The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the waning of vaccine-elicited neutralizing antibodies suggests that additional coronavirus disease 2019 ...(COVID-19) vaccine doses may be needed for individuals who initially received CoronaVac. We evaluated the safety and immunogenicity of the recombinant adenovirus type 5 (AD5)-vectored COVID-19 vaccine Convidecia as a heterologous booster versus those of CoronaVac as homologous booster in adults previously vaccinated with CoronaVac in an ongoing, randomized, observer-blinded, parallel-controlled phase 4 trial ( NCT04892459 ). Adults who had received two doses of CoronaVac in the past 3-6 months were vaccinated with Convidecia (n = 96) or CoronaVac (n = 102). Adults who had received one dose of CoronaVac in the past 1-3 months were also vaccinated with Convidecia (n = 51) or CoronaVac (n = 50). The co-primary endpoints were the occurrence of adverse reactions within 28 d after vaccination and geometric mean titers (GMTs) of neutralizing antibodies against live wild-type SARS-CoV-2 virus at 14 d after booster vaccination. Adverse reactions after vaccination were significantly more frequent in Convidecia recipients but were generally mild to moderate in all treatment groups. Heterologous boosting with Convidecia elicited significantly increased GMTs of neutralizing antibody against SARS-CoV-2 than homologous boosting with CoronaVac in participants who had previously received one or two doses of CoronaVac. These data suggest that heterologous boosting with Convidecia following initial vaccination with CoronaVac is safe and more immunogenic than homologous boosting.
An effective vaccine is needed to end the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Here, we assess the preliminary safety, tolerability and immunogenicity data from an ...ongoing single-center (in Jiangsu province, China), parallel-group, double-blind phase 1 trial of the vaccine candidate BNT162b1 in 144 healthy SARS-CoV-2-naive Chinese participants. These participants are randomized 1:1:1 to receive prime and boost vaccinations of 10 µg or 30 µg BNT162b1 or placebo, given 21 d apart, with equal allocation of younger (aged 18-55 years) and older adults (aged 65-85 years) to each treatment group (ChiCTR2000034825). BNT162b1 encodes the SARS-CoV-2 spike glycoprotein receptor-binding domain (RBD) and is one of several messenger RNA-based vaccine candidates under clinical investigation. Local reactions and systemic events were generally dose dependent, transient and mild to moderate. Fever was the only grade 3 adverse event. BNT162b1 induced robust interferon-γ T cell responses to a peptide pool including the RBD in both younger and older Chinese adults, and geometric mean neutralizing titers reached 2.1-fold (for younger participants) and 1.3-fold (for the older participants) that of a panel of COVID-19 convalescent human sera obtained at least 14 d after positive SARS-CoV-2 polymerase chain reaction test. In summary, BNT162b1 has an acceptable safety profile and produces high levels of humoral and T cell responses in an Asian population.
In response to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, over 200 vaccine candidates against coronavirus disease 2019 (COVID-2019) are under development and currently ...moving forward at an unparalleled speed. The availability of surrogate endpoints would help to avoid large-scale filed efficacy trials and facilitate the approval of vaccine candidates, which is crucial to control COVID-19 pandemic. Several phase 3 efficacy trials of COVID-19 vaccine candidates are under way, which provide opportunities for the determination of COVID-19 correlates of protection. In this paper, we review current knowledge for existence of COVID-19 correlates of protection, methods for assessment of immune correlates of protection and issues related to COVID-19 correlates of protection.
Enterovirus 71 (EV71) is an important cause of hand, foot, and mouth disease, especially in China. In this phase 3 trial involving 10,077 infants and children in China, an EV71 vaccine provided ...protection against EV71-associated disease.
Enterovirus 71 (EV71), an enterovirus that is not associated with poliomyelitis, was one of the major causative agents of outbreaks of hand, foot, and mouth disease or herpangina in Europe,
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between 1972 and 1988, and it has been implicated in a series of outbreaks across the Asia–Pacific region since the 1990s.
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The largest Asia–Pacific epidemic occurred in China in 2008, when approximately 490,000 infections and 126 deaths in infants and young children were reported.
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The vast majority of severe cases and fatal cases occurred in children younger than 3 years of age. EV71 . . .
CoronaVac, also known as the Sinovac inactivated SARS-CoV-2 vaccine, has been widely implemented in combating the COVID-19 pandemic. We summarized the results of clinical trials and real-world ...studies of CoronaVac in this review. The overall efficacy for the prevention of symptomatic COVID-19 (before the emergence of variants of concern) using two doses of 3 μg CoronaVac was 67.7% (95% CI, 35.9% to 83.7%). Effectiveness in preventing hospitalizations, ICU admissions, and deaths was more prominent than that in preventing COVID-19. A third dose inherited the effectiveness against non-variants of concern and increased effectiveness against severe COVID-19 outcomes caused by omicron variants compared to two doses. Most adverse reactions were mild. Few vaccine-related serious adverse reactions have been reported. Moreover, three-dose regimen significantly increased the seroconversion levels of neutralizing antibodies against omicron as compared to two-dose regimen. This review of CoronaVac may provide a scientific basis for optimizing global immunization strategies.
Receptor usage that determines cell tropism and drives viral classification closely correlates with the virus structure. Enterovirus B (EV-B) consists of several subgroups according to receptor ...usage, among which echovirus 30 (E30), a leading causative agent for human aseptic meningitis, utilizes FcRn as an uncoating receptor. However, receptors for many EVs remain unknown. Here we analyzed the atomic structures of E30 mature virion, empty- and A-particles, which reveals serotype-specific epitopes and striking conformational differences between the subgroups within EV-Bs. Of these, the VP1 BC loop markedly distinguishes E30 from other EV-Bs, indicative of a role as a structural marker for EV-B. By obtaining cryo-electron microscopy structures of E30 in complex with its receptor FcRn and CD55 and comparing its homologs, we deciphered the underlying molecular basis for receptor recognition. Together with experimentally derived viral receptor identifications, we developed a structure-based in silico algorithm to inform a rational prediction for EV receptor usage.
The current outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in China firstly. A rapid, highly sensitive, specific, ...and simple operational method was needed for the detection of SARS-CoV-2. Here, we established a real-time reverse-transcription recombinase-aided amplification assay (RT-RAA) to detect SARS-CoV-2 rapidly. The primers and probe were designed based on the nucleocapsid protein gene (N gene) sequence of SARS-CoV-2. The detection limit was 10 copies per reaction in this assay, which could be conducted within 15 min at a constant temperature (39 °C), without any cross-reactions with other respiratory tract pathogens, such as other coronaviruses. Furthermore, compared with commercial real-time RT-PCR assay, it showed a kappa value of 0.959 (p < 0.001) from 150 clinical specimens. These results indicated that this real-time RT-RAA assay may be a valuable tool for detecting SARS-CoV-2.
Heterologous boost vaccination has been proposed as an option to elicit stronger and broader, or longer-lasting immunity. We assessed the safety and immunogenicity of heterologous immunization with a ...recombinant adenovirus type-5-vectored Coronavirus Disease 2019 (COVID-19) vaccine (Convidecia, hereafter referred to as CV) and a protein-subunit-based COVID-19 vaccine (ZF2001, hereafter referred to as ZF).
We conducted a randomized, observer-blinded, placebo-controlled trial, in which healthy adults aged 18 years or older, who have received 1 dose of Convidecia, with no history of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, were recruited in Jiangsu, China. Sixty participants were randomly assigned (2:1) to receive either 1 dose of ZF2001 or placebo control (trivalent inactivated influenza vaccine (TIV)) administered at 28 days after priming, and received the third injection with ZF2001 at 5 months, referred to as CV/ZF/ZF (D0-D28-M5) and CV/ZF (D0-M5) regimen, respectively. Sixty participants were randomly assigned (2:1) to receive either 1 dose of ZF2001 or TIV administered at 56 days after priming, and received the third injection with ZF2001 at 6 months, referred to as CV/ZF/ZF (D0-D56-M6) and CV/ZF (D0-M6) regimen, respectively. Participants and investigators were masked to the vaccine received but not to the boosting interval. Primary endpoints were the geometric mean titer (GMT) of neutralizing antibodies against wild-type SARS-CoV-2 and 7-day solicited adverse reactions. The primary analysis was done in the intention-to-treat population. Between April 7, 2021 and May 6, 2021, 120 eligible participants were randomly assigned to receive ZF2001/ZF2001 (n = 40) or TIV/ZF2001 (n = 20) 28 days and 5 months post priming, and receive ZF2001/ZF2001 (n = 40) or TIV/ZF2001 (n = 20) 56 days and 6 months post priming. Of them, 7 participants did not receive the third injection with ZF2001. A total of 26 participants (21.7%) reported solicited adverse reactions within 7 days post boost vaccinations, and all the reported adverse reactions were mild, with 13 (32.5%) in CV/ZF/ZF (D0-D28-M5) regimen, 7 (35.0%) in CV/ZF (D0- M5) regimen, 4 (10.0%) in CV/ZF/ZF (D0-D56-M6) regimen, and 2 (10.0%) in CV/ZF (D0-M6) regimen, respectively. At 14 days post first boost, GMTs of neutralizing antibodies in recipients receiving ZF2001 at 28 days and 56 days post priming were 18.7 (95% CI 13.7 to 25.5) and 25.9 (17.0 to 39.3), respectively, with geometric mean ratios of 2.0 (1.2 to 3.5) and 3.4 (1.8 to 6.4) compared to TIV. GMTs at 14 days after second boost of neutralizing antibodies increased to 107.2 (73.7 to 155.8) in CV/ZF/ZF (D0-D28-M5) regimen and 141.2 (83.4 to 238.8) in CV/ZF/ZF (D0-D56-M6) regimen. Two-dose schedules of CV/ZF (D0-M5) and CV/ZF (D0-M6) induced antibody levels comparable with that elicited by 3-dose schedules, with GMTs of 90.5 (45.6, 179.8) and 94.1 (44.0, 200.9), respectively. Study limitations include the absence of vaccine effectiveness in a real-world setting and current lack of immune persistence data.
Heterologous boosting with ZF2001 following primary vaccination with Convidecia is more immunogenic than a single dose of Convidecia and is not associated with safety concerns. These results support flexibility in cooperating viral vectored and recombinant protein vaccines.
Study on Heterologous Prime-boost of Recombinant COVID-19 Vaccine (Ad5 Vector) and RBD-based Protein Subunit Vaccine; ClinicalTrial.gov NCT04833101.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Rabies is a highly fatal zoonotic disease caused by the rabies virus invading the central nervous system. When suspected of exposure to the rabies virus, post-exposure prophylaxis should be ...administered as soon as possible. Monoclonal antibodies (mAbs) neutralizing the rabies virus could be better in human rabies post-exposure prophylaxis than equine or human rabies immune globulin in terms of supply, cost, and efficacy. This article reviews anti-rabies mAbs produced by multiple techniques, and the results of clinical trials for anti-rabies mAbs cocktails recognizing non-overlapping epitopes are also discussed.
Among seven coronaviruses that infect humans, three (severe acute respiratory syndrome coronavirus SARS-CoV, Middle East respiratory syndrome coronavirus MERS-CoV, and the newly identified severe ...acute respiratory syndrome coronavirus 2 SARS-CoV-2) are associated with a severe, life-threatening respiratory infection and multiorgan failure. We previously proposed that the cationically modified chitosan N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC) is a potent inhibitor of human coronavirus NL63 (HCoV-NL63). Next, we demonstrated the broad-spectrum antiviral activity of the compound, as it inhibited all low-pathogenicity human coronaviruses (HCoV-NL63, HCoV-229E, HCoV-OC43, and HCoV-HKU1). Here, using
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models of human airway epithelia, we show that HTCC effectively blocks MERS-CoV and SARS-CoV-2 infection. We also confirmed the mechanism of action for these two viruses, showing that the polymer blocks the virus entry into the host cell by interaction with the S protein.
The beginning of 2020 brought us information about the novel coronavirus emerging in China. Rapid research resulted in the characterization of the pathogen, which appeared to be a member of the SARS-like cluster, commonly seen in bats. Despite the global and local efforts, the virus escaped the health care measures and rapidly spread in China and later globally, officially causing a pandemic and global crisis in March 2020. At present, different scenarios are being written to contain the virus, but the development of novel anticoronavirals for all highly pathogenic coronaviruses remains the major challenge. Here, we describe the antiviral activity of an HTCC compound, previously developed by us, which may be used as a potential inhibitor of currently circulating highly pathogenic coronaviruses-SARS-CoV-2 and MERS-CoV.
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