Preliminary findings from the Dynamics of the Immune Responses to Repeat Influenza Vaccination Exposures (DRIVE I) Study: a Randomized Controlled Trial.

BACKGROUND: Studies have reported that repeated annual vaccination may influence influenza vaccination effectiveness in the current season. METHODS: We established a 5-year randomized placebo-controlled trial of repeated influenza vaccination (Flublok, Sanofi Pasteur) in adults 18-45 years of age. In the first two years, participants received vaccination (V) or saline placebo (P) as follows: P-P, P-V, or V-V. Serum samples were collected each year just before vaccination and after 30 and 182 days. A subset of sera collected at 5 timepoints from 95 participants were tested for antibodies against vaccine strains. RESULTS: From 23 October 2020 through 11 March 2021 we enrolled and randomized 447 adults. Among vaccinated individuals, antibody titers increased between days 0 and 30 against each of the vaccine strains, with smaller increases for repeat vaccinees who on average had higher pre-vaccination titers in year 2. There were statistically significant differences in the proportion of participants achieving >=four-fold rises in antibody titer for the repeat vaccinees for influenza A(H1N1), B/Victoria and B/Yamagata, but not for A(H3N2). Among participants who received vaccination in year 2, there were no statistically significant differences between the P-V and V-V groups in geometric mean titers at day 30 or the proportions of participants with antibody titers ≥40 at day 30 for any of the vaccine strains. CONCLUSIONS: In the first two years, during which influenza did not circulate, repeat vaccinees and first-time vaccinees had similar post-vaccination geometric mean titers to all four vaccine strains, indicative of similar levels of clinical protection.

Avian Influenza A(H5N1) Neuraminidase Inhibition Antibodies in Healthy Adults after Exposure to Influenza A(H1N1)pdm09.

We detected high titers of cross-reactive neuraminidase inhibition antibodies to influenza A(H5N1) virus clade 2.3.4.4b in 96.8% (61/63) of serum samples from healthy adults in Hong Kong in 2020. In contrast, antibodies at low titers were detected in 42% (21/50) of serum samples collected in 2009. Influenza A(H1N1)pdm09 and A(H5N1) titers were correlated.

Genetic diversity of astroviruses detected in wild aquatic birds in Hong Kong.

Wild waterfowl serve as a reservoir of some astroviruses. Fecal samples from wild waterfowl collected at Hong Kong's Marshes were tested using pan-astrovirus reverse transcription-PCR. Positive samples underwent subsequent host identification using DNA barcoding. Based on deduced partial sequences, noteworthy samples from three astrovirus groups (mammalian, avian and unclassified astroviruses) were further analyzed by next-generation sequencing. One sample of Avastrovirus 4 clade, MP22-196, had a nearly complete genome identified. The results of ORF2 phylogenetic analysis and genetic distance analysis indicate that Avastrovirus 4 is classified as a distinct subclade within Avastrovirus. MP22-196 has typical astrovirus genome characteristics. The unique characteristics and potential differences of this genome, compared to other avian astrovirus sequences, involve the identification of a modified sgRNA sequence situated near the ORF2 start codon, which precedes the ORF1b stop codon. Additionally, the 3' UTR of MP22-196 is shorter than other avian astroviruses. This study expands our understanding of the Avastrovirus 4 clade.

Cross-neutralizing antibody against emerging Omicron subvariants of SARS-CoV-2 in infection-naïve individuals with homologous BNT162b2 or BNT162b2(WT + BA.4/5) bivalent booster vaccination.

Since the emergence of SARS-CoV-2, different variants and subvariants successively emerged to dominate global virus circulation as a result of immune evasion, replication fitness or both. COVID-19 vaccines continue to be updated in response to the emergence of antigenically divergent viruses, the first being the bivalent RNA vaccines that encodes for both the Wuhan-like and Omicron BA.5 subvariant spike proteins. Repeated infections and vaccine breakthrough infections have led to complex immune landscapes in populations making it increasingly difficult to assess the intrinsic neutralizing antibody responses elicited by the vaccines. Hong Kong's intensive COVID-19 containment policy through 2020-2021 permitted us to identify sera from a small number of infection-naïve individuals who received 3 doses of the RNA BNT162b2 vaccine encoding the Wuhan-like spike (WT) and were boosted with a fourth dose of the WT vaccine or the bivalent WT and BA.4/5 spike (WT + BA.4/5). While neutralizing antibody to wild-type virus was comparable in both vaccine groups, BNT162b2 (WT + BA.4/BA.5) bivalent vaccine elicited significantly higher plaque neutralizing antibodies to Omicron subvariants BA.5, XBB.1.5, XBB.1.16, XBB.1.9.1, XBB.2.3.2, EG.5.1, HK.3, BA.2.86 and JN.1, compared to BNT162b2 monovalent vaccine. The single amino acid substitution that differentiates the spike of JN.1 from BA.2.86 resulted in a profound antigenic change.

Reduced Pathogenicity and Transmission Potential of Omicron BA.1 and BA.2 Sublineages Compared with the Early Severe Acute Respiratory Syndrome Coronavirus 2 D614G Variant in Syrian Hamsters.

BACKGROUND: The epidemiological advantage of Omicron variant is evidenced by its rapid spread and the ability to outcompete prior variants. Among Omicron sublineages, early outbreaks were dominated by BA.1, while BA.2 has gained dominance since February 2022. The relative pathogenicity and transmissibility of BA.1 and BA.2 have not been fully defined. METHODS: We compared viral loads and clinical signs in Syrian hamsters after infection with BA.1, BA.2, or D614G variant. A competitive transmission model and next-generation sequencing were used to compare the relative transmission potential of BA.1 and BA.2. RESULTS: BA.1 and BA.2 caused no apparent clinical signs, while D614G caused more than 10% weight loss. Higher viral loads were detected in nasal wash samples and nasal turbinate and lung tissues from BA.1-inoculated hamsters compared with BA.2-inoculated hamsters. No aerosol transmission was observed for BA.1 or BA.2 under the experimental condition in which D614G transmitted efficiently. BA.1 and BA.2 were able to transmit among hamsters via direct contact; however, BA.1 transmitted more efficiently than BA.2 under the competitive transmission model. No recombination was detected from direct contacts exposed simultaneously to BA.1 and BA.2. CONCLUSIONS: Omicron BA.1 and BA.2 demonstrated attenuated pathogenicity and reduced transmission potential in hamsters compared with early SARS-CoV-2 strains.

Slow Waning of Antibodies Following BNT162b2 as a Third Dose in Adults Who Had Previously Received 2 Doses of Inactivated Vaccine.

We administered BNT162b2 as a third dose to 314 adults aged ≥30 years who had previously received 2 doses of inactivated vaccine. We collected blood samples before the third dose and again after 1 month and 6 months, and found robust antibody responses to the ancestral strain at 6 months after receipt of BNT162b2. Antibody responses to Omicron BA.2 by live virus neutralization were weaker after the third dose and had declined to a low level by 6 months.

Immunogenicity of a Third Dose of BNT162b2 to Ancestral Severe Acute Respiratory Syndrome Coronavirus 2 and the Omicron Variant in Adults Who Received 2 Doses of Inactivated Vaccine.

BACKGROUND: Limited data exist on antibody responses to mixed vaccination strategies that involve inactivated coronavirus disease 2019 (COVID-19) vaccines, particularly in the context of emerging variants. METHODS: We conducted an open-label trial of a third vaccine dose of a messenger RNA (mRNA) vaccine (BNT162b2, Fosun Pharma/BioNTech) in adults aged ≥30 years who had previously received 2 doses of inactivated COVID-19 vaccine. We collected blood samples before administering the third dose and 28 days later and tested for antibodies to the ancestral virus using a binding assay (enzyme-linked immunosorbent assay [ELISA]), a surrogate virus neutralization test (sVNT), and a live virus plaque reduction neutralization test (PRNT). We also tested for antibodies against the Omicron variant using live-virus PRNT. RESULTS: In 315 participants, a third dose of BNT162b2 substantially increased antibody titers on each assay. Mean ELISA levels increased from an optical density of 0.3 to 2.2 (P < .001), and mean sVNT levels increased from an inhibition of 17% to 96% (P < .001). In a random subset of 20 participants, the geometric mean PRNT50 titers rose substantially, by 45-fold from day 0 to day 28 against the ancestral virus (P < .001) and by 11-fold against the Omicron variant (P < .001). In daily monitoring, post-vaccination reactions subsided within 7 days for more than 99% of participants. CONCLUSIONS: A third dose of COVID-19 vaccine with an mRNA vaccine substantially improved antibody levels against the ancestral virus and the Omicron variant with a well-tolerated safety profile in adults who had received 2 doses of inactivated vaccine 6 months earlier. CLINICAL TRIALS REGISTRATION: NCT05057182.

Replication of Novel Zoonotic-Like Influenza A(H3N8) Virus in Ex Vivo Human Bronchus and Lung.

Human infection with avian influenza A(H3N8) virus is uncommon but can lead to acute respiratory distress syndrome. In explant cultures of the human bronchus and lung, novel H3N8 virus showed limited replication efficiency in bronchial and lung tissue but had a higher replication than avian H3N8 virus in lung tissue.

Using Functionalized Liposomes to Harvest Extracellular Vesicles of Similar Characteristics in Dermal Interstitial Fluid.

Extracellular vesicles (EVs) are used by living cells for the purpose of biological information trafficking from parental-to-recipient cells and vice versa. This back-and-forth communication is enabled by two distinct kinds of biomolecules that constitute the cargo of an EV: proteins and nucleic acids. The proteomic-cum-genetic information is mediated by the physiological state of a cell (healthy or otherwise) as much as modulated by the biogenesis pathway of the EV. Therefore, in mirroring the huge diversities of human communications, the proteins and nucleic acids involved in cell communications possess seemingly near limitless diversities, and it is this characteristic that makes EVs so highly heterogeneous. Currently, there is no simple and reliable tool for the selective capture of heterogeneous EVs and the delivery of their undamaged cargo for research in extracellular protein mapping and spatial proteomics studies. Our work is a preliminary attempt to address this issue. We demonstrated our approach by using antibody functionalized liposomes to capture EVs from tumor and healthy cell-lines. To characterize their performance, we presented fluorescence and nanoparticle tracking analysis (NTA) results, TEM images, and Western blotting analysis for EV proteins. We also extracted dermal interstitial fluid (ISF) from healthy individuals and used our functionalized synthetic vesicle (FSV) method to capture EVs from their proteins. We constructed three proteomic sets [EV vs ISF, (FSV+EV) vs ISF, and (FSV+EV) vs EV] from the EV proteins and the free proteins harvested from ISF and compared their differentially expressed proteins (DEPs). The performance of our proposed method is assessed via an analysis of 1095 proteins, together with volcano plots, heatmap, GO annotation, and enriched KEGG pathways and organelle localization results of 213 DEPs.

A Survey on Deep Reinforcement Learning Algorithms for Robotic Manipulation.

Robotic manipulation challenges, such as grasping and object manipulation, have been tackled successfully with the help of deep reinforcement learning systems. We give an overview of the recent advances in deep reinforcement learning algorithms for robotic manipulation tasks in this review. We begin by outlining the fundamental ideas of reinforcement learning and the parts of a reinforcement learning system. The many deep reinforcement learning algorithms, such as value-based methods, policy-based methods, and actor-critic approaches, that have been suggested for robotic manipulation tasks are then covered. We also examine the numerous issues that have arisen when applying these algorithms to robotics tasks, as well as the various solutions that have been put forth to deal with these issues. Finally, we highlight several unsolved research issues and talk about possible future directions for the subject.

Novel Zoonotic Avian Influenza A(H3N8) Virus in Chicken, Hong Kong, China.

Zoonotic and pandemic influenza continue to pose threats to global public health. Pandemics arise when novel influenza A viruses, derived in whole or in part from animal or avian influenza viruses, adapt to transmit efficiently in a human population that has little population immunity to contain its onward transmission. Viruses of previous pandemic concern, such as influenza A(H7N9), arose from influenza A(H9N2) viruses established in domestic poultry acquiring a hemagglutinin and neuraminidase from influenza A viruses of aquatic waterfowl. We report a novel influenza A(H3N8) virus in chicken that has emerged in a similar manner and that has been recently reported to cause zoonotic disease. Although they are H3 subtype, these avian viruses are antigenically distant from contemporary human influenza A(H3N2) viruses, and there is little cross-reactive immunity in the human population. It is essential to heighten surveillance for these avian A(H3N8) viruses in poultry and in humans.

Natural Reassortment of Eurasian Avian-Like Swine H1N1 and Avian H9N2 Influenza Viruses in Pigs, China.

Several zoonotic influenza A viruses detected in humans contain genes derived from avian H9N2 subtypes. We uncovered a Eurasian avian-like H1N1 swine influenza virus with polymerase basic 1 and matrix gene segments derived from the H9N2 subtype, suggesting that H9N2 viruses are infecting pigs and reassorting with swine influenza viruses in China.

Recombinant BA.1/BA.2 SARS-CoV-2 Virus in Arriving Travelers, Hong Kong, February 2022.

We studied SARS-CoV-2 genomes from travelers arriving in Hong Kong during November 2021-February 2022. In addition to Omicron and Delta variants, we detected a BA.1/BA.2 recombinant with a breakpoint near the 5' end of the spike gene in 2 epidemiologically linked case-patients. Continued surveillance for SARS-CoV-2 recombinants is needed.

Probable Transmission of SARS-CoV-2 Omicron Variant in Quarantine Hotel, Hong Kong, China, November 2021.

We report detection of severe acute respiratory syndrome coronavirus 2 Omicron variant (B.1.1.529) in an asymptomatic, fully vaccinated traveler in a quarantine hotel in Hong Kong, China. The Omicron variant was also detected in a fully vaccinated traveler staying in a room across the corridor from the index patient, suggesting transmission despite strict quarantine precautions.

Monitoring International Travelers Arriving in Hong Kong for Genomic Surveillance of SARS-CoV-2.

We sequenced ≈50% of coronavirus disease cases imported to Hong Kong during March-July 2021 and identified 70 cases caused by Delta variants of severe acute respiratory syndrome coronavirus 2. The genomic diversity detected in Hong Kong was similar to global diversity, suggesting travel hubs can play a substantial role in surveillance.

Comparison of the immunogenicity of BNT162b2 and CoronaVac COVID-19 vaccines in Hong Kong.

BACKGROUND AND OBJECTIVE: Few head-to-head evaluations of immune responses to different vaccines have been reported. METHODS: Surrogate virus neutralization test (sVNT) antibody levels of adults receiving either two doses of BNT162b2 (n = 366) or CoronaVac (n = 360) vaccines in Hong Kong were determined. An age-matched subgroup (BNT162b2 [n = 49] vs. CoronaVac [n = 49]) was tested for plaque reduction neutralization (PRNT) and spike-binding antibody and T-cell reactivity in peripheral blood mononuclear cells. RESULTS: One month after the second dose of vaccine, BNT162b2 elicited significantly higher PRNT50 , PRNT90 , sVNT, spike receptor binding, spike N-terminal domain binding, spike S2 domain binding, spike FcR binding and antibody avidity levels than CoronaVac. The geometric mean PRNT50 titres in those vaccinated with BNT162b2 and CoronaVac vaccines were 251.6 and 69.45, while PRNT90 titres were 98.91 and 16.57, respectively. All of those vaccinated with BNT162b2 and 45 (91.8%) of 49 vaccinated with CoronaVac achieved the 50% protection threshold for PRNT90. Allowing for an expected seven-fold waning of antibody titres over 6 months for those receiving CoronaVac, only 16.3% would meet the 50% protection threshold versus 79.6% of BNT162b2 vaccinees. Age was negatively correlated with PRNT90 antibody titres. Both vaccines induced SARS-CoV-2-specific CD4+ and CD8+ T-cell responses at 1 month post-vaccination but CoronaVac elicited significantly higher structural protein-specific CD4+ and CD8+ T-cell responses. CONCLUSION: Vaccination with BNT162b2 induces stronger humoral responses than CoronaVac. CoronaVac induces higher CD4+ and CD8+ T-cell responses to the structural protein than BNT162b2.

Waning antibody levels after COVID-19 vaccination with mRNA Comirnaty and inactivated CoronaVac vaccines in blood donors, Hong Kong, April 2020 to October 2021.

The mRNA vaccine Comirnaty and the inactivated vaccine CoronaVac are both available in Hong Kong's COVID-19 vaccination programme. We observed waning antibody levels in 850 fully vaccinated (at least 14 days passed after second dose) blood donors using ELISA and surrogate virus neutralisation test. The Comirnaty-vaccinated group's (n = 593) antibody levels remained over the ELISA and sVNT positive cut-offs within the first 6 months. The CoronaVac-vaccinated group's (n = 257) median antibody levels began to fall below the cut-offs 4 months after vaccination.

SARS-CoV-2 Omicron variant BA.2 neutralisation in sera of people with Comirnaty or CoronaVac vaccination, infection or breakthrough infection, Hong Kong, 2020 to 2022.

BackgroundOmicron subvariant BA.2 circulation is rapidly increasing globally.AimWe evaluated the neutralising antibody response from vaccination or prior SARS-CoV-2 infection against symptomatic infection by BA.2 or other variants.MethodsUsing 50% plaque reduction neutralisation tests (PRNT50), we assessed neutralising antibody titres to BA.2, wild type (WT) SARS-CoV-2 and other variants in Comirnaty or CoronaVac vaccinees, with or without prior WT-SARS-CoV-2 infection. Titres were also measured for non-vaccinees convalescing from a WT-SARS-CoV-2 infection. Neutralising antibodies in BA.2 and BA.1 breakthrough infections and in BA.2 infections affecting non-vaccinees were additionally studied.ResultsIn vaccinees or prior WT-SARS-CoV-2-infected people, BA.2 and BA.1 PRNT50 titres were comparable but significantly (p < 10 - 5) lower than WT. In each group of 20 vaccinees with (i) three-doses of Comirnaty, (ii) two CoronaVac followed by one Comirnaty dose, or (iii) one dose of either vaccine after a WT-SARS-CoV-2 infection, ≥ 19 individuals developed detectable (PRNT50 titre ≥ 10) antibodies to BA.2, while only 15 of 20 vaccinated with three doses of CoronaVac did. Comirnaty vaccination elicited higher titres to BA.2 than CoronaVac. In people convalescing from a WT-SARS-CoV-2 infection, a single vaccine dose induced higher BA.2 titres than three Comirnaty (p = 0.02) or CoronaVac (p = 0.00001) doses in infection-naïve individuals. BA.2 infections in previously uninfected and unvaccinated individuals elicited low (PRNT50 titre ≤ 80) responses with little cross-neutralisation of other variants. However, vaccinees with BA.1 or BA.2 breakthrough infections had broad cross-neutralising antibodies to WT viruses, and BA.1, BA.2, Beta and Delta variants.ConclusionsExisting vaccines can be of help against the BA.2 subvariant.

Postmortem Stability of SARS-CoV-2 in Mouse Lung Tissue.

The infectivity of severe acute respiratory syndrome coronavirus 2 in deceased persons and organisms remains unclear. We studied transgenic K18 hACE2 mice to determine the kinetics of virus infectivity after host death. Five days after death, virus infectivity in the lung declined by >96% and RNA copies declined by 48.2%.

Genetic Diversity of SARS-CoV-2 among Travelers Arriving in Hong Kong.

We sequenced 10% of imported severe acute respiratory syndrome coronavirus 2 infections detected in travelers to Hong Kong and revealed the genomic diversity of regions of origin, including lineages not previously reported from those countries. Our results suggest that international or regional travel hubs might be useful surveillance sites to monitor sequence diversity.