Query: Covid-19 vaccine studies pdf

title: Evaluation of the immunogenicity of prime boost vaccination with the replication deficient viral vectored COVID 19 vaccine candidate ChAdOx1 nCoV 19
abstract: Clinical development of the COVID 19 vaccine candidate ChAdOx1 nCoV 19, a replication deficient simian adenoviral vector expressing the full length SARS CoV 2 spike (S) protein was initiated in April 2020 following non human primate studies using a single immunisation. Here, we compared the immunogenicity of one or two doses of ChAdOx1 nCoV 19 in both mice and pigs. Whilst a single dose induced antigen specific antibody and T cells responses, a booster immunisation enhanced antibody responses, particularly in pigs, with a significant increase in SARS CoV 2 neutralising titres.

title: While studies on COVID 19 vaccine is ongoing, the public's thoughts and attitudes to the future COVID 19 vaccine
abstract: In this study, we aim to investigate the thoughts and attitudes of individuals towards the future COVID 19 vaccine.

title: RNA Based COVID 19 Vaccine BNT162b2 Selected for a Pivotal Efficacy Study
abstract: Severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) infections and the resulting disease, coronavirus disease 2019 (COVID 19) have spread to millions of people globally. Multiple vaccine candidates are under development, but no vaccine is currently available.  Healthy adults 18 55 and 65 85 years of age were randomized in an ongoing, placebo controlled, observer blinded dose escalation study to receive 2 doses at 21 day intervals of placebo or either of 2 lipid nanoparticle formulated, nucleoside modified RNA vaccine candidates: BNT162b1, which encodes a secreted trimerized SARS CoV 2 receptor binding domain, or BNT162b2, which encodes a prefusion stabilized membrane anchored SARS CoV 2 full length spike. In each of 13 groups of 15 participants, 12 received vaccine and 3 received placebo. Groups were distinguished by vaccine candidate, age of participant, and vaccine dose level. Interim safety and immunogenicity data of BNT162b1 in younger adults have been reported previously from US and German trials. We now present additional safety and immunogenicity data from the US Phase 1 trial that supported selection of the vaccine candidate advanced to a pivotal Phase 2/3 safety and efficacy evaluation.  In both younger and older adults, the 2 vaccine candidates elicited similar dose dependent SARS CoV 2 neutralizing geometric mean titers (GMTs) comparable to or higher than the GMT of a panel of SARS CoV 2 convalescent sera. BNT162b2 was associated with less systemic reactogenicity, particularly in older adults.  These results support selection of the BNT162b2 vaccine candidate for Phase 2/3 large scale safety and efficacy evaluation, currently underway.

title: Acceptance of a COVID 19 Vaccine in Southeast Asia: A Cross Sectional Study in Indonesia
abstract: Several vaccine candidates are being clinically tested in response to the 2019 coronavirus disease (COVID 19) pandemic. This study was conducted to assess the acceptance of a 50 or 95% effective COVID 19 vaccine, when it becomes available in southeast Asia, among the general population in Indonesia.  A cross sectional online survey was conducted between March 25 and April 6, 2020. Participants were asked if they would accept a free vaccine which was 95 or 50% effective. Using a logistic regression model, we assessed the associations between sociodemographic characteristics, exposure to COVID 19 information, or perceived risk of infection with acceptance of a hypothetical COVID 19 vaccine.  Among 1,359 respondents, 93.3% of respondents (1,268/1,359) would like to be vaccinated for a 95% effective vaccine, but this acceptance decreased to 67.0% (911/1,359) for a vaccine with 50% effectiveness. For a 95% effective vaccine, being a healthcare worker and having a higher perceived risk of COVID 19 infection were associated with higher acceptance, adjusted odds ratio (aOR) 2.01; 95%CI: 1.01, 4.00 and aOR: 2.21; 95%CI: 1.07, 4.59, respectively; compared to civil servants, being retired was associated with less acceptance (aOR: 0.15; 95%CI: 0.04, 0.63) For a 50% effective vaccine, being a healthcare worker was also associated with greater acceptance, aOR: 1.57; 95%CI: 1.12, 2.20.  Acceptance of a COVID 19 vaccine was highly influenced by the baseline effectiveness of the vaccine. Preparing the general population to accept a vaccine with relatively low effectiveness may be difficult.

title: Encouraging results from phase 1/2 COVID 19 vaccine trials
abstract: Dystopian realities generate utopian visions. The dramatic emergence of SARS CoV 2 into our lives and the subsequent COVID 19 pandemic have spawned the active development of nearly 200 vaccine candidates. Science reveals itself to the world in real time in all its glorious uncertainties, but also in all its careful, hardwon, and real achievements. As COVID 19 vaccine trials progress rapidly and with much expectation, two such achievements are published in The Lancet. The results of two early phase COVID 19 vaccine trials are reported, one from investigators at the Jenner Institute at Oxford University (Oxford, UK) with support from AstraZeneca, and the second from investigators supported by CanSino Biologics in Wuhan, China. Both groups used an adenoviral vector, and both report the vaccine achieving humoral responses to the SARS CoV 2 spike glycoprotein receptor binding domain by day 28 as well as T cell responses. Both report local and systemic mild adverse events such as fever, fatigue, and injection site pain. In neither trial was a severe adverse event reported. Andrew Pollard and colleagues report their phase 1/2 randomised trial of one injection of chimpanzee adenovirus vectored COVID 19 vaccine. Vaccine formulation at one concentration was tested against a comparator quadrivalent conjugate meningococcal vaccine among 1077 healthy adults (50% male, 90*9% white) aged 18 55 years (median 35 years, IQR 28 44) recruited from five centres in the UK and followed up for 28 days. Local and systemic adverse events such as fatigue, headache, and local tenderness occurred commonly in COVID 19 vaccinees, but were tolerable and mostly ameliorated by paracetamol. No serious adverse events occurred. Neutralising antibodies were generated in more than 90% of participants across different assays. Responses were sustained up to 56 days of observation. A small non randomly selected, second dose boosted subset showed strong neutralising responses, and few mild adverse events. Importantly, T cell responses were induced in all participants. Wei Chen and colleagues report results from a phase 2 randomised trial of one injection of nonreplicating adenovirus vectored COVID 19 vaccine. Vaccine formulation at two concentrations (ie, 1 x 1011 or 5 x 1010 viral particles per mL) were tested against placebo among 508 healthy COVID 19 unexposed adults (50% male) aged 18 83 years (mean 39*7 years) recruited from one centre in Wuhan, China, and followed up for 28 days. Adverse events such as fever, fatigue, headache, or local site pain occurred by day 28 in 294 (77% of 382 vaccinees and 61 (48% of 126 placebo recipients. Male sex was associated with lower occurrence of fever post vaccination. No serious adverse events occurred. Seroconversion occurred in more than 96% of participants, and neutralising antibodies were generated in about 85% More than 90% had T cell responses. People older than 55 years of age had somewhat lower humoral responses (although still higher than placebo) as did people with previous vector immunity, but these factors did not affect T cell responses. Immunogenicity did not differ by sex. These trial reports are hugely anticipated. The results of both studies augur well for phase 3 trials, where the vaccines must be tested on much larger populations of participants to assess their efficacy and safety. Overall, the results of both trials are broadly similar and promising, notwithstanding differences in the vector, in the geographical locations of the populations studied, and the neutralisation assays used. Without drawing causal inference, the exploration of associations of age and sex with adverse events and immunogenicity reported by Chen and colleagues, and of longevity of response by Pollard and colleagues, are welcomed, given the differential burden of severe outcomes in older adults, and the emerging science around differential Published Online July 20, 2020 https:/doi.org/10.1016/ S0140 6736(20)31611 1

title: Determinants of COVID 19 vaccine acceptance in the US
abstract: The COVID 19 pandemic continues to adversely affect the U.S. which leads globally in total cases and deaths. As COVID 19 vaccines are under development, public health officials and policymakers need to create strategic vaccine acceptance messaging to effectively control the pandemic and prevent thousands of additional deaths.  Using an online platform, we surveyed the U.S. adult population in May 2020 to understand risk perceptions about the COVID 19 pandemic, acceptance of a COVID 19 vaccine, and trust in sources of information. These factors were compared across basic demographics.  Of the 672 participants surveyed, 450 (67% said they would accept a COVID 19 vaccine if it is recommended for them. Males (72% compared to females, older adults =55 years; 78% compared to younger adults, Asians (81% compared to other racial and ethnic groups, and college and/or graduate degree holders (75% compared to people with less than a college degree were more likely to accept the vaccine. When comparing reported influenza vaccine uptake to reported acceptance of the COVID 19 vaccine: 1) participants who did not complete high school had a very low influenza vaccine uptake (10% while 60% of the same group said they would accept the COVID 19 vaccine; 2) unemployed participants reported lower influenza uptake and lower COVID 19 vaccine acceptance when compared to those employed or retired; and, 3) Black Americans reported lower influenza vaccine uptake and lower COVID 19 vaccine acceptance than all other racial groups reported in our study. Lastly, we identified geographic differences with Department of Health and Human Services (DHHS) regions 2 (New York) and 5 (Chicago) reporting less than 50 percent COVID 19 vaccine acceptance.  Although our study found a 67% acceptance of a COVID 19 vaccine, there were noticeable demographic and geographical disparities in vaccine acceptance. Before a COVID 19 vaccine is introduced to the U.S. public health officials and policymakers must prioritize effective COVID 19 vaccine acceptance messaging for all Americans, especially those who are most vulnerable.

title: Safety and immunogenicity of the Ad26.COV2.S COVID 19 vaccine candidate: interim results of a phase 1/2a, double blind, randomized, placebo controlled trial
abstract: The ongoing coronavirus disease (COVID) 19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) might be controlled by an efficacious vaccine. Multiple vaccines are in development, but no efficacious vaccine is currently available.  We designed a multi center phase 1/2a randomized, double blinded, placebo controlled clinical study to assesses the safety, reactogenicity and immunogenicity of Ad26.COV2.S, a non replicating adenovirus 26 based vector expressing the stabilized pre fusion spike (S) protein of SARS CoV 2. Ad26.COV2.S was administered at a dose level of 5x1010 or 1x1011 viral particles (vp) per vaccination, either as a single dose or as a two dose schedule spaced by 56 days in healthy adults (18 55 years old; cohort 1a 1b; n= 402 and healthy elderly >65 years old; cohort 3; n=394) Vaccine elicited S specific antibody levels were measured by ELISA and neutralizing titers were measured in a wild type virus neutralization assay (wtVNA) CD4+ T helper (Th)1 and Th2, and CD8+ immune responses were assessed by intracellular cytokine staining (ICS) RESULTS We here report interim analyses after the first dose of blinded safety data from cohorts 1a, 1b and 3 and group unblinded immunogenicity data from cohort 1a and 3. In cohorts 1 and 3 solicited local adverse events were observed in 58% and 27% of participants, respectively. Solicited systemic adverse events were reported in 64% and 36% of participants, respectively. Fevers occurred in both cohorts 1 and 3 in 19% (5% grade 3) and 4% (0% grade 3) respectively, were mostly mild or moderate, and resolved within 1 to 2 days after vaccination. The most frequent local adverse event (AE) was injection site pain and the most frequent solicited AEs were fatigue, headache and myalgia. After only a single dose, seroconversion rate in wtVNA (50% inhibitory concentration IC50) at day 29 after immunization in cohort 1a already reached 92% with GMTs of 214 (95% CI: 177; 259) and 92% with GMTs of 243 (95% CI: 200; 295) for the 5x1010 and 1x1011vp dose levels, respectively. A similar immunogenicity profile was observed in the first 15 participants in cohort 3, where 100% seroconversion (6/6) (GMTs of 196 [95%CI: 69; 560] and 83% seroconversion (5/6) (GMTs of 127 [95% CI: <58; 327] were observed for the 5x1010 or 1x1011 vp dose level, respectively. Seroconversion for S antibodies as measured by ELISA (ELISA Units/mL) was observed in 99% of cohort 1a participants (GMTs of 528 [95% CI: 442; 630) and 695 (95% CI: 596; 810] for the 5x1010 or 1x1011 vp dose level, respectively, and in 100% (6/6 for both dose levels) of cohort 3 with GMTs of 507 (95% CI: 181; 1418) and 248 (95% CI: 122; 506) respectively. On day 14 post immunization, Th1 cytokine producing S specific CD4+ T cell responses were measured in 80% and 83% of a subset of participants in cohort 1a and 3, respectively, with no or very low Th2 responses, indicative of a Th1 skewed phenotype in both cohorts. CD8+ T cell responses were also robust in both cohort 1a and 3, for both dose levels.  The safety profile and immunogenicity after only a single dose are supportive for further clinical development of Ad26.COV2.S at a dose level of 5x1010 vp, as a potentially protective vaccine against COVID 19.

title: An insight into the epitope based peptide vaccine design strategy and studies against COVID 19
abstract: SARS CoV 2 is a new member of the coronavirus family and caused the pandemic of coronavirus disease 2019 (COVID 19) in 2020. It is crucial to design and produce an effective vaccine for the prevention of rapid transmission and possible deaths wcaused by the disease. Although intensive work and research are being carried out all over the world to develop a vaccine, an effective and approved formulation that can prevent the infection and limit the outbreak has not been announced yet. Among all types of vaccines, epitope based peptide vaccines outshine with their low cost production, easy modification in the structure, and safety. In this review, vaccine studies against COVID 19 have been summarized and detailed information about the epitope based peptide vaccines against COVID 19 has been provided. We have not only compared the peptide vaccine with other types of vaccines but also presented comprehensive literature information about development steps for an effective and protective formulation to give an insight into on going peptide vaccine studies against SARS CoV 2.

title: Zebrafish studies on the vaccine candidate to COVID 19, the Spike protein: Production of antibody and adverse reaction
abstract: Establishing new experimental animal models to assess the safety and immune response to the antigen used in the development of COVID 19 vaccine is an imperative issue. Based on the advantages of using zebrafish as a model in research, herein we suggest doing this to test the safety of the putative vaccine candidates and to study immune response against the virus. We produced a recombinant N terminal fraction of the Spike SARS CoV 2 protein and injected it into adult female zebrafish. The specimens generated humoral immunity and passed the antibodies to the eggs. However, they presented adverse reactions and inflammatory responses similar to severe cases of human COVID 19. The analysis of the structure and function of zebrafish and human Angiotensin converting enzyme 2, the main human receptor for virus infection, presented remarkable sequence similarities. Moreover, bioinformatic analysis predicted protein protein interaction of the Spike SARS CoV 2 fragment and the Toll like receptor pathway. It might help in the choice of future therapeutic pharmaceutical drugs to be studied. Based on the in vivo and in silico results presented here, we propose the zebrafish as a model for translational research into the safety of the vaccine and the immune response of the vertebrate organism to the SARS CoV 2 virus.

title: The need for fast track, high quality and low cost studies about the role of the BCG vaccine in the fight against COVID 19
abstract: Bacillus Calmette Guerin (BCG) vaccination is routine and near universal in many low and middle income countries (LMIC) It has been suggested that BCG can have a protective effect on COVID 19 morbidity and mortality. This commentary discusses the limitations of the evidence around BCG and COVID 19. We argue that higher quality evidence is necessary to understand the protective effect of the BCG vaccine from existing, secondary data, while we await results from clinical trials currently conducted in different settings.