INTERNATIONAL SOS WEEKLY SCIENTIFIC UPDATE
In this edition, Dr Doug from International SOS shares the very latest insights on the development of COVID immunity and vaccine development. Vaccine Development & Approval / AstraZeneca and Johnson & Johnson to resume us vaccine trialsFDA COVID-19 vaccine process is “thoughtful and deliberate”AstraZeneca’s COVID-19 vaccine follows genetic instructionsPfizer is now including teens in clinical trials for its COVID-19 vaccine Novavax delays US trial of COVID-19 vaccine to NovemberInfo graphic on COVID-19 vaccine developmentWhat defines an efficacious COVID-19 vaccine? Vaccine Distribution / Brazil approves import of China’s Sinovac vaccineGerman Health Minister expects a COVID vaccine will be available early 2021Lancet article reviews UK vaccine planning Outbreaks and Epidemiology / Melbourne begins easing lockdown Immune Response / Oxford vaccine prompts immune response in elderlyTwo studies show long-term COVID-19 immune responsePre-print showing waning antibodies & Responses from two scientistsTwo thirds of US teens fail to get needed vaccines AstraZeneca and Johnson & Johnson to resume us vaccine trials AstraZeneca and Johnson & Johnson have been given approval by the FDA (US Food and Drug Administration) to restart their Phase 3 trials in the US. AstraZeneca, one of the leading vaccine developers, paused its US trial on 6 September after a report of a serious neurological illness, believed to be transverse myelitis, in a participant in the company’s UK trial. Trials had resumed in all countries except the US. Johnson & Johnson paused all of its large, late-stage trial on 12 October after a study participant became ill. FDA COVID-19 vaccine process is “thoughtful and deliberate” Dr. Mark McClellan, former FDA Commissioner under President George W. Bush, observed Thursday’s FDA advisory panel on COVID-19 vaccine research, where independent experts offered advice on the way forward. McClellan told NPR’s Morning Edition that after Thursday’s advisory meeting, Americans should feel confident in the FDA’s approach toward a vaccine. “’I think people for the most part – the experts, the others listening – found it very reassuring to know that even though FDA is going fast, it’s not cutting corners. And it’s trying to be very thoughtful and deliberate about getting the evidence needed before the vaccine becomes available — even the people in the highest risk groups, like health care workers and people living in nursing homes’, McLellan said.” AstraZeneca’s COVID-19 vaccine follows genetic instructions AstraZeneca’s / Oxford COVID-19 vaccine accurately follows the genetic instructions programmed into it by its developers to successfully provoke a strong immune response, according to a detailed analysis carried reported by Oxford University on 22 October 2020. “The vaccine is doing everything we expected and that is only good news in our fight against the illness,” said David Matthews, an expert in virology from Bristol University, who led the research. Pfizer is now including teens in clinical trials for its COVID-19 vaccine Pfizer is now including teens in clinical trials for its COVID-19 vaccine candidate, expanding the participation age to include high schoolers and middle schoolers, according to USA Today. Pfizer is the only pharmaceutical company allowing minors to join coronavirus vaccine trials at the moment. The company initially lowered the age to 16, and this week, Cincinnati Children’s Hospital Medical Center vaccinated the first 12-year-old. Vaccine experts and pediatricians have voiced mixed reactions, USA Today reported. Some say drug manufacturers should wait until the vaccines have been approved in adults, but others say it’s necessary to proceed with vaccine testing among specific groups, including minors. Novavax delays US trial of COVID-19 vaccine to November Novavax announced on 28 October 2020 that it has delayed the start of Phase 3 US trials of its coronavirus vaccine until the end of November, blaming delays in scaling up the manufacturing process. Novavax has a Phase 3 a trial running in the UK which has expanded to 15,000 volunteers. The North American trials, to be conducted with the support of “Operation Warp Speed,” is looking to enrol 30,000 volunteers in the US and Mexico. Novavax is the leader in producing a “subunit vaccine” which contains viral proteins but no RNA or DNA. Infographic on COVID-19 vaccine development The Wall Street Journal has released this excellent graphic of COVID-19 vaccine development: Row 1 describes the four main types of vaccines. Rows 2,3 and 4 shows significant dates for the nine leading vaccine candidates. What defines an efficacious COVID-19 vaccine? Some countries have begun deploying COVID-19 vaccines on the strength of immunogenicity, the ability of a vaccine to invoke an immune response. An article in The Lancet (27 October) notes that “the goal of vaccine development is to gain direct evidence of vaccine efficacy (the ability to prevent or reduce the severity of infections) in protecting humans against SARS-CoV-2.” The article also notes that “the most important efficacy endpoint, protection against severe disease and death, is difficult to assess in phase 3 clinical trials. “The effect of an efficacious vaccine on the course of the SARS-CoV-2 pandemic is complex and there are many potential scenarios after deployment (our edits and formatting): 1. “The ability of a vaccine to protect against severe disease and mortality is the most important efficacy endpoint, as hospital and critical-care admissions place the greatest burden on health-care systems. 2. “However, the beneficial effects of such a vaccine on a population can be observed only if the vaccine is efficacious in older adults (eg, approximately >60 years) and widespread distribution of the vaccine exists, including to people who are most susceptible to COVID-19. 3. “High coverage among these groups who are at high risk of severe COVID-19 would have the greatest effect against disease endpoints. Alternatively, vaccines that do not affect the clinical course, but reduce the transmissibility of SARS-CoV-2, could still be valuable interventions on a population level.” The Lancet article includes this diagram that succinctly describes the various potential endpoints of an efficacious COVID-19 vaccine. The article contains a detailed discussion of vaccine trial design which we recommend. Conclusion “It is probable that there will not be a single vaccine winner; diverse platforms and technologies can offer different strengths and be relevant in distinct epidemiological contexts. “Additionally, there will probably be insufficient supply, at least initially, of a single vaccine. However, collaboration and standardised approaches for assessing different efficacy endpoints will be important to allow meaningful comparison and ensure that the most effective candidates are deployed. “Following deployment, well supported pharmacovigilance studies should be established to ensure the ongoing evaluation of vaccine safety.” Vaccine Distribution Brazil approves import of China’s Sinovac vaccine Bloomberg reports that Brazil’s health regulator has authorised the importation of six million doses of the Chinese Sinvoac vaccine for Phase 3 trials, the Brazilian Health Surveillance Agency, or Anvisa, said in a statement Friday afternoon. Several other vaccine manufacturers are conducting Phase 3 trials in Brazil including Oxford / AstraZenca, Johnson & Johnson / Janssen and Pfizer. German Health Minister expects a COVID vaccine will be available early 2021 “German Federal Health Minister Jens Spahn expects a vaccine against COVID-19 for the German population ‘at the beginning of next year’. It could be January, maybe February or March, or even later.”’Of course, it would be best if a vaccine would prevent new infections. But it would also be a gain if it made the course of the disease milder,’ Spahn told Spiegel.” Lancet article reviews UK vaccine planning The UK set up its Vaccine Taskforce under the Department for Business, Energy and Industrial Strategy in May 2020; the chair Kate Bingham**, who authored the Lancet article (27 October). “The Vaccine Taskforce aims to ensure that the UK population has access to vaccines as soon as possible, while working with partners to support equitable access for populations worldwide, whether rich or poor.” Ms Bingham notes that we may never have a vaccine, and that if and when we do, the first generation of vaccines may be imperfect and “we should be prepared that they might not prevent infection but rather reduce symptoms, and, even then, might not work for everyone or for long.” The Taskforce has focused on building a “diverse” portfolio of vaccines across the various technology platforms “recognising that many, and possibly all, of these vaccines could fail.” “The Vaccine Taskforce has now secured access to six vaccines (from more than 240 vaccines in development) across four different formats: adenoviral vectors, mRNA, adjuvanted proteins, and whole inactivated viral vaccines, which are promising in different ways.” International SOS Comment Ms Bingham gives no clinical or technical evidence evidence to support her statement that “the first vaccines may be imperfect”. Rather this is a warning not to be over optimistic. **Kate Bingham is a Managing Partner at SV Health Investors. Outbreaks and Epidemiology / Melbourne begins easing lockdown Melbourne (and the state of Victoria) has recorded no new COVID-19 cases for the first time since Melbourne went into lockdown on 7 July, 111 days ago. This is the longest city lockdown since the pandemic began. From 11.59pm on Tuesday 27 October, there will be no restriction on Melbournians leaving their houses. Restaurants, hotels, cafes and bars will be able to open with up to 50 patrons outdoors and 20 indoors. The mask policy remains and working from home, where possible, remains in force. Immune Response / Oxford vaccine prompts immune response in elderly AlJazeera reports an AstraZeneca spokesperson saying that the Oxford/AstraZeneca COVID-19 vaccine produces an immune response in both younger and older adults. The vaccine also triggers lower adverse responses among the elderly. International SOS had reported on 12 September 2020 that the Moderna vaccine produced a strong immune response in older patients. International SOS Comment It is encouraging to see that both AstraZeneca and Moderna vaccines produce a good immune response in the elderly, an at risk group. Of course, we await the results of the Phase 3 trials to demonstrate these vaccines’ efficacy in preventing illness. Two studies show long-term COVID-19 immune response Two new studies demonstrate how severity of disease is predictive of longer-lasting antibody production and detail how immunity wanes over time but may exist for up to seven months.A UK study reported in Nature Microbiology examined 65 people with PCR positive COVID-19 people and 31 seropositive healthcare workers. More than 95% of patients showed SARS-CoV-2 antibodies eight days after symptom onset, but the magnitude of the neutralising antibody response appears to depend on disease severity, with lower peak antibody levels in individuals exhibiting milder disease. A Portuguese study reported in the European Journal of Immunology examined antibody levels in more than 500 hospitalised patients, healthcare workers, and volunteers who had recovered from COVID-19. The researchers found that 90% of SARS-CoV-2–positive individuals had detectable antibodies from 40 days up to seven months post-infection, with higher levels in patients with more severe disease. Pre-print showing waning antibodies & responses from two scientists A study published by Imperial College on 27 October 2020 has shown that the antibody response to the virus that causes COVID-19 wanes over time. Analysis of finger-prick tests carried out at home between 20 June and 28 September found that the number of people testing positive dropped by 26.5% across the study period, from almost 6% to 4.4%. The study abstract includes this statement; “We also show that titers are stable for at least a period approximating three months, and 36 that anti-spike binding titers significantly correlate with neutralisation of authentic SARS-CoV-2. 37. “Our data suggests that more than 90% of seroconverters make detectible neutralising antibody 38 responses and that these titers are stable for at least the near-term future.” However, Reuters reports that in a press conference, Dr Wendy Barclay** said; “We can see the antibodies and we can see them declining and we know that antibodies on their own are quite protective.“On the balance of evidence I would say, with what we know for other coronaviruses, it would look as if immunity declines away at the same rate as antibodies decline away, and that this is an indication of waning immunity at the population level.” ** Dr Wendy Barclay is the Head of the Department of Infectious Disease and Chair in Influenza Virology at Imperial College London. She leads a team of scientists studying the influenza virus and its physiology and morphology to discover novel vaccines. Response from two scientists Two renowned scientists, Dr Angela Rasmussen and Dr Florian Krammer have provided short “Tweetorials” discussing immunity and disputing the assumption that decaying antibody levels indicate decaying immunity which you can review in the full article via the link below. Two thirds of US teens fail to get needed vaccines IDSociety reports that, excluding influenza vaccine, “only 30.6% of US 17-year-olds had received all vaccines” recommended by the CDC. “The Advisory Committee on Immunisation Practices (APIP) recommends that by age 17, adolescents complete three key immunisations: human papillomavirus (HPV); quadrivalent meningococcal conjugate (MenACWY); and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap).” “State-level variations that ranged from a low of 11.3% in Idaho to a high of 56.4% in Rhode Island”. 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