vaccine
228087117
Safety and Efficacy of the BNT162b2 mRNA Covid 19 Vaccine
Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) infection and the resulting coronavirus disease 2019 (Covid 19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently. Methods In an ongoing multinational, placebo controlled, observer blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 mg per dose) BNT162b2 is a lipid nanoparticle formulated, nucleoside modified RNA vaccine that encodes a prefusion stabilized, membrane anchored SARS CoV 2 full length spike protein. The primary end points were efficacy of the vaccine against laboratory confirmed Covid 19 and safety. Results A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid 19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid 19 (95% credible interval, 90.3 to 97.6) Similar vaccine efficacy (generally 90 to 100% was observed across subgroups defined by age, sex, race, ethnicity, baseline body mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid 19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short term, mild to moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups. Conclusions A two dose regimen of BNT162b2 conferred 95% protection against Covid 19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.
The New England journal of medicine
Fernando P Polack Stephen J Thomas Nicholas R E Kitchin Judith Absalon Alejandra Gurtman Stephen Lockhart John L Perez Gonzalo Perez Marc Edson Duarte Moreira Cristiano A F Zerbini Ruth Bailey Kena A Swanson Satrajit Roychoudhury Kenneth J Koury Ping Li Warren Vincent Kalina David A Cooper Robert W Frenck Laura L Hammitt Ozlem Tureci Haylene Nell Axel Schaefer Serhat Unal Dina B Tresnan Susan H Mather Philip R Dormitzer Ugur Sahin Kathrin U Jansen William C Gruber
215727248
The COVID 19 vaccine development landscape
CoV 2, the coronavirus that causes COVID 19, was published on 11 January 2020, triggering intense global R&D activity to develop a vaccine against the disease. The scale of the humanitarian and economic impact of the COVID 19 pandemic is driving evaluation of nextgeneration vaccine technology platforms through novel paradigms to accelerate development, and the first COVID 19 vaccine candidate entered human clinical testing with unprecedented rapidity on 16 March 2020. The Coalition for Epidemic Preparedness Innovations (CEPI) is working with global health authorities and vaccine developers to support the development of vaccines against COVID 19. To facilitate this effort, we have developed and are continuously maintaining an overview of the global landscape of COVID 19 vaccine development activity. Our landscape database includes vaccine development programmes reported through the WHO's authoritative and continually updated list, along with other projects identified from publicly available and proprietary sources (see Supplementary Box 1) The landscape provides insights into key characteristics of COVID 19 vaccine R&D and serves as a resource for ongoing portfolio management at CEPI. We have also shared our landscape information with others in the global health ecosystem to help improve coordination in the COVID 19 outbreak response and enable global resources and capabilities to be directed towards the most promising vaccine candidates.
Nature Reviews Drug Discovery
Tung Thanh Le Zacharias E Andreadakis Arun Kumar Raul Gomez Roman Stig Tollefsen Melanie K Saville Stephen Mayhew
218533470
Development of an inactivated vaccine candidate for SARS CoV 2
Vaccine candidate tested in monkeys Global spread of severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) has led to an urgent race to develop a vaccine. Gao et al. report preclinical results of an early vaccine candidate called PiCoVacc, which protected rhesus macaque monkeys against SARS CoV 2 infection when analyzed in short term studies. The researchers obtained multiple SARS CoV 2 strains from 11 hospitalized patients across the world and then chemically inactivated the harmful properties of the virus. Animals were immunized with one of two vaccine doses and then inoculated with SARS CoV 2. Those that received the lowest dose showed signs of controlling the infection, and those receiving the highest dose appeared more protected and did not have detectable viral loads in the pharynx or lungs at 7 days after infection. The next steps will be testing for safety and efficacy in humans. Science, this issue p. 77 Preclinical results of an early vaccine candidate that protected rhesus macaque monkeys against SARS CoV 2 infection are presented. The coronavirus disease 2019 (COVID 19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) has resulted in an unprecedented public health crisis. Because of the novelty of the virus, there are currently no SARS CoV 2 specific treatments or vaccines available. Therefore, rapid development of effective vaccines against SARS CoV 2 are urgently needed. Here, we developed a pilot scale production of PiCoVacc, a purified inactivated SARS CoV 2 virus vaccine candidate, which induced SARS CoV 2 specific neutralizing antibodies in mice, rats, and nonhuman primates. These antibodies neutralized 10 representative SARS CoV 2 strains, suggesting a possible broader neutralizing ability against other strains. Three immunizations using two different doses, 3 or 6 micrograms per dose, provided partial or complete protection in macaques against SARS CoV 2 challenge, respectively, without observable antibody dependent enhancement of infection. These data support the clinical development and testing of PiCoVacc for use in humans.
Science
Qiang Gao Linlin Bao Haiyan Mao Kangwei Xu Minnan Yang Yajing Li Ling Zhu Zhe Lv Hong Gao Xiaoqin Ge Biao Kan Yalin Hu Jiangning Liu Fang Cai Deyu Jiang Yanhui Yin Chengfeng Qin Xuejie Gong Xiuyu Lou Dongdong Wu Lang Zhu Wei Deng Yurong Li Jinxing Lu Weidong Yin Yanjun Zhang Chuan Qin
218767206
DNA vaccine protection against SARS CoV 2 in rhesus macaques
Prototype DNA vaccines for SARS CoV 2 The development of a vaccine to protect against severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) is an urgent biomedical need. Yu et al. designed a series of prototype DNA vaccines against the SARS CoV 2 spike protein, which is used by the virus to bind and invade human cells. Analysis of the vaccine candidates in rhesus macaques showed that animals developed protective humoral and cellular immune responses when challenged with the virus. Neutralizing antibody titers were also observed at levels similar to those seen in humans who have recovered from SARS CoV 2 infection. Science, this issue p. 806 Successful protection against SARS CoV 2 in rhesus macaques by means of a prototype DNA vaccine is described. The global coronavirus disease 2019 (COVID 19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) has made the development of a vaccine a top biomedical priority. In this study, we developed a series of DNA vaccine candidates expressing different forms of the SARS CoV 2 spike (S) protein and evaluated them in 35 rhesus macaques. Vaccinated animals developed humoral and cellular immune responses, including neutralizing antibody titers at levels comparable to those found in convalescent humans and macaques infected with SARS CoV 2. After vaccination, all animals were challenged with SARS CoV 2, and the vaccine encoding the full length S protein resulted in >3.1 and >3.7 log10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, as compared with viral loads in sham controls. Vaccine elicited neutralizing antibody titers correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate vaccine protection against SARS CoV 2 in nonhuman primates.
Science
Jingyou Yu Lisa H Tostanoski Lauren Peter Noe B Mercado Katherine McMahan Shant H Mahrokhian Joseph P Nkolola Jinyan Liu Zhenfeng Li Abishek Chandrashekar David R Martinez Carolin Loos Caroline Atyeo Stephanie Fischinger John S Burke Matthew D Slein Yuezhou Chen Adam Zuiani Felipe J N Lelis Meghan Travers Shaghayegh Habibi Laurent Pessaint Alex Van Ry Kelvin Blade Renita Brown Anthony Cook Brad Finneyfrock Alan Dodson Elyse Teow Jason Velasco Roland C Zahn Frank Wegmann Esther A Bondzie Gabriel Dagotto Makda S Gebre Xuan He Catherine Jacob-Dolan Marinela Kirilova Nicole Kordana Zijin Lin Lori F Maxfield Felix Nampanya Ramya Nityanandam John D Ventura Huahua Wan Yongfei Cai Bing Chen Aaron G Schmidt Duane R Wesemann Ralph S Baric Galit Alter Hanne Andersen Mark G Lewis Dan H Barouch
211730278
The SARS CoV 2 Vaccine Pipeline: an Overview
Purpose of Review The goal of this review is to provide a timely overview on efforts to develop a vaccine for the 2019 novel coronavirus SARS CoV 2, the causative agent of coronavirus disease (COVID 19) Recent Findings Previous research efforts to develop a severe acute respiratory syndrome coronavirus (SARS CoV) vaccine in the years following the 2003 pandemic have opened the door for investigators to design vaccine concepts and approaches for the COVID 19 epidemic in China. Both SARS CoV and SARS CoV 2 exhibit a high degree of genetic similarity and bind to the same host cell ACE2 receptor. Based on previous experience with SARS CoV vaccines, it is expected that all COVID 19 vaccines will require careful safety evaluations for immunopotentiation that could lead to increased infectivity or eosinophilic infiltration. Besides this, a COVID 19 vaccine target product profile must address vaccinating at risk human populations including frontline healthcare workers, individuals over the age of 60, and those with underlying and debilitating chronic conditions. Among the vaccine technologies under evaluation are whole virus vaccines, recombinant protein subunit vaccines, and nucleic acid vaccines. Summary Each current vaccine strategy has distinct advantages and disadvantages. Therefore, it is paramount that multiple strategies be advanced quickly and then evaluated for safety and efficacy. Ultimately, the safety studies to minimize undesired immunopotentiation will become the most significant bottleneck in terms of time.
Current Tropical Medicine Reports
Wen-Hsiang Chen Ulrich Strych Peter Jay Hotez Maria Elena Bottazzi
57418573
EPIDEMIOLOGY AND PREVENTION OF VACCINE PREVENTABLE DISEASES
EPIDEMIOLOGY AND PREVENTION OF VACCINE PREVENTABLE DISEASES EPIDEMIOLOGY AND PREVENTION OF VACCINE PREVENTABLE DISEASES khtbkhnh mrkhzy dnshgh `lwm pzshkhy yrn
Edited by William Atkinson
35826307
Vaccine hesitancy: Definition, scope and determinants.
The SAGE Working Group on Vaccine Hesitancy concluded that vaccine hesitancy refers to delay in acceptance or refusal of vaccination despite availability of vaccination services. Vaccine hesitancy is complex and context specific, varying across time, place and vaccines. It is influenced by factors such as complacency, convenience and confidence. The Working Group retained the term 'vaccine' rather than 'vaccination' hesitancy, although the latter more correctly implies the broader range of immunization concerns, as vaccine hesitancy is the more commonly used term. While high levels of hesitancy lead to low vaccine demand, low levels of hesitancy do not necessarily mean high vaccine demand. The Vaccine Hesitancy Determinants Matrix displays the factors influencing the behavioral decision to accept, delay or reject some or all vaccines under three categories: contextual, individual and group, and vaccine/vaccination specific influences.
Vaccine
Noni E MacDonald
25046930
Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults.
BACKGROUND Pneumococcal polysaccharide conjugate vaccines prevent pneumococcal disease in infants, but their efficacy against pneumococcal community acquired pneumonia in adults 65 years of age or older is unknown. METHODS In a randomized, double blind, placebo controlled trial involving 84,496 adults 65 years of age or older, we evaluated the efficacy of 13 valent polysaccharide conjugate vaccine (PCV13) in preventing first episodes of vaccine type strains of pneumococcal community acquired pneumonia, nonbacteremic and noninvasive pneumococcal community acquired pneumonia, and invasive pneumococcal disease. Standard laboratory methods and a serotype specific urinary antigen detection assay were used to identify community acquired pneumonia and invasive pneumococcal disease. RESULTS In the per protocol analysis of first episodes of infections due to vaccine type strains, community acquired pneumonia occurred in 49 persons in the PCV13 group and 90 persons in the placebo group (vaccine efficacy, 45.6% 95.2% confidence interval [CI] 21.8 to 62.5) nonbacteremic and noninvasive community acquired pneumonia occurred in 33 persons in the PCV13 group and 60 persons in the placebo group (vaccine efficacy, 45.0% 95.2% CI, 14.2 to 65.3) and invasive pneumococcal disease occurred in 7 persons in the PCV13 group and 28 persons in the placebo group (vaccine efficacy, 75.0% 95% CI, 41.4 to 90.8) Efficacy persisted throughout the trial (mean follow up, 3.97 years) In the modified intention to treat analysis, similar efficacy was observed (vaccine efficacy, 37.7% 41.1% and 75.8% respectively) and community acquired pneumonia occurred in 747 persons in the PCV13 group and 787 persons in placebo group (vaccine efficacy, 5.1% 95% CI, 5.1 to 14.2) Numbers of serious adverse events and deaths were similar in the two groups, but there were more local reactions in the PCV13 group. CONCLUSIONS Among older adults, PCV13 was effective in preventing vaccine type pneumococcal, bacteremic, and nonbacteremic community acquired pneumonia and vaccine type invasive pneumococcal disease but not in preventing community acquired pneumonia from any cause. (Funded by Pfizer; CAPITA ClinicalTrials.gov number NCT00744263.
The New England journal of medicine
Marc J M Bonten Susanne M Huijts Marieke Bolkenbaas Chris Webber Scott D Patterson Samantha Gault Cornelis H van Werkhoven Anna M M van Deursen Elisabeth A M Sanders Theo J M Verheij Michael Patton Anne McDonough A Moradoghli-Haftvani Helen M Smith Tracey Mellelieu Michael Pride Graham R Crowther Beate Schmoele-Thoma Daniel A Scott Kathrin U Jansen R Lobatto Bas J Oosterman Nils Visser Esther Caspers Andre J Smorenburg Emilio A Emini William C Gruber Diederick E Grobbee
2839926
Efficacy of a tetravalent dengue vaccine in children in Latin America.
BACKGROUND In light of the increasing rate of dengue infections throughout the world despite vector control measures, several dengue vaccine candidates are in development. METHODS In a phase 3 efficacy trial of a tetravalent dengue vaccine in five Latin American countries where dengue is endemic, we randomly assigned healthy children between the ages of 9 and 16 years in a 2:1 ratio to receive three injections of recombinant, live, attenuated, tetravalent dengue vaccine (CYD TDV) or placebo at months 0, 6, and 12 under blinded conditions. The children were then followed for 25 months. The primary outcome was vaccine efficacy against symptomatic, virologically confirmed dengue (VCD) regardless of disease severity or serotype, occurring more than 28 days after the third injection. RESULTS A total of 20,869 healthy children received either vaccine or placebo. At baseline, 79.4% of an immunogenicity subgroup of 1944 children had seropositive status for one or more dengue serotypes. In the per protocol population, there were 176 VCD cases (with 11,793 person years at risk) in the vaccine group and 221 VCD cases (with 5809 person years at risk) in the control group, for a vaccine efficacy of 60.8% (95% confidence interval [CI] 52.0 to 68.0) In the intention to treat population (those who received at least one injection) vaccine efficacy was 64.7% (95% CI, 58.7 to 69.8) Serotype specific vaccine efficacy was 50.3% for serotype 1, 42.3% for serotype 2, 74.0% for serotype 3, and 77.7% for serotype 4. Among the severe VCD cases, 1 of 12 was in the vaccine group, for an intention to treat vaccine efficacy of 95.5% Vaccine efficacy against hospitalization for dengue was 80.3% The safety profile for the CYD TDV vaccine was similar to that for placebo, with no marked difference in rates of adverse events. CONCLUSIONS The CYD TDV dengue vaccine was efficacious against VCD and severe VCD and led to fewer hospitalizations for VCD in five Latin American countries where dengue is endemic. (Funded by Sanofi Pasteur; ClinicalTrials.gov number, NCT01374516.
The New England journal of medicine
Luis Angel Villar Gustavo H Dayan J L Arredondo-garcia Doris Maribel Rivera Rivaldo Venancio da Cunha Carmen C Deseda Humberto Reynales Maria Selma Neves Costa Javier O Morales-Ramirez Gabriel Carrasquilla Luis Carlos Rey Reynaldo Dietze Kleber Giovanni Luz Enrique Rivas Maria Consuelo Miranda Montoya Margarita Cortes Supelano Betzana Zambrano Edith Langevin Mark J Boaz Nadia G Tornieporth Melanie K Saville Fernando R Noriega
4875261
Effect of human rotavirus vaccine on severe diarrhea in African infants.
BACKGROUND Rotavirus is the most common cause of severe gastroenteritis among young children worldwide. Data are needed to assess the efficacy of the rotavirus vaccine in African children. METHODS We conducted a randomized, placebo controlled, multicenter trial in South Africa (3166 infants; 64.1% of the total) and Malawi (1773 infants; 35.9% of the total) to evaluate the efficacy of a live, oral rotavirus vaccine in preventing severe rotavirus gastroenteritis. Healthy infants were randomly assigned in a 1:1:1 ratio to receive two doses of vaccine (in addition to one dose of placebo) or three doses of vaccine the pooled vaccine group or three doses of placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis caused by wild type rotavirus during the first year of life were assessed through active follow up surveillance and were graded with the use of the Vesikari scale. RESULTS A total of 4939 infants were enrolled and randomly assigned to one of the three groups; 1647 infants received two doses of the vaccine, 1651 infants received three doses of the vaccine, and 1641 received placebo. Of the 4417 infants included in the per protocol efficacy analysis, severe rotavirus gastroenteritis occurred in 4.9% of the infants in the placebo group and in 1.9% of those in the pooled vaccine group (vaccine efficacy, 61.2% 95% confidence interval, 44.0 to 73.2) Vaccine efficacy was lower in Malawi than in South Africa (49.4% vs. 76.9% however, the number of episodes of severe rotavirus gastroenteritis that were prevented was greater in Malawi than in South Africa (6.7 vs. 4.2 cases prevented per 100 infants vaccinated per year) Efficacy against all cause severe gastroenteritis was 30.2% At least one serious adverse event was reported in 9.7% of the infants in the pooled vaccine group and in 11.5% of the infants in the placebo group. CONCLUSIONS Human rotavirus vaccine significantly reduced the incidence of severe rotavirus gastroenteritis among African infants during the first year of life. (ClinicalTrials.gov number, NCT00241644.
Malawi medical journal the journal of Medical Association of Malawi
Shabir Ahmed Madhi Nigel A Cunliffe Duncan Steele Desiree Witte Mari Kirsten Cheryl E Louw Bagrey M M Ngwira John C Victor Paul Gillard Brigitte Cheuvart Htay Htay Han Kathleen M Neuzil