.72 (95% CI, 110.3–159.6), which was non-inferior to that generated in 717 infants aged 6–35 months. Following the vaccination, the incidence of adverse reactions was less frequent in children aged 3–5 years (47.0%) than that found in infants aged 6–35 months (60.1%) (p = 0.0026). Conclusions: Our study indicated that the EV71 vaccine was also safe in children aged 3–5 years, with non-inferior immunogenicity to that in infants aged 6–35 months. [ABSTRACT FROM PUBLISHER]

Background:Viruses from two antigenically distinct influenza B strains have co-circulated since the mid-1980s, yet inactivated trivalent influenza vaccines (TIVs) with either the Victoria or Yamagata lineage could only provide limited protection from influenza B strain. Quadrivalent influenza vaccine (QIV) including both influenza B lineages can improve protection against circulating influenza B viruses. Methods:Participants >/ = 3 years of age were recruited, stratified by age, and then randomly allocated at a ratio of 2:1:1 to receive one-injection of the experimental QIV, TIV-Victoria (Vic) or TIV-Yamagata (Yam). The primary objective of this study was to demonstrate that the hemagglutination-inhibition (HI) antibodies induced by the QIV candidate are not inferior to the licensed TIVs. Results:First, 3661 participants received the inoculation. The QIV was found to be non-inferior to TIVs in terms of the geometric mean titers (GMTs) and seroconversion rates (SCRs) of the HI antibodies against shared strains 28 days after completion of inoculation, and was superior to the TIVs against the alternate B strain, which is absent from the TIVs. The occurrences of adverse events (AEs) post-vaccination were similar across the treatment groups. Conclusion:The experimental QIV showed good immunogenicity and an acceptable safety profile. [ABSTRACT FROM PUBLISHER]

Background: Inactivated Enterovirus 71 (EV71) vaccines showed significant efficacy against the diseases associated with EV71 and a neutralizing antibody (NTAb) titer of 1:16–1:32 was suggested as the correlates of the vaccine protection. This paper aims to further estimate the immunological surrogate endpoints for the protection of inactivated EV71 vaccines and the effect factors. Methods: Pre-vaccination NTAb against EV71 at baseline (day 0), post-vaccination NTAb against EV71 at day 56, and the occurrence of laboratory-confirmed EV71-associated diseases during a 24-months follow-up period were collected from a phase 3 efficacy trial of an inactivated EV71 vaccine. We used the mixed-scaled logit model and the absolute sigmoid function by some extensions in continuous models to estimate the immunological surrogate endpoint for the EV71 vaccine protection, respectively. Results: For children with a negative baseline of EV71 NTAb titers, an antibody level of 26.6 U/ml (1:30) was estimated to provide at least a 50% protection for 12 months, and an antibody level of 36.2 U/ml (1:42) may be needed to achieve a 50% protective level of the population for 24 months. Conclusion: Both the pre-vaccination NTAb level and the vaccine protective period could affect the estimation of the immunological surrogate for EV71 vaccine. A post-vaccination NTAb titer of 1:42 or more may be needed for long-term protection. Clinical trial registration: NCT01508247. [ABSTRACT FROM PUBLISHER]

Background: The objective of this study was to evaluate the immunogenicity and safety of the novel combined Haemophilus influenzae type b–Neisseria meningitidis serogroup A and C–tetanus toxoid conjugate vaccine (Hib-MenAC). Methods: We conducted a non-inferiority, randomized, observer-blind, positive control clinical trial in 900 healthy infants aged between 3–5 months in Funing County, Jiangsu Province, China. Participants were randomly allocated, in a ratio of 2:1 (block = 6), to receive experimental combined Hib-MenAC vaccines co-administrated with placebo or the co-administration of licensed Hib vaccine and MenAC vaccine, according to a three-dose immunization schedule. The seroconversion of antibody titer against meningococcal serogroups A, C and Hib was the primary endpoint. Results: The experimental vaccines was non-inferior to the licensed two control vaccines. Participants receiving experimental Hib-MenAC vaccines showed a seroconversion rate of 99.0%, 96.1% and 97.7% for rSBA-MenA, rSBA-MenC and anti-PRP antibodies, respectively. The Hib-MenAC vaccine did not result in an increase in adverse reaction, and no serious adverse event was judged to be related to the vaccination. Conclusions: The novel combined Hib-MenAC conjugate vaccine was safe and highly immunogenic in infants aged between 3 to 5 months. [ABSTRACT FROM PUBLISHER]

Introduction: Enterovirus A71 (EV71) is the predominant causative agent of hand, foot, and mouth disease (HFMD), which is often associated with severe cases and even deaths. EV71-associated epidemics have emerged as a serious threat to public health, particularly in the Asia-Pacific region. Areas covered: We searched PubMed using the terms ‘enterovirus 71’, ‘hand, foot, and mouth disease’, and ‘vaccine’, with no date or language restrictions for all publications before April 27, 2016. Among various vaccine candidates, the alum-adjuvant inactivated EV71 vaccines are most promising. Three alum-adjuvant inactivated EV71 vaccines developed by mainland China showed high efficacy, good immunogenicity persistence and acceptable safety profiles in clinical trials. Recently, two of these EV71 vaccines have been approved for marketing in China and the other one is undergoing the review process of licensure. In this manuscript, we summarized previous study results as well as discussed the regulatory affairs and post-market surveillances issues. Expert commentary: The marketing of EV71 vaccines is a milestone in the controlling of HFMD. International clinical trials are needed to further assess the efficacy and cross-immunogenicity. Establishing a sensitive pathogen monitoring system would be essential to monitor the variation of genotypes and control HFMD epidemics. [ABSTRACT FROM PUBLISHER]

Objectives: To evaluate the efficacy and immunogenicity of the Sinovac Enterovirus 71 (EV71) vaccine for up to two years.Methods: We did a follow-up study of our initial randomized trial in 10,077 participants, who were randomized to receive EV71 vaccine or placebo in a 1:1 ratio and followed for 14 months. The extended follow-up study lasted for another 12 months and EV71-associated hand, foot, and mouth disease (HFMD) was the primary endpoint.Results: The EV71 vaccine showed an efficacy of 95.1% (95%CI 63.6, 99.3) against EV71-associated HFMD during the extended follow-up and an overall efficacy of 94.7% (95%CI 87.8, 97.6) for two years. The EV71 vaccine elicited a sustained high level of neutralizing antibodies in participants, and no serious adverse event was judged to be related to the vaccination.Conclusion: The Sinovac EV71 vaccine could provide a sustained high protection against EV71-associated HFMDs for up to 2 years. [ABSTRACT FROM PUBLISHER]

The widespread epidemics of enterovirus 71 (EV71) seriously affected the Western Pacific Region. Young children, especially those younger than 3 years are the most susceptible population to the EV71-associated diseases. Several Asian countries have begun to focus on the research and development of EV71 vaccines. Five inactivated whole-virus EV71 candidate vaccines (three were manufactured in mainland China based on a C4 genotype strain, one in Taiwan based on a B4 genotype strain and one in Singapore based on a B2 genotype strain) have been assessed in clinical trials. Three candidate vaccines developed in mainland China have already completed Phase III clinical trials recently. The tested EV71 vaccine could provide good efficacy, satisfactory safety, and high immunogenicity. Thus, inactivated EV71 vaccines are expected to become the first available vaccines against EV71 in the near future. [ABSTRACT FROM AUTHOR]