Background The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4–12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered. Methods We present data from three single-blind randomised controlled trials—one phase 1/2 study in the UK (COV001), one phase 2/3 study in the UK (COV002), and a phase 3 study in Brazil (COV003)—and one double-blind phase 1/2 study in South Africa (COV005). As previously described, individuals 18 years and older were randomly assigned 1:1 to receive two standard doses of ChAdOx1 nCoV-19 (5 × 10 10 viral particles) or a control vaccine or saline placebo. In the UK trial, a subset of participants received a lower dose (2·2 × 10 10 viral particles) of the ChAdOx1 nCoV-19 for the first dose. The primary outcome was virologically confirmed symptomatic COVID-19 disease, defined as a nucleic acid amplification test (NAAT)-positive swab combined with at least one qualifying symptom (fever ≥37·8°C, cough, shortness of breath, or anosmia or ageusia) more than 14 days after the second dose. Secondary efficacy analyses included cases occuring at least 22 days after the first dose. Antibody responses measured by immunoassay and by pseudovirus neutralisation were exploratory outcomes. All cases of COVID-19 with a NAAT-positive swab were adjudicated for inclusion in the analysis by a masked independent endpoint review committee. The primary analysis included all participants who were SARS-CoV-2 N protein seronegative at baseline, had had at least 14 days of follow-up after the second dose, and had no evidence of previous SARS-CoV-2 infection from NAAT swabs. Safety was assessed in all participants who received at least one dose. The four trials are registered at ISRCTN89951424 (COV003) and ClinicalTrials.gov , NCT04324606 (COV001), NCT04400838 (COV002), and NCT04444674 (COV005). Findings Between April 23 and Dec 6, 2020, 24 422 participants were recruited and vaccinated across the four studies, of whom 17 178 were included in the primary analysis (8597 receiving ChAdOx1 nCoV-19 and 8581 receiving control vaccine). The data cutoff for these analyses was Dec 7, 2020. 332 NAAT-positive infections met the primary endpoint of symptomatic infection more t...

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The prevalence of hepatitis B virus (HBV) infections is a worldwide issue that can lead to both acute and chronic complications with increased morbidity and mortality in affected individuals. Current methods of preventing HBV infections primarily include building patient immunity through administration of hepatitis B vaccinations starting at birth. Certain at-risk individuals, including those with occupational exposure to pathogenic bodily fluids, those who are sexually active or intravenous drug users, are recommended to receive some form of hepatitis B vaccination. The current standard of hepatitis B vaccination in the United States is the Engerix-B vaccine, which consists of a three-dose regimen over a 6-month time period. A new hepatitis B vaccine, Heplisav-B, has been approved for adults in the United States and requires only two doses over 1 month. The unique dosing schedule of Heplisav-B provides the potential for increasing patient compliance and therefore can aid in the effort toward protecting individuals from developing an HBV infection. Results from clinical trials showed that Heplisav-B compared favorably with Engerix-B in safety and efficacy profiles. This paper provides a review of the pharmacology, safety, clinical trials and indications for use for the Heplisav-B vaccine in the United States.

Infection with hepatitis B virus (HBV) continues to be a major problem in the human population. There remains a specific requirement for HBV vaccines capable of circumventing the non-responder/inadequate responder status of some vaccinees. Hepacare has been primarily developed to (1) improve anti-SHBs antibody titres in low responders, to conventional SHBsAg vaccinees, (2) overcome difficulties of non-compliance seen with existing SHBsAg vaccine regimens. Hepacare is a novel recombinant particle produced in eukaryotic cells, consisting of pre-S1, pre-S2 and S proteins of HBV and is adjuvanted with alhydrogel. It has been demonstrated to be highly immunogenic for both B and T cells in mice, chimpanzees and humans and induces higher anti-S ‘a’ determinant antibody titres than SHBsAg vaccines in mice and humans. Hepacare has proven to be at least as efficacious as current SHBsAg vaccines in chimpanzees. Clinical trials in both Europe and the USA have clearly demonstrated its superior ability to induce anti-SHBs antibody seroconversion in low-responder groups, compared with SHBsAg vaccines.

Streptococcus pneumoniae has multiple protein antigens on the surface in addition to the serotype specific polysaccharide capsule antigen. Whilst the capsule antigen is the target of the polysaccharide vaccines, bacterial proteins can also act as targets for the immune system. PnuBioVax (PBV) is being developed as a multi-antigen, serotype-independent prophylactic vaccine against S. pneumoniae disease. In this study we have sought to elucidate the immune response to PBV in immunised rabbits. Sera from PBV immunised rabbits contained high levels of IgG antibodies to the PBV vaccine, and pneumococcal antigens PspA, Ply, PsaA and PiuA which are components of PBV, when compared with control sera. The PBV sera supported killing of the vaccine strain TIGR4 in an opsonophagocytic killing assay and heterologous strains 6B, 19F and 15B. In addition, incubation in PBV sera led to agglutination of several strains of pneumococci, inhibition of Ply-mediated lysis of erythrocytes and reduced bacterial invasion of lung epithelial cells in vitro. These data suggest that PBV vaccination generates sera that has multiple mechanisms of action that may provide effective protection against pneumococcal infection and give broader strain coverage than the current polysaccharide based vaccines.