2019 RSV vaccine World Conference: 5 companies including Janssen and Pfizer release clinical results

Respiratory syncytial virus (RSV) can cause upper respiratory tract infection (such as cold like symptoms) and lower respiratory tract infection (such as bronchiolitis and pneumonia), which is the most common cause of bronchiolitis and pneumonia in infants under 1 year old According to who epidemiological data, RSV infection is related to more than 33 million cases of acute lower respiratory tract infection, more than 3 million visits and more than 110000 deaths every year In addition to children, RSV infection also causes a huge burden of disease in the elderly According to the American epidemiological survey, the mortality rate of people over 65 years old due to RSV infection is 7.2 cases / 100000 people every year, and the direct economic burden caused by RSV in the world is more than 80 billion US dollars every year Therefore, RSV has always been the Pearl of the crown in the field of new vaccine research and development, but RSV vaccine has always been known for its high failure rate in clinical research and development In the past decade, RSV vaccine research and development has made rapid progress Products developed based on virus particles, vectors, virus subunits and attenuated vaccines have entered the clinical research and development stage, becoming the focus of the industry This year's RSV vaccine World Conference (rsvww2019) was held in Accra, Ghana, West African country, in November, with the theme of "focusing on new RSV prevention and treatment methods" RSV vaccine World Conference (rsvvw2019) As the most authoritative academic conference in the field of RSV prevention and treatment, rsvvw reports the latest research and development status of RSV vaccine and treatment drugs, epidemiological findings, public health policies, and promotes the progress in the field of RSV infection prevention and control around the world It has always attracted professionals from the pharmaceutical industry, scientific community and epidemic control field all over the world Participants of this meeting include who, bmgf of Gates Foundation, path of International Vaccine organization, NIH of National Institutes of health of the United States and leading commercial companies in the field of international RSV vaccine or antibody research and development The highlight of this meeting is that five commercial companies were invited to release and analyze the clinical research progress and data, including the virus particle vaccine resvax of Novavax, the G protein subunit vaccine bars13 of advacine, the pre-f protein subunit vaccine of Pfizer, and the adenovirus carrier based vaccine of Janssen Some of the most competitive products are ad26.rsv.pref and medi8897 Novavax launched phase III clinical trial in more than 4000 healthy pregnant women in 87 clinical centers in 11 countries at the end of 2015 The primary end point was the prevention effect of maternal immunization strategy on infant lower respiratory tract infection caused by RSV infection, but the final trial did not reach the primary clinical end point, which made the industry deeply regret Novavax presentation At this conference, Novavax team analyzed the sub groups of phase III study and the factors influencing the clinical outcome from multiple perspectives The results show that there are regional differences in vaccine efficacy between South Africa (2422 cases in total) and the United States (1080 cases in total) The reasons for the worse vaccine protection effect in the United States may be related to factors such as immunization timing, basic exposure rate of RSV, breastfeeding rate, etc Novavax said it would further explore the improvement plan in the future Global phase III clinical study design of Novavax RSV vaccine Advacine is the only Chinese company invited to give a keynote speech on clinical progress at this conference At the meeting, its research team announced the results of the first phase I human clinical trial of the self-developed g-protein-based RSV vaccine bars13 in Australia Advacine presentation The highlight of bars13 is that as the world's first RSV vaccine designed for the VED problem, it can use adjuvants to achieve Treg cell regulation, so as to effectively control the inflammatory response caused by the vaccine, and solve the key safety problems of RSV vaccine research and development Design of phase I clinical trial of etifoxine The phase I clinical trial of bars13 was completed in 60 healthy adult volunteers, and each dose group showed good safety and tolerance In terms of immunogenicity, bars13 also showed a good potential After 30 days of vaccination, the level of anti-G protein antibody in each group increased by 3-6 times; 30 days after the second immunization, the level of anti-G protein antibody in the blood of the subjects could further increase by 6-10 times; in terms of the proportion of serological response of the subjects, in the 30 days after immunization, the low-dose group 80-90% of the subjects achieved antibody level conversion, and 100% of the subjects in the high dose group achieved antibody conversion; 30 days after the second immunization, 90% of the subjects in the low dose group achieved antibody conversion, and 100% of the subjects in the high dose group achieved antibody conversion Proportion of antibody serological response of subjects in each group of advacine phase I clinical trial Pfizer has developed a new type of RSV vaccine based on the research results of rsvpref protein of nihd The first phase I / II human clinical trial announced by the conference included more than 1000 subjects, including 18-49 and 50-85 years old healthy people The primary end point was the safety and tolerance of the vaccine, and the secondary end point was the immunogenicity of the vaccine Dr beateschmole Thoma, Pfizer Basic characteristics and target population of Pfizer RSV vaccine The results showed that the vaccine showed good tolerance and safety The main adverse reactions were pain, fatigue and headache at the injection site However, in terms of immunogenicity, there was no significant dose-dependent change in each group The level of neutralizing antibody stimulated by 60 μ g in low dose group was basically the same as that by 240 μ g in high dose group Changes of neutralizing antibody level in Pfizer RSV vaccine phase I / II subjects Janssen announced the design and results of phase IIB clinical trials of its pre RSV vaccine based on adenovirus vector The preliminary study on phase I tolerance and immune efficacy and phase IIa influenza vaccine combination research have been completed before the project This meeting reports the results of recently completed human challenge test Phase II clinical trial design of Janssen ad26.rsv.pref More than 60 healthy subjects were enrolled in the experiment The vaccine was injected on the first day, and the challenge test was carried out on the 28th day, followed by a 6-month follow-up to collect the RSV viral load, antibody level and safety event information of the subjects End point index of protective efficacy of phase IIB clinical vaccine of Janssen ad26.rsv.pref In terms of vaccine efficacy, the end point was the relative protection rate of RSV infection with / without symptoms, and the three sub groups were 37.7%, 45.8% and 51.9% respectively However, due to the wide numerical confidence interval of each index, further research on large samples is needed in the future Since palivizumab was listed on the market, many companies have continued to optimize the neutralization target, antibody metabolism cycle and other aspects to develop new RSV preventive antibodies Medi8897, jointly developed by AstraZeneca and Sanofi, improves the half-life of the product by modifying the FC segment of the antibody, so as to achieve the goal of one injection per RSV epidemic season (called "vaccine like" strategy) The target population of this project is preterm and full-term newborns, children with chronic lung disease or congenital heart disease who enter the first RSV epidemic season These two groups are also high-risk groups of RSV infection AstraZeneca speech At this conference, AstraZeneca reported its phase IIB study, which was carried out in 23 countries, and more than 1400 premature infants (29-35 weeks of gestation) who did not meet the treatment conditions of palivizumab were enrolled The primary end point of the trial was the incidence of lower respiratory tract infection requiring medical treatment within 150 days after immunization (RSV was the cause of infection confirmed by RT-PCR), and the secondary end point included hospitalization rate, safety event, pharmacokinetics, anti drug antibody and pharmacoeconomics Compared with placebo group, the experimental group significantly reduced the incidence of lower respiratory tract infection caused by RSV requiring medical treatment during the follow-up period In terms of safety, the monitoring indicators of adverse reactions in the two groups were basically the same The results of anti drug antibody monitoring showed that at the end of one-year follow-up, the positive rate of placebo group was 1.9%, and that of test group was 3.5%.