Newcastle disease virus (NDV) belongs to the Avulavirus genus and Paramyxoviridae family virus that causes acute, highly infectious Newcastle disease in poultry. The two proteins of haemagglutinin neuraminidase (HN) and fusion (F) are key virulence factors with an important role in its immunogenicity. Genotype VII NDV is still among the most serious viral hazards to the poultry industry worldwide. In this study, a commercial vector vaccine (HVT-NDV) was evaluated compared to the conventional vaccination strategy against Iranian genotype VII. This experiment showed that the group receiving the conventional vaccination strategy had higher antibodies, fewer clinical signs, and lower viral loads in tracheal swabs and feces. Also, two vaccine groups showed significant difference, which could have resulted from two extra vaccine doses in the conventional group. However, except for antibody levels in commercial chickens in the Iran new-generation vaccine, this difference was minor. Further, both groups showed 100% protection in the challenge study. Despite the phylogenetic gap between the NDV-F gene placed in the vector vaccine and the challenge virus (genotypes I and VII, respectively), the rHVT-NDV vaccine offered strong clinical protection and decreased challenge virus shedding considerably.

OBJECTIVE: To histologically evaluate the effects of a novel human recombinant amelogenin (rAmelX) on periodontal wound healing/regeneration in intrabony defects.
METHODS: Intrabony defects were surgically created in the mandible of three minipigs. Twelve defects were randomly treated with either rAmelX and carrier (test group) or with the carrier only (control group). At 3 months following reconstructive surgery, the animals were euthanized, and the tissues histologically processed. Thereafter, descriptive histology, histometry, and statistical analyses were performed.
RESULTS: Postoperative clinical healing was uneventful. At the defect level, no adverse reactions (eg, suppuration, abscess formation, unusual inflammatory reaction) were observed with a good biocompatibility of the tested products. The test group yielded higher values for new cementum formation (4.81 ± 1.17 mm) compared to the control group (4.39 ± 1.71 mm) without reaching statistical significance (P = .937). Moreover, regrowth of new bone was greater in the test compared to the control group (3.51 mm and 2.97 mm, respectively, P = .309).
CONCLUSIONS: The present results provided for the first-time histologic evidence for periodontal regeneration following the use of rAmelX in intrabony defects, thus pointing to the potential of this novel recombinant amelogenin as a possible alternative to regenerative materials from animal origins.

We evaluated the safety of SCB-2019, a protein subunit vaccine candidate containing a recombinant SARS-CoV-2 spike (S) trimer fusion protein, combined with CpG-1018/alum adjuvants.
This ongoing phase 2/3, double-blind, placebo-controlled, randomized trial is being conducted in Belgium, Brazil, Colombia, the Philippines, and South Africa in participants ≥ 12 years of age. Participants were randomly assigned to receive 2 doses of SCB-2019 or placebo administered intramuscularly 21 days apart. Here, we present the safety results of SCB-2019 over the 6-month period following 2-dose primary vaccination series in all adult participants (≥18 years of age).
A total of 30,137 adult participants received at least one dose of study vaccine (n = 15,070) or placebo (n = 15,067) between 24 March 2021 and 01 December 2021. Unsolicited adverse events, medically-attended adverse events, adverse events of special interest, and serious adverse events were reported in similar frequencies in both study arms over the 6-month follow-up period. Vaccine-related SAEs were reported by 4 of 15,070 SCB-2019 recipients (hypersensitivity reactions in two participants, Bell\'s palsy, and spontaneous abortion) and 2 of 15,067 placebo recipients (COVID-19, pneumonia, and acute respiratory distress syndrome in one participant and spontaneous abortion in the other one). No signs of vaccine-associated enhanced disease were observed.
SCB-2019 administered as a 2-dose series has an acceptable safety profile. No safety concerns were identified during the 6-month follow-up after the primary vaccination.
NCT04672395; EudraCT: 2020-004272-17.

Genotype I of hepatitis B virus (HBV) was proposed recently following sequencing of complete HBV genomes from Vietnam and Laos. However, its long-term molecular evolution is unknown. The objectives of this study were to study the molecular evolution of this genotype from an asymptomatic HBsAg carrier from the Long An cohort over a 15-year period was studied using both NGS and clone-based sequencing. The number of complete genome sequences obtained in 2004, 2007, 2013, and 2019 are 17, 20, 19, and 10, respectively. All strains belong to subgenotype I1, except for six (five from 2007 and one from 2019) and 8 further strains from 2007 which form a cluster branching out from other subgenotype I sequences, supported by a 100% bootstrap value. Based on complete genome sequences, all of the estimated intragroup nucleotide divergence values between these strains and HBV subgenotypes I1-I2 exceed 4%. These strains are recombinants between genotype I1 and subgenotype C but the breakpoints vary. The median intrahost viral evolutionary rate in this carrier was 3.88E-4 substitutions per site per year. The Shannon entropy (Sn) ranged from 0.55 to 0.88 and the genetic diversity, D, ranged from 0.0022 to 0.0041. In conclusion, our data provide evidence of novel subgenotypes. Considering that the 8 strains disappeared after 2007, while one of the 6 strains appears again in 2019, we propose these 6 strains as a new subgenotype, provisionally designated HBV subgenotype I3 and the 8 strains as aberrant genotype.

BACKGROUND: Norovirus (NoV) is the main cause of non-bacterial acute gastroenteritis (AGE) outbreaks worldwide. From September 2015 through August 2018, 203 NoV outbreaks involving 2500 cases were reported to the Shenzhen Center for Disease Control and Prevention.
METHODS: Faecal specimens for 203 outbreaks were collected and epidemiological data were obtained through the AGE outbreak surveillance system in Shenzhen. Genotypes were determined by sequencing analysis. To gain a better understanding of the evolutionary characteristics of NoV in Shenzhen, molecular evolution and mutations were evaluated based on time-scale evolutionary phylogeny and amino acid mutations.
RESULTS: A total of nine districts reported NoV outbreaks and the reported NoV outbreaks peaked from November to March. Among the 203 NoV outbreaks, 150 were sequenced successfully. Most of these outbreaks were associated with the NoV GII.2[P16] strain (45.3%, 92/203) and occurred in school settings (91.6%, 186/203). The evolutionary rates of the RdRp region and the VP1 sequence were 2.1 × 10-3 (95% HPD interval, 1.7 × 10-3-2.5 × 10-3) substitutions/site/year and 2.7 × 10-3 (95% HPD interval, 2.4 × 10-3-3.1 × 10-3) substitutions/site/year, respectively. The common ancestors of the GII.2[P16] strain from Shenzhen and GII.4 Sydney 2012[P16] diverged from 2011 to 2012. The common ancestors of the GII.2[P16] strain from Shenzhen and previous GII.2[P16] (2010-2012) diverged from 2003 to 2004. The results of amino acid mutations showed 6 amino acid substitutions (*77E, R750K, P845Q, H1310Y, K1546Q, T1549A) were found only in GII.4 Sydney 2012[P16] and the GII.2[P16] recombinant strain.
CONCLUSIONS: This study illustrates the molecular epidemiological patterns in Shenzhen, China, from September 2015 to August 2018 and provides evidence that the epidemic trend of GII.2[P16] recombinant strain had weakened and the non-structural proteins of the recombinant strain might have played a more significant role than VP1.

Global HIV-1 genetic diversity forms a major obstacle to the development of an HIV vaccine. It may be necessary to employ subtype-specific HIV-1 vaccines in individual countries according to their HIV-1 subtype distribution. We estimated the global and regional need for subtype-specific HIV-1 vaccines. We took into account the proportions of different HIV-1 variants circulating in each country, the genetic composition of HIV-1 recombinants, and the different genome segments (gag, pol, env) that may be incorporated into vaccines. We modeled different scenarios according to whether countries would employ subtype-specific HIV-1 vaccines against (1) the most common subtype; (2) subtypes contributing more than 5% of HIV infections; or (3) all circulating subtypes. For therapeutic vaccines targeting the most common HIV-1 subtype in each country, 16.5 million doses of subtype C vaccine were estimated globally, followed by subtypes A (14.3 million) and B (4.2 million). A vaccine based on env required 2.6 million subtype E doses, and a vaccine based on pol required 4.8 million subtype G doses. For prophylactic vaccines targeting the most common HIV-1 subtype in each country, 1.9 billion doses of subtype A vaccine were estimated globally, followed by subtype C (1.1 billion) and subtype B (1.0 billion). A vaccine based on env required 1.2 billion subtype E doses, and a vaccine based on pol required 0.3 billion subtype G doses. If subtype-specific HIV-1 vaccines are also directed against less common subtypes in each country, vaccines targeting subtypes D, F, H, and K are also needed and would require up to five times more vaccine doses in total. We conclude that to provide global coverage, subtype-specific HIV-1 vaccines need to be directed against subtypes A, B, and C. Vaccines targeting env also need to include subtype E and those targeting pol need to include subtype G.

UNASSIGNED: Recombinant trivalent influenza vaccine (RIV3) was initially licensed in 2013 and approved for all adults ≥18 in 2014. This study evaluated the safety of RIV3 compared with trivalent standard-dose, inactivated influenza vaccine (IIV3) in Kaiser Permanente Northern California (KPNC).
UNASSIGNED: This Phase 4 observational, postmarketing safety study included persons ≥18 years vaccinated with RIV3 or IIV3 in KPNC during the 2015-2016 influenza season. We compared (1) the rates of prespecified diagnoses of interest (Guillain-Barré Syndrome, pericarditis, pleural effusion, narcolepsy/cataplexy, asthma, acute hypersensitivity reactions, and fever) during various postvaccination risk intervals as well as (2) all-cause hospitalization and mortality 0-180 days after vaccination. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression analyses adjusted for age, sex, race/ethnicity, month of vaccination, and concomitant receipt of other vaccinations.
UNASSIGNED: Comparing the 21 976 persons who received RIV3 with the 283 683 who received IIV3, there were statistically significant differences in the prespecified diagnoses of interest between the 2 groups. Specifically, RIV3 vaccination was associated with fewer fever diagnoses during the 0-41 days postvaccination (OR, 0.38; 95% CI, 0.14-0.86). Also, RIV3 was associated with fewer all-cause hospitalizations during the 0-180 days postvaccination (OR, 0.66; 95% CI, 0.61-0.73), which was mostly related to pregnancy-related hospitalizations in IIV3 recipients. There were no serious adverse events or deaths related to RIV3.
UNASSIGNED: This study did not identify any safety concerns regarding the use of RIV3 in adults.

暂无摘要。

Licensed inactivated influenza vaccines (IIV) are recommended for persons aged ≥65 years, including trivalent high-dose IIV (HD-IIV3) and adjuvanted IIV (aIIV3); both are manufactured in eggs. Quadrivalent recombinant vaccine (RIV4) is produced without eggs. We conducted an exploratory study to compare immunogenicity of HD-IIV3, aIIV3 and RIV4 against cell-grown vaccine and circulating A(H3N2) viruses in 2017-18.
Eighty-nine adults aged 65-74 years participating in a 2-year, open-label immunogenicity trial (ClinicalTrails.gov: NCT02872311) were randomized 1:1:1 to receive HD-IIV3, aIIV3, or RIV4 after receipt of standard dose IIV3 in 2016-17. Serum was obtained at baseline and day 28 post vaccination. Microneutralization titers were determined using four cell-propagated A(H3N2) viruses: 2017-18 vaccine strain (clade 3C.2a), circulating viruses from clades 3C.2a1 and 3C.2a2, and \'antigenically advanced\' clade 3C.3a (2019-20 vaccine strain). Active surveillance was conducted to identify influenza illnesses.
Post vaccination geometric mean titer (GMT) against the vaccine strain was <1:60 in each group and <15% seroconverted. RIV4 generated a greater fold-rise (2.0, 95% CI 1.7-2.5) compared to HD-IIV3 (1.6, 95% CI 1.3-1.8). RIV4 generated higher post vaccination titers against 3C.2a1 and 3C.2a2 viruses, and the mean fold-rise after RIV4 was twice as high (3.3 and 3.5, respectively) relative to HD-IIV3 (1.4 and 1.6) and aIIV3 (1.7 and 1.6). Against the antigenically advanced 3C.3a virus, RIV4 generated a greater mean fold-rise (2.9, 95% CI 2.0-4.3) vs HD-IIV3 (1.3, 95% CI 1.1-1.6) and aIIV3 (1.7, 95% CI 1.3-2.1). Postvaccination titers against 3C.2a2 were ≥1:40 in 5 of 7 participants with PCR-confirmed A(H3N2) infection during the ensuing influenza season.
High-dose, adjuvanted, and recombinant vaccines generated suboptimal neutralizing antibody responses to the cell-grown vaccine strain, but RIV4 generated a greater cross-protective response against circulating and antigenically advanced viruses. Recombinant technology may contribute to more broadly protective influenza vaccines, and comparative effectiveness studies are needed.