A phase 2 randomized controlled dose-ranging trial of recombinant pertussis booster vaccines containing genetically inactivated pertussis toxin in women of childbearing age.

BACKGROUND: A phase 2 randomized-controlled safety and immunogenicity trial evaluating different doses of recombinant acellular pertussis vaccine containing genetically-inactivated pertussis toxin (PTgen) was conducted in women of childbearing age in Thailand to identify formulations to advance to a trial in pregnant women. METHODS: A total of 250 women were randomized 1:1:1:1:1 to receive one dose of one of three investigational vaccines including low-dose recombinant pertussis-only vaccine containing 1 µg PTgen and 1 µg FHA (ap1gen), tetanus, reduced-dose diphtheria (Td) combined to ap1gen (Tdap1gen) or combined to recombinant pertussis containing 2 µg PTgen and 5 µg FHA (Tdap2gen), or one dose of licensed recombinant TdaP vaccine containing 5 µg PTgen and 5 µg FHA (Boostagen®, TdaP5gen) or licensed Tdap vaccine containing 8 µg of chemically inactivated pertussis toxoid (PTchem), 8 µg FHA, and 2.5 µg pertactin (PRN) (BoostrixTM, Tdap8chem). Serum Immunoglobulin G (IgG) antibodies against vaccine antigens were measured before and 28 days after vaccination by ELISA. To advance to a trial in pregnant women, formulations had to induce a PT-IgG seroresponse rate with a 95% confidence interval (95% CI) lower limit of ≥ 50%. RESULTS: Between 5 and 22 July 2018, a total of 250 women with median age of 31 years were enrolled. Post-vaccination PT-IgG seroresponse rates were 92% (95% CI 81-98) for ap1gen, 88% (95% CI 76-95) for Tdap1gen, 80% (95% CI 66-90) for Tdap2gen, 94% (95% CI 83-99) for TdaP5gen, and 78% (95% CI 64-88) for Tdap8chem. Frequencies of injection site and systemic reactions were comparable between the groups. No serious adverse events were reported during the 28-day post-vaccination period. CONCLUSIONS: All recombinant acellular pertussis vaccines were safe and immunogenic in women of childbearing age, and all met pre-defined immunogenicity criteria to advance to a trial in pregnant women. CLINICAL TRIAL REGISTRATION: Thai Clinical Trial Registry, TCTR20180321004.

Antibody persistence 2 and 3 years after booster vaccination of adolescents with recombinant acellular pertussis monovalent aPgen or combined TdaPgen vaccines.

BACKGROUND: Recombinant pertussis vaccines inducing long-lasting immune responses could help to control the rise in pertussis. We here report on persisting antibody responses 2 and 3 years after booster vaccination with a new generation recombinant acellular pertussis vaccine. METHODS: Participants of a phase 2/3 randomised-controlled clinical trial with a monovalent pertussis vaccine containing genetically inactivated pertussis toxin (aPgen) or its tetanus and diphtheria toxoids combination (TdaPgen), or a chemically detoxified comparator vaccine (Tdapchem), (originally conducted between July and August 2015) were invited to participate in observational studies of persisting antibody responses 2 and 3 years after vaccination. Serum IgG against pertussis toxin (PT-IgG) and filamentous hemagglutinin (FHA-IgG) were assessed by ELISA, and PT-neutralising antibodies (PT-Nab) by Chinese Hamster Ovary cell assay. FINDINGS: Waning of antibodies stabilised in aPgen and TdaPgen vaccinees 2 and 3 years after vaccination. Three years post-vaccination PT-neutralising antibodies remained 4·6-fold (95% Confidence Interval (CI) 2·6-8·1) and 3·7-fold (95% CI 2·2-6·1) higher, PT-IgG antibodies 3·0-fold (95% CI 2·2-4·1) and 2·5-fold (95% CI 1·9-3·3) higher, and FHA-IgG antibodies 1·8-fold (95% CI 1·3-2·5) and 1·6-fold (95% CI 1·2-2·1) higher than baseline in aPgen and TdaPgen recipients, respectively. In the Tdapchem group, PT-neutralising and PT-IgG and FHA-IgG antibodies were back at baseline levels 2 years post-vaccination. Three years post-vaccination seroconversion rates for PT-neutralising antibodies were 65·0% (95% CI 44·1-85·9) and 55·0% (95% CI 33·2-76·8) in aPgen and TdaPgen recipients, respectively. INTERPRETATION: Considering the persistence of elevated antibody responses 3 years post-booster vaccination, genetically detoxified monovalent aPgen and TdaPgen vaccines can be expected to induce longer-lasting protection than chemically inactivated Tdap vaccines. FUNDING: BioNet-Asia.

Ancestral Haplotype Retention and Population Expansion Determine the Complicated Population Genetic Structure of the Hilly Lineage of Neolucanus swinhoei Complex (Coleoptera, Lucanidae) on the Subtropical Taiwan Island.

The present study demonstrates that the complicated genetic structure of the hilly lineage of the Neolucanus swinhoei complex was driven by its biological features and habitat requirements as well as hindrance by the CMR during periodical Pleistocene glaciations. The results revealed a tendency of geographical differentiation and major and sub- lineage divergences before and after the Riss glaciation, followed by stable population growth during Würm glaciation. At least four refugia were inferred for N. swinhoei during the Riss-Würm glaciations. The ancestral haplotype retention in the cytochrome oxidase subunit I (COI) gene and compensated substitution in 16S rRNA gene is a possible evolutionary scenario resulting in the inconsistent evolution pattern between COI and 16S rRNA gene coupled with the long-distance dispersal of N. swinhoei. Although the CMR did hinder the dispersal of N. swinhoei, its ancestors may have dispersed to eastern Taiwan through the northern and southern low mountains of the CMR before the Riss glaciation. Our finding suggests that the population growth in the Würm glaciation led a dispersal back to western Taiwan, which is contrast to the more common dispersal scenario from western Taiwan to eastern populations proposed in other studies.

New genera, new species and new records of leafhoppers (Hemiptera: Cicadellidae) from Vietnam.

Recent collecting in northern Vietnam yielded specimens of several new leafhopper species, two of which represent new monotypic genera, and several additional species not previously recorded from Vietnam. The two new genera (Hochiminus n. gen. and Pseudocestius n. gen.) and 15 new species (Abrus digitatus n. sp., Aeternus ninhbinhensis n. sp., Drabescoides bispinosa n. sp., Tenompoella vietnamensis n. sp., Uzelina (Uzelina) vietnamensis sp. n., Hochiminhus tamdaoensis n. sp., Pseudocestius cucphuongensis n. sp., Phlogothamnus pseudorugosus n. sp., Scaphoidella albopunctata n. sp., Bundera onukiiformis n. sp., Carinata arcuata n. sp., Traiguma hamocauda n. sp., Signoretia tamdaoensis n. sp., Amrasca (Quartasca) curvata n. sp., Amrasca (Quartasca) excavata n. sp.) are described and illustrated and comparative notes are provided. An additional 28 species representing 20 genera are newly recorded from Vietnam. Most of the latter were previously recorded only from southern China. The enigmatic species, Tardrabassus pakneunensis Dai Dietrich, previously known from two males collected in Laos in 1918, is newly recorded from Vietnam based on recently collected female specimens. The ovipositor structure of the female confirms placement of Tardrabassus in Iassinae. The female pregenital sternite and ovipositor of Hamulotettix ungulatus Dai Zhang are also illustrated for the first time. A new synonymy is also proposed: Ujna consors Distant, 1908 equals Mileewa puerana Yang Meng, 2010, n. syn.

Enhanced post-licensure safety surveillance of a new recombinant acellular pertussis vaccine licensed as a monovalent (aP, Pertagen®) and tetanus, reduced-dose diphtheria combination (TdaP, Boostagen®) vaccine for immunization of adolescents and adults in Thailand.

A new generation of recombinant acellular pertussis vaccine containing genetically inactivated pertussis toxin (PTgen) was licensed as a monovalent pertussis vaccine (aPgen; Pertagen®) and in combination with tetanus and reduced-dose diphtheria (TdaPgen; Boostagen®) for active immunization in individuals aged 11 years and older in Thailand in 2016. We here report post-marketing safety data on the use of the vaccines in individuals in the community obtained through active pharmacovigilance surveillance including pregnant women participating in a prospective observational study. Between May 2017 and February 2020 for TdaPgen and between June 2018 and February 2020 for aPgen, participating health care providers vaccinated and collected safety data for 11,429 exposed adolescents and adults. This included 1778 pregnant women. The incidence rate of adverse events following immunization (AEFIs) was 11.5 per 1000 of vaccinated individuals (95% confidence interval (95% CI) 9.7-13.6). AEFIs mostly concerned local pain at the injection site and muscle pain, and symptoms were mild and mostly resolved within a few days with no complications. The incidence rate of AEFIs in women vaccinated during pregnancy was 1.1 per 1000 (95% CI 0.3-4.1). Of 833 pregnant women vaccinated with recombinant aPgen or TdaPgen, 91.4% (95% CI 89.3-93.3) had uncomplicated pregnancies and 98.7% (95% CI 97.7-99.4) of the 855 babies delivered by these women were born healthy, which exceeds rates generally reported in Thailand. There were no vaccine-related serious adverse events reported during the surveillance period. In conclusion, active pharmacovigilance confirms that the recombinant pertussis vaccines aPgen (Pertagen) and TdaPgen (Boostagen) are safe in adolescents and adults, including pregnant women vaccinated in the second or third trimester of pregnancy.

New genus and species of Leptopsaltriini (Hemiptera: Cicadidae: Cicadinae) from China and Vietnam, with colour-changing behaviour reported for the first time in Cicadoidea.

One new cicada genus Versicolora gen. nov. and two new species, V. ziyongi sp. nov. from China and V. bellula sp. nov. from China and Vietnam, are described. The new genus is placed in the tribe Leptopsaltriini of the subfamily Cicadinae. The relationship of this new genus to other related taxa is discussed. Versicolora ziyongi sp. nov. camouflages itself on the bark of the host-plants and gradually changes its body colour when captured. This colour-changing behaviour is recorded for the first time in Cicadoidea, which provides innovative information for ecomorphological study of this remarkable species and other cicadas that potentially exhibit this behaviour.

Phylogeography of the cicada Platypleura hilpa in subtropical and tropical East Asia based on mitochondrial and nuclear genes and microsatellite markers.

Climate change and geographical events play key roles in driving population genetic structure of organisms, but different scenarios were suggested for species occurring in tropical and subtropical areas. We investigated the population genetic structure, diversity and demographic history of the cicada Platypleura hilpa which occurs in coastal areas of southern China and northeastern Indo-Burma, and analysed the potential impact of climate change and geological events on its evolutionary history. Our data imply that P. hilpa comprises five main lineages with nearly unique sets of haplotypes and distinct geographic distributions. A major split of the lineages occurred in the Pleistocene. Geographic distance and geomorphic barriers serve as the primary factors shaping the genetic population structure, and several climatic factors are associated with the divergence. The potential range during the Last Glacial Maximum has apparently increased in south China and the exposed South China Sea Shelf. The Pleistocene sea-level fluctuations had profound effects on the regional genetic structure. The Beibu Gulf represents a more important geographic barrier than the Qiongzhou Strait in blocking gene flow among populations. These results contribute to a better understanding of the pressure climatic change and geographical events impose on insects in coastal areas of East Asia.

Heads or tails: exaggerated morphologies in relation to the use of large bamboo internodes in two lizard beetles, Doubledaya ruficollis and Oxylanguria acutipennis (Coleoptera: Erotylidae: Languriinae).

The cavities of bamboos (Poaceae) are used by various animals. Most of the animals access these cavities either by existing cracks or by excavating bamboos with soft walls or small, thin-walled bamboos. Only a few animals excavate into the cavities of large and thick- and hard-walled internodes of mature bamboos. We studied two lizard beetle species (Coleoptera: Erotylidae: Languriinae), Doubledaya ruficollis and Oxylanguria acutipennis, that excavate into large internode cavities of recently dead mature bamboos and have morphological modifications. We observed that females of D. ruficollis used their mandibles to bore oviposition holes on Schizostachyum sp. (mean wall thickness = 3.00 mm) and O. acutipennis did so on Dendrocalamus sp. (3.37 mm) bamboos. Previous studies suggested that the markedly asymmetrical mandibles and needle-like ovipositors of females in the genus Doubledaya are adaptive traits for excavating hard-walled bamboos for oviposition. Therefore, we measured their mandibular lengths and ovipositor lengths. D. ruficollis females had greater asymmetry in the mandibles and shorter and less-sclerotized ovipositors than females of congeners using small bamboos. In contrast, O. acutipennis females had slightly asymmetrical mandibles and elongated, well-sclerotized ovipositors. Oviposition holes of D. ruficollis were cone-shaped (evenly tapering), whereas those of O. acutipennis were funnel-shaped (tube-like at the internal apex). This suggests that D. ruficollis females excavate oviposition holes using the mandibles only, and O. acutipennis females use both the mandibles and ovipositors. These differences suggest different oviposition-associated morphological specialization for using large bamboos: the extremely asymmetrical mandibles in D. ruficollis and elongated, needle-like ovipositors in O. acutipennis.

Boosting Teenagers With Acellular Pertussis Vaccines Containing Recombinant or Chemically Inactivated Pertussis Toxin: A Randomized Clinical Trial.

BACKGROUND: Protection induced by acellular pertussis (aP) vaccines is partial and short-lived, especially in teenagers, calling for novel immunization strategies. METHODS: We conducted an investigator-driven proof-of-concept randomized controlled trial in aP-primed adolescents in Geneva to assess the immunogenicity and reactogenicity of a novel recombinant aP (r-aP) vaccine including recombinant pertussis toxin (PT) and filamentous hemagglutinin (FHA) coadministered with tetanus-diphtheria toxoids (Td), compared to a licensed tetanus-diphtheria-aP vaccine containing chemically detoxified PT (cd/Tdap). The primary immunological endpoints were day 28/365 geometric mean concentrations (GMCs) of total and neutralizing anti-PT antibodies. Memory B cells were assessed. RESULTS: Sixty-two aP-primed adolescents were randomized and vaccinated with r-aP + Td or cd/Tdap. Reactogenicity, adverse events, and baseline GMCs were similar between the groups. Day 28 PT-neutralizing GMCs were low after cd/Tdap (73.91 [95% confidence interval {CI}, 49.88-109.52] IU/mL) and approximately 2-fold higher after r-aP + Td (127.68 [95% CI, 96.73-168.53] IU/mL; P = .0162). Anti-PT GMCs were also low after cd/Tdap (52.43 [95% CI, 36.41-75.50] IU/mL) and 2-fold higher after r-aP + Td (113.74 [95% CI, 88.31-146.50] IU/mL; P = .0006). Day 28 anti-FHA GMCs were similar in both groups. Day 365 anti-PT (but not PT-neutralizing) GMCs remained higher in r-aP + Td vaccinees. PT-specific memory B cells increased significantly after r-aP + Td but not cd/Tdap boosting. CONCLUSIONS: Boosting aP-primed adolescents with r-aP induced higher anti-PT and PT-neutralizing responses than cd/Tdap and increased PT-specific memory B cells. Despite this superior immunogenicity, r-aP may have to be given repeatedly, earlier, and/or with novel adjuvants to exert an optimal influence in aP-primed subjects. CLINICAL TRIALS REGISTRATION: NCT02946190.

Descriptions of four new species of Bactrocera and new country records highlight the high biodiversity of fruit flies in Vietnam (Diptera, Tephritidae, Dacinae).

Recent snap-shot surveys for fruit flies in Vietnam in 2015 and 2017 using traps baited with the male Dacinae fruit fly lures methyl eugenol, cue-lure and zingerone, collected 56 species, including 11 new country records and another 11 undescribed species, four of which are described in this paper. This increases the number of described species known to occur in Vietnam from 78 to 93. Species accumulation curves, based on the Chao 2 mean estimate, suggest that we collected 60-85 % of the local fauna at the sites sampled, and that species diversity decreases with increasing latitude. The four new species are named: Bactrocera (Tetradacus) ernesti Leblanc & Doorenweerd sp. n., B. (Asiadacus) connecta Leblanc & Doorenweerd sp. n., B. (Parazeugodacus) clarifemur Leblanc & Doorenweerd sp. n., and B. (Bactrocera) adamantea Leblanc & Doorenweerd sp. n. In addition to morphological data COI DNA sequence data of both the COI-5P and COI-3P mitochondrial DNA gene regions is provided. Three of the four newly described species are morphologically and genetically easily distinguished from all other members of Dacini. Bactroceraclarifemur sp. n. is superficially similar to B.pendleburyi (Perkins) based on morphology, but there are several apomorphic characters to distinguish the two. Both COI and a segment of the nuclear gene Elongation Factor 1 alpha separate the two species as well.

A new species of the genus Mecistoscelis Reuter from Vietnam (Hemiptera: Miridae: Mecistoscelini), with key to Mecistoscelis species.

A new species, Mecistoscelis lansburyi Kim et Jung sp. nov. is described from Vietnam. Diagnosis, description including genitalia, and biological notes are presented with illustrations and photographs. The photographic image of female genital structure of this tribe is first presented based on M. lansburyi sp. nov. and key to the Mecistoscelis species is provided.

Antibody persistence after vaccination of adolescents with monovalent and combined acellular pertussis vaccines containing genetically inactivated pertussis toxin: a phase 2/3 randomised, controlled, non-inferiority trial.

BACKGROUND: The immunogenicity of acellular pertussis vaccines and persistence of immunity after vaccination might be improved by using genetically inactivated pertussis toxin (PTgen) instead of chemically inactivated pertussis toxin (PTchem) because of the preservation of conformational epitopes. We assessed the safety and immunogenicity of two vaccines containing PTgen 1 year after vaccination. METHODS: We did a phase 2/3 non-inferiority, randomised, controlled trial involving 450 adolescents (age 12-17 years) enrolled between July 6, 2015, and Aug 20, 2015. Participants were randomised 1:1:1 to receive one dose of vaccine containing PTgen and filamentous haemagglutinin (FHA) either in a monovalent formulation (aP[PTgen/FHA]) or in a combined formulation with tetanus and reduced-dose diphtheria toxoids (TdaP[PTgen/FHA]) or to receive a commercial vaccine containing reduced-dose PTchem (Tdap) as a comparator. We report a secondary trial outcome, namely antibody persistence 1 year after vaccination, assessed per protocol in 150 randomly preselected participants (50 per group). Seroconversion was defined as antibody titres at least four times greater than at baseline. Safety was assessed in all trial participants. This study is registered in the Thai Clinical Trial Registry, number TCTR20150703002. FINDINGS: Between June 5, 2016, and Aug 9, 2016, 442 (98%) of 450 enrolled participants attended a 1-year follow-up visit. After 1 year, persistent seroconversion for pertussis toxin neutralising antibodies was seen in 38 (76%, 95% CI 64-88) participants in the aP(PTgen/FHA) group and 41 (81%, 70-92) in the TdaP(PTgen/FHA) group, but in only four (8%, 1-16) in the Tdap comparator group. Seroconversion rates for IgG antibodies against pertussis toxin and FHA were also greater in the aP(PTgen/FHA) group (82%, 95% CI 71-93 and 64%, 51-77, respectively) and TdaP(PTgen/FHA) group (75%, 63-87 and 56%, 42-70, respectively) than in the Tdap group (4%, 0-9, p<0·0001, and 28%, 16-41, p=0·0007, respectively). 13 serious adverse events were reported in 12 participants and all were judged to be unrelated to the study vaccines. Five pregnancies were reported during follow-up, none of which had any maternal or neonatal complications. INTERPRETATION: A monovalent and a combined recombinant acellular pertussis vaccine containing PTgen induced antibody responses that were greater and sustained for longer than those achieved with the Tdap comparator vaccine. New recombinant pertussis vaccines containing PTgen might offer new opportunities to limit pertussis resurgence and can be widely used, including in pregnant women. FUNDING: BioNet-Asia.

New species and new records of Tingidae (Insecta: Heteroptera) from Vietnam.

In the frame of recent field collecting surveys, four species of Tingidae (Insecta: Heteroptera) new to Vietnam are recorded and three species new to science are described, namely Nectocader vietnamensis, Cetiothucha constanti, and Oncophysa hae. The diversity and richness of Vietnamese Tingidae is discussed, considering the locations visited versus the number of species discovered.

New species of Callichromatini Swainson, 1840. (Coleoptera, Cerambycidae). New Cerambycidae from Vietnam. Part 6.

Three new species of Cerambycidae, Callichromatini from Vietnam are described: Aphrodisium lingafelteri sp. nov., Mimochelidonium vietnamicum sp. nov., and Polyzonus (Striatopolyzonus) tonkinensis sp. nov. The genus Mimochelidonium Bentanachs & Drouin is recorded as new for the fauna of Vietnam.

Descriptions of four new species of Semia Matsumura (Hemiptera: Cicadidae: Psithyristriini) from Vietnam, with a key to the species of Semia.

This paper provides descriptions of four new species of the genus Semia Matsumura, 1917 from Vietnam: Semia magna sp. nov., Semia spiritus sp. nov., Semia pallida sp. nov., and Semia albusequi sp. nov. A key to the 13 species of Semia is provided.

Taxonomic review of the Genus Tautoneura Anufriev (Hemiptera: Auchenorrhyncha: Cicadellidae: Typhlocybinae) from Korea, with description of one new species.

One new species of the genus Tautoneura, T. polymitusa sp. nov., is described, and T. tricolor Anufriev, 1969 and T. japonica (Dworakowska, 1972) are reported from Korea for the first time. Descriptions, illustrations and a key to the Korean Tautoneura species are provided.

New species of the genus Mahinda Krombein, 1983 (Hymenoptera, Chrysididae, Amiseginae).

Three new species of Mahinda are described, bo from Vietnam, borneensis from Malaysian Borneo and sulawesiensis from northern Sulawesi. A key to the three known species is provided including the previously described species, saltator Krombein, 1983.

Discovery of the genus Formosiepyris Terayama, (Hymenoptera, Bethylidae) in Vietnam, with a description of a new species.

Formosiepyrisvietnamensis sp. n. (Hymenoptera: Bethylidae) is described based on material collected from Da Lat, southern Vietnam. This is the first record of Formosiepyris Terayama from Vietnam. The new species can be distinguished from other Formosiepyris species by a narrow and rounded clypeus; a mandible with three teeth; a second metasomal tergite having small, sparsely distributed punctures and smooth interspaces, except for anterior 2/5, which is microreticulate; and a head length : width aspect ratio of 10 : 11. A key to the Oriental species of Formosiepyris is provided.

Needle-free and adjuvant-free epicutaneous boosting of pertussis immunity: Preclinical proof of concept.

The limited durability of pertussis vaccine-induced protection requires novel approaches to reactivate immunity and limit pertussis resurgence in older children and adults. We propose that periodic boosters could be delivered using a novel epicutaneous delivery system (Viaskin) to deliver optimized pertussis antigens such as genetically-detoxified pertussis toxin (rPT). To best mimic the human situation in which vaccine-induced memory cells persist, whereas antibodies wane, we developed a novel adoptive transfer murine model of pertussis immunity. This allowed demonstrating that a single application of Viaskin delivering rPT and/or pertactin and filamentous hemagglutinin effectively reactivates vaccine-induced pertussis immunity and protects against Bordetella pertussis challenge. Recalling pertussis immunity without needles nor adjuvant may considerably facilitate the acceptance and application of periodic boosters.

Cicada genus Pomponia Stål, 1866 (Hemiptera: Cicadidae) from Vietnam and Cambodia, with a new species, a new record, and a key to the species.

The genus Pomponia Stål, 1866 from Vietnam and Cambodia is reviewed . Pomponia brevialata Lee & Pham, sp. nov. is described from Vietnam. Pomponia backanensis Pham & Yang, 2009 is added to the Cambodian cicada fauna. A key to the seven Vietnamese and Cambodian species of the genus Pomponia Stål, 1866 is provided: P. linearis (Walker, 1850), P. backanensis Pham & Yang, 2009, P. brevialata Lee & Pham, sp. nov., P. subtilita Lee, 2009, P. piceata Distant, 1905, P. daklakensis Sanborn, 2009, and P. orientalis (Distant, 1912). Synonymic lists, information on geographical distributions, and material examined for the Vietnamese and Cambodian species of Pomponia are provided.