Notes

Evaluation of the Z-score accuracy associated with noninvasive pre-natal assessment with regard to baby trisomies 12, 18 and 21 in a single center.
[This retracts the article DOI 10.5001/omj.2013.59.].
We sought to assess the prevalence of hepatitis B virus (HBV) seroprotection among vaccinated children in the Assiut governorate, Egypt, and assess a booster dose immune memory response among non-seroprotected children.

Using a multistage cluster sample, 566 children were recruited from three clusters one urban and two rural. Children were aged from nine months to 16 years old. All participants received the full three doses of the compulsory HBV vaccine during infancy. Serum hepatitis B surface antigen (HBsAg), total anti-hepatitis B core (anti-HBc) antibodies, and quantitative detection of anti-HBs were measured using enzyme-linked immunosorbent assay. Repeatedly positive samples for HBsAg/anti-HBc were submitted for quantitative HBV DNA detection using real-time polymerase chain reaction. Non-seroprotective participants (anti-HBs < 10 IU/L) were given a booster dose of HBV vaccine. Two weeks later, a blood sample was taken from each child to assess an anamnestic response.

The seroprotection rate ware-booster undetectable anti-HBs titers may be unable to develop anamnestic response, and a second vaccination series might be necessary for HBV protection for these children.
Older age of children was the only significant predictor for HBV non-seroprotection. High anamnestic response rate signifies the presence of immune memory with long-term protection despite the waning of anti-HBs over time. However, some children with pre-booster undetectable anti-HBs titers may be unable to develop anamnestic response, and a second vaccination series might be necessary for HBV protection for these children.Chikungunya virus (CHIKV), which causes a febrile illness characterized by severe and prolonged polyarthralgia/polyarthritis, is responsible for a global disease burden of millions of cases each year with autochthonous transmission in over 100 countries and territories worldwide. There is currently no approved treatment or vaccine for CHIKV. One live-attenuated vaccine (LAV) developed by the United States Army progressed to Phase II human clinical trials but was withdrawn when 8% of volunteers developed joint pain associated with vaccination. Attenuation of the Army's CHIKV LAV strain 181 clone 25 (CHIKV-181/25) relies on two mutations in the envelope 2 (E2) glycoprotein responsible for cell binding and entry, making it particularly prone to reversion, a common concern for replication-competent vaccines. High error rates associated with RNA virus replication have posed a challenge for LAV development where stable incorporation of attenuating elements is necessary for establishing safety in pre-clinical models. Herein, we incorporate two replicase mutations into CHIKV-181/25 which modulate CHIKV replication fidelity combined with additional attenuating features that cannot be eliminated by point mutation. The mutations were stably incorporated in the LAV and did not increase virulence in mice. Two fidelity-variant CHIKV LAVs generated neutralizing antibodies and were protective from CHIKV disease in adult mice. Unexpectedly, our fidelity-variant candidates were more mutable than CHIKV-181/25 and exhibited restricted replication in mice and Aedes mosquitoes, a possible consequence of hypermutation. Our data demonstrate safety and efficacy but highlight a further need to evaluate fidelity-altering phenotypes before use as a LAV given the potential for virulent reversion.The 'D614G' mutation (Aspartate-to-Glycine change at position 614) of the SARS-CoV-2 spike protein has been speculated to adversely affect the efficacy of most vaccines and countermeasures that target this glycoprotein, necessitating frequent vaccine matching. Virus neutralisation assays were performed using sera from ferrets which received two doses of the INO-4800 COVID-19 vaccine, and Australian virus isolates (VIC01, SA01 and VIC31) which either possess or lack this mutation but are otherwise comparable. Through this approach, supported by biomolecular modelling of this mutation and the commonly-associated P314L mutation in the RNA-dependent RNA polymerase, we have shown that there is no experimental evidence to support this speculation. We additionally demonstrate that the putative elastase cleavage site introduced by the D614G mutation is unlikely to be accessible to proteases.One-third of world's population is predicted to be infected with tuberculosis (TB). The resurgence of this deadly disease has been inflamed by comorbidity with human immunodeficiency virus (HIV). The risk of TB in people living with HIV (PLWH) is 15-22 times higher than people without HIV. Development of a single vaccine to combat both diseases is an ardent but tenable ambition. Studies have focused on the induction of specific humoral and cellular immune responses against HIV-1 following recombinant BCG (rBCG) expressing HIV-1 antigens. Recent advances in the TB vaccines led to the development of promising candidates such as MTBVAC, the BCG revaccination approach, H4IC31, H56IC31, M72/AS01 and more recently, intravenous (IV) BCG. Modification of these vaccine candidates against TB/HIV coinfection could reveal key correlates of protection in a representative animal model. This review discusses the (i) potential TB vaccine candidates that can be exploited for use as a dual vaccine against TB/HIV copandemic (ii) progress made in the realm of TB/HIV dual vaccine candidates in small animal model, NHP model, and human clinical trials (iii) the failures and promising targets for a successful vaccine strategy while delineating the correlates of vaccine-induced protection.Simian adenoviral and modified vaccinia Ankara (MVA) viral vectors used in heterologous prime-boost strategies are potent inducers of T cells against encoded antigens and are in advanced testing as vaccine carriers for a wide range of infectious agents and cancers. It is unclear if these responses can be further enhanced or sustained with reboosting strategies. Furthermore, despite the challenges involved in MVA manufacture dose de-escalation has not been performed in humans. In this study, healthy volunteers received chimpanzee-derived adenovirus-3 and MVA vaccines encoding the non-structural region of hepatitis C virus (ChAd3-NSmut/MVA-NSmut) 8 weeks apart. Volunteers were then reboosted with a second round of ChAd3-NSmut/MVA-NSmut or MVA-NSmut vaccines 8 weeks or 1-year later. We also determined the capacity of reduced doses of MVA-NSmut to boost ChAd3-NSmut primed T cells. Reboosting was safe, with no enhanced reactogenicity. Reboosting after an 8-week interval led to minimal re-expansion of transgene-specific T cells. However, after a longer interval, T cell responses expanded efficiently and memory responses were enhanced. The 8-week interval regimen induced a higher percentage of terminally differentiated and effector memory T cells. Reboosting with MVA-NSmut alone was as effective as with ChAd3-NSmut/MVA-NSmut. A ten-fold lower dose of MVA (2 × 107pfu) induced high-magnitude, sustained, broad, and functional Hepatitis C virus (HCV)-specific T cell responses, equivalent to standard doses (2 × 108 pfu). Overall, we show that following Ad/MVA prime-boost vaccination reboosting is most effective after a prolonged interval and is productive with MVA alone. Importantly, we also show that a ten-fold lower dose of MVA is as potent in humans as the standard dose.[This corrects the article DOI 10.1038/s41541-020-0179-4.].Malaria remains one of the world's most urgent global health problems, with almost half a million deaths and hundreds of millions of clinical cases each year. Existing interventions by themselves will not be enough to tackle infection in high-transmission areas. The best new intervention would be an effective vaccine; but the leading P. falciparum and P. vivax vaccine candidates, RTS,S and VMP001, show only modest to low field efficacy. New antigens and improved ways for screening antigens for protective efficacy will be required. This study exploits the potential of Virus-Like Particles (VLP) to enhance immune responses to antigens, the ease of coupling peptides to the Q beta (Qβ) VLP and the existing murine malaria challenge to screen B-cell epitopes for protective efficacy. We screened P. vivax TRAP (PvTRAP) immune sera against individual 20-mer PvTRAP peptides. The most immunogenic peptides associated with protection were loaded onto Qβ VLPs to assess protective efficacy in a malaria sporozoite challenge. A second approach focused on identifying conserved regions within known sporozoite invasion proteins and assessing them as part of the Qβ. Using this VLP as a peptide scaffold, four new protective B-cell epitopes were discovered three from the disordered region of PvTRAP and one from Thrombospondin-related sporozoite protein (TRSP). Antigenic interference between these and other B-cell epitopes was also explored using the virus-like particle/peptide platform. This approach demonstrates the utility of VLPs to help identifying new B-cell epitopes for inclusion in next-generation malaria vaccines.Development of effective preventative interventions against SARS-CoV-2, the etiologic agent of COVID-19 is urgently needed. The viral surface spike (S) protein of SARS-CoV-2 is a key target for prophylactic measures as it is critical for the viral replication cycle and the primary target of neutralizing antibodies. We evaluated design elements previously shown for other coronavirus S protein-based vaccines to be successful, e.g., prefusion-stabilizing substitutions and heterologous signal peptides, for selection of a S-based SARS-CoV-2 vaccine candidate. In vitro characterization demonstrated that the introduction of stabilizing substitutions (i.e., furin cleavage site mutations and two consecutive prolines in the hinge region of S2) increased the ratio of neutralizing versus non-neutralizing antibody binding, suggestive for a prefusion conformation of the S protein. Furthermore, the wild-type signal peptide was best suited for the correct cleavage needed for a natively folded protein. These observations translated into superior immunogenicity in mice where the Ad26 vector encoding for a membrane-bound stabilized S protein with a wild-type signal peptide elicited potent neutralizing humoral immunity and cellular immunity that was polarized towards Th1 IFN-γ. This optimized Ad26 vector-based vaccine for SARS-CoV-2, termed Ad26.COV2.S, is currently being evaluated in a phase I clinical trial (ClinicalTrials.gov Identifier NCT04436276).Implementation of a vaccine is likely the best approach to curtail Chlamydia trachomatis infections. The aim of this study was to determine the ability of a vaccine formulated with the recombinant major outer membrane protein (MOMP) and Th1 and Th2 adjuvants, delivered by combinations of systemic and mucosal routes, to elicit long-term protection in mice against a genital challenge with Chlamydia muridarum. As a negative control, mice were vaccinated with the recombinant Neisseria gonorrhoeae porinB, and the positive control group was immunized with C. muridarum live elementary bodies (EB). The four vaccines formulated with MOMP, as determined by the titers of IgG and neutralizing antibodies in serum, proliferative responses of T-cells stimulated with EB and levels of IFN-γ in the supernatants, elicited robust humoral and cellular immune responses over a 6-month period. Groups of mice were challenged genitally at 60, 120, or 180 days postimmunization. Based on the number of mice with positive vaginal cultures, number of positive cultures, length of time of shedding, and number of inclusion forming units recovered, MOMP vaccinated groups were significantly protected.
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