Boosting with an aerosolized Ad5-nCoV elicited robust immune responses in inactivated COVID-19 vaccines recipients

IntroductionThe SARS-CoV-2 Omicron variant has become the dominant SARS-CoV-2 variant and exhibits immune escape to current COVID-19 vaccines, the further boosting strategies are required.MethodsWe have conducted a non-randomized, open-label and parallel-controlled phase 4 trial to evaluate the magnitude and longevity of immune responses to booster vaccination with intramuscular adenovirus vectored vaccine (Ad5-nCoV), aerosolized Ad5-nCoV, a recombinant protein subunit vaccine (ZF2001) or homologous inactivated vaccine (CoronaVac) in those who received two doses of inactivated COVID-19 vaccines. ResultsThe aerosolized Ad5-nCoV induced the most robust and long-lasting neutralizing activity against Omicron variant and IFNg T-cell response among all the boosters, with a distinct mucosal immune response. SARS-CoV-2-specific mucosal IgA response was substantially generated in subjects boosted with the aerosolized Ad5-nCoV at day 14 post-vaccination. At month 6, participants boosted with the aerosolized Ad5-nCoV had remarkably higher median titer and seroconversion of the Omicron BA.4/5-specific neutralizing antibody than those who received other boosters. DiscussionOur findings suggest that aerosolized Ad5-nCoV may provide an efficient alternative in response to the spread of the Omicron BA.4/5 variant.Clinical trial registrationhttps://www.chictr.org.cn/showproj.html?proj=152729, identifier ChiCTR2200057278

Interactive Online Advertising: The Effectiveness of Marketing Strategy towards Customers Purchase Decision

A growing of IT industry made many companies used Internet as their mediators on advertising platform to control over the promotion materials and it possess greater reliability and flexibility. Internet also becoming an important stop point for customers in finding their needs and wants. This study has been designed to measures how significant is the online advertising effectiveness in terms of attitude towards ads, ability to recall ads and frequency of clicking ads in explaining purchase decision in Malacca, Malaysia. A series of survey was conducted from 200 respondents and were analyzed quantatively. The results showed among the attitude towards ads, ability to recall and frequency of clicking ads had significantly gave impact to the purchasing decision by the customers. For the recommendations discussed to the advertisers to have good understanding on how to advertise effectively (using marketing strategy program) and do some innovation of the products in terms of the products association

Safety and Immunogenicity of Homologous Recombinant Adenovirus Type 5-Vectored COVID-19 Vaccine Booster Dose in Healthy Adults Aged 18–60 Years: a Single-Center, Open-Label Trial

Abstract Introduction The waning antibody levels several months after prime vaccination and the persistent epidemics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) around the world have generated great interest in the evaluation of a booster dose. We aimed to assess the safety and immunogenicity of a homologous booster dose of the recombinant adenovirus type 5-vectored coronavirus disease 2019 (COVID-19) vaccine (Ad5-nCoV). Methods In this trial, we recruited healthy adults aged 18–60 years who had received one dose of Ad5-nCoV vaccine (low, middle, or high dose) in the previous phase 1 trial approximately 6 months earlier, and then all participants received a booster dose of 5 × 1010 viral particles (low dose) intramuscularly. The primary outcome was the incidence of adverse reactions within 14 days after booster vaccination. The specific binding antibodies were measured by enzyme-linked immunosorbent assay and the neutralizing antibody responses were assessed with live SARS-CoV-2 and pseudovirus neutralization assay. The cellular immune responses were analyzed by enzyme-linked immunospot assay and intracellular cytokine staining. Results From September 26 to 28, 2020, 108 volunteers were recruited and 89 eligible participants (52% male) were enrolled and received a booster dose of Ad5-nCoV vaccine: 28 (31%) had received a low prime dose, 30 (34%) a middle prime dose, and 31 (35%) a high prime dose in the previous phase 1 trial. All participants were included in the safety analysis and immunogenicity was assessed in 88 (99%) participants. Twenty-three (82%) participants in the low prime dose group, 23 (77%) participants in the middle prime dose group, and 26 (84%) participants in the high prime dose group reported at least one adverse reaction within the first 14 days post booster. Pain at the injection site and fatigue were the most common adverse reactions. Most adverse reactions were mild or moderate in all groups and no vaccine-related severe adverse event was noted within 12 months after booster vaccination. Neutralizing antibodies increased moderately at day 14 and peaked at 28 days post booster. T cell responses were also boosted at 14 days after vaccination. Conclusions A homologous booster of Ad5-nCoV vaccine is well tolerated and immunogenic in healthy adults aged 18–60 years who had received a priming dose of Ad5-nCoV 6 months previously. The neutralizing antibodies against SARS-CoV-2 peaked at day 28 and specific T cell responses were noted at day 14 after booster. Ad5-nCoV vaccine can be considered as a homologous booster 6 months after a priming dose. Trial registration ClinicalTrials.gov, NCT04568811

Seroepidemiological investigation of HAdV-4 infection among healthy adults in China and in Sierra Leone, West Africa

Abstract An apparent increase in the frequency of human adenovirus type 4 (HAdV-4) infections among general populations has been observed over the past 10 years. However, available epidemiological data that may reflect previous viral circulation and assist in predicting potential outbreaks are sparse, particularly in mainland China and Africa. In this study, a convenient neutralization assay for use in the surveillance of historical HAdV-4 infections was established based on a recombinant luciferase-expressing virus. Subsequently, the neutralizing antibodies (nAbs) of 1013 healthy adult serum samples from China and Sierra Leone were evaluated. Our results showed that over 50% of the participants from China and nearly 70% of donors from Sierra Leone had detectable nAbs against HAdV-4 despite the few infection cases officially reported in these regions. Furthermore, the prevalence of nAbs to HAdV-4 is lower than that to HAdV-5, and both varied by geographic location. In addition, the seropositive rates of both HAdV-4 and HAdV-5 nAbs increased with age. However, the nAbs stimulated by HAdV-4 remained stable at low (≤200) levels among the different age groups, whereas moderate (201–1000) or high (>1000) nAb levels were produced by HAdV-5 and tended to decrease with age. These results elucidate the human humoral immune response against HAdV-4 and revealed that this virus may be an underestimated causative agent of respiratory disease among adults in China and West Africa, demonstrating the importance of HAdV-4 surveillance and providing useful insights for the future development of HAdV-4-based vaccines

A single dose of an adenovirus-vectored vaccine provides protection against SARS-CoV-2 challenge

A vaccine preventing infection and transmission of SARS-CoV-2 is needed. Here, Wu et al. generate an adenovirus-vector vaccine expressing SARS-CoV-2 spike protein and show that a single dose of mucosal vaccination protects mice and ferrets from infection and inhibits virus replication in the upper respiratory tract

Image_5_Boosting with an aerosolized Ad5-nCoV elicited robust immune responses in inactivated COVID-19 vaccines recipients.jpeg

IntroductionThe SARS-CoV-2 Omicron variant has become the dominant SARS-CoV-2 variant and exhibits immune escape to current COVID-19 vaccines, the further boosting strategies are required.MethodsWe have conducted a non-randomized, open-label and parallel-controlled phase 4 trial to evaluate the magnitude and longevity of immune responses to booster vaccination with intramuscular adenovirus vectored vaccine (Ad5-nCoV), aerosolized Ad5-nCoV, a recombinant protein subunit vaccine (ZF2001) or homologous inactivated vaccine (CoronaVac) in those who received two doses of inactivated COVID-19 vaccines. ResultsThe aerosolized Ad5-nCoV induced the most robust and long-lasting neutralizing activity against Omicron variant and IFNg T-cell response among all the boosters, with a distinct mucosal immune response. SARS-CoV-2-specific mucosal IgA response was substantially generated in subjects boosted with the aerosolized Ad5-nCoV at day 14 post-vaccination. At month 6, participants boosted with the aerosolized Ad5-nCoV had remarkably higher median titer and seroconversion of the Omicron BA.4/5-specific neutralizing antibody than those who received other boosters. DiscussionOur findings suggest that aerosolized Ad5-nCoV may provide an efficient alternative in response to the spread of the Omicron BA.4/5 variant.Clinical trial registrationhttps://www.chictr.org.cn/showproj.html?proj=152729, identifier ChiCTR2200057278.</p