As the days unfold with a seeming sameness in this odd summer of the pandemic, news of vaccine clinical trials begins to trickle in, and another buzzword from epidemiology is entering the everyday lexicon: durability.
To be successful, a vaccines protection must last or booster shots periodically restore it. Some vaccines lose efficacy over time, including those for yellow fever, pertussis, and of course influenza.
For some vaccines, antibodies and the B cells that make them persist and protect for a long time. For other infectious diseases, like TB and malaria, T cells are needed in vaccines too. B and T cells (lymphocytes) are types of white blood cells, which are part of the immune system.
Give amanafishand you feedhimfor a day.Teach himhow tofishand you feedhimfor a lifetime, said Chinese philosopher Lao Tzu, founder of Taoism.
Tzu might have been referring metaphorically to the immune systems response to viral infection: an initial rush of antibodies that fades as a longer-lasting cell-based memory builds that primes the body to rapidly release antibodies upon a future encounter with the pathogen.
Antibodies are proteins, so they dont make more of themselves as cells might. Thats why antibodies collected from plasma from a person whos recovered from COVID-19 lasts a few weeks. Its also why an antibody medicine like Regenerons dual-antibody REGN-COV2 provides only short-term protection, a bridge until a vaccine becomes available.
To remain effective over a reasonable period of time, a vaccine must mimic the memory component of an immune response, which arises from B and T cells and is therefore called the cellular immune response. The shorter-term release of antibodies into the bloodstream is the humoral immune response (humor means fluid).
A strong antibody response to a vaccine may be a harbinger of lasting B and T cell protection, but vaccines may be marketed before their durability is known a complete understanding of how long a vaccines protection lasts can take years. The vaccine against the mumps, for example, went on the market in 1967, but in 2006, several colleges had outbreaks, among students whose childhood mumps vaccine had worn off. A booster extends the coverage.
Clues to a COVID-19 vaccines durability come from natural immunity from past coronavirus infections. The antibody response to SARS and MERS persisted less than a year. But so far, the cellular immune response to SARS, the older of the two, has lasted eleven years.
Clinical trials to evaluate COVID-19 vaccines in people consider both antibody production and the building of cellular immunity. And a vaccine can be even more protective than natural immunity.
A vaccine elicits memory B and T cells so the immune system remembers how to fight the disease in the future. Natural infection is not likely to produce durable immunity and vaccination will be essential to produce herd immunity to reduce the probability of viral transmission, said Arlene Sharpe MD PhD co-director of the Evergrande Center for Immunologic Diseases at Harvard Medical School and Brigham and Womens Hospital on a recent zoom that MassCPR, a group of Boston-area institutions that formed in early March in response to the pandemic, held.
The immune system isnt as easy to visualize as a skeleton splayed out in a Halloween decoration, the flattened entrails of a roadkill, or the circulatory system, which even Groucho Marx in the film Horse Feathers could easily explain. (Let us follow a corpuscle on its journey through the body.)
Instead, the immune system is an army of billions of cells and their secretions that stand ready to attack newly encountered pathogens, remember old ones, and at the same time recognize self, protecting the bodys own tissues. The cells travel in clear lymph fluid, passing through lymph nodes that filter out debris.
The immune system reacts in three stages. First, physical barriers keep pathogens out: skin, earwax, waving cilia in the throat, stomach acid, diarrhea. Next, innate immunity unleashes a bath of inflammatory molecules that are a generalized response to infection.
Finally comes adaptive immunity, which is specific and provides the memory that a vaccine emulates. In addition to T and B cells, innate immunity includes the wandering, blobby macrophages, which engulf pathogens and are festooned with bits of a pathogens surface antigens that alert other immune defenses.
Antibody production begins when a stimulated B cell divides in the bone marrow, giving rise to two types of cells. One, a plasma cell, has a clear oblong area that is a ginormous Golgi apparatus, which processes 2,000 antibodies per second that enter the circulation.
The second daughter cell of a dividing B cell is a memory B cell. Like the name suggests, a memory B cell hangs around, and if the pathogen shows up again, jumps into action and pumps out more antibodies, cutting off the new infection fast.
An important part of the antibody response is that its polyclonal differently-shaped antibodies are produced, each recognizing and binding to a different part of a pathogen, like using different weapons to tackle different parts of an enemys body.
Some antibodies just bind to a pathogen, but others neutralize it, and those are the ones that make a vaccine or immune response effective. Yet certain other antibodies actually enhance infection; vaccines are designed to block this from happening.
T cells come in several varieties and exert complex effects.
Tracking T cells is important in evaluating potential vaccine durability. And although we only have a half-year of data, the natural infection suggests that antibody responses may be short-lived or not strong enough.
Investigators are reporting the antibody response in humans infected with COVID who recover tends to drop relatively quickly. To some people thats an alarm bell and they guess that a vaccine will show little durability. But following recovery from an acute infection, a decline in antibodies is normal B cell biology and is exactly what we predict, said Daniel Barouch, MD, PhD, professor of medicine, Harvard Medical School and director, Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center.
One of the first reports showed antibodies decreasing by half in just 37 days among a small sample of people who had mild cases. Thats similar to SARS and MERS, in which antibodies fade away within a year. But so far, reports of phase 1 clinical trial results for two COVID vaccines are encouraging.
The first interim report, published in The New England Journal of MedicineJuly 14, found that all 45 participants who received one of three doses of Modernas mRNA-1273 vaccine made antibodies, more with the higher dose. Binding antibodies appeared by day 15 and neutralizing antibodies after a second dose on day 28. Neutralizing antibodies are a biomarker of vaccine protection for other respiratory viruses, so thats good news.
Responses are comparable to what occurs with natural infection, and perhaps a little higher. Data are encouraging; the strategy elicits immune responses that are targeted against the virus, said Lindsey R. Baden, MD, associate professor of medicine, Harvard Medical School and director of clinical research, Brigham and Womens Hospital. The study used antibodies in plasma from recovered patients as a control for the natural immune response, and the vaccine exceeded that comparison.
Even better news: participants made T cells. Helpers appear first, which pump out a specific soup of cytokines, and then after the second dose of vaccine, killers appear, making sure that any remaining viruses cant replicate.
The phase 1 trial showed that the middle of three doses is best for tempering efficacy with side effects. Phase 2 began in May and phase 3, began on July 27. Overall, depending on the number of trials that progress, hundreds of thousands of people may participate.
Modernas vaccine (mRNA-1273) is designed to enhance visibility to the immune system. The target cell translates it into an engineered version of the viruss spike protein that tames the inflammatory response. The spike is also tweaked to be more stable than the natural one.
On July 20 the second clinical trial report came from the Oxford COVID Vaccine Trial Groups candidate ChAdOx1, in The Lancet. That vaccine consists of the genetic instructions for the spike protein delivered in a chimpanzee virus.
Like the mRNA vaccine, Oxfords candidate is given in doses 28 days apart. And it, too, evokes both a humoral (antibody) and cellular (T cell) response.
So far, the numbers of vaccinated people are small, but the reports are optimistic.
With clever variationson the clinical trial theme, like overlapping phases and designing spike proteins to be more visible to the immune system, it may indeed be possible to barrel through phase 3 clinical trials that test a statistically significant number of people. But post-marketing surveillance, a normal part of drug development, is going to be critical.
The participants in the MassCPR zoom marveled that vaccine development for COVID-19 is so far taking 5 to 10 months, compared to the historical 5 to 10 years.
We are only months into knowing about this virus, so any longevity of the immune response we have to interpret with care because our understanding of the biology and durability of the biology will take time. The virus will evolve and we have to take that into consideration, said Baden. He showed data from monkeys that suggest a long-lasting effect is possible.
Practically speaking, the phase 3 trials will take time because the participants arent being injected with virus, for ethical reasons. Instead, investigators must wait for the volunteers to encounter the virus in their communities, to see if a smaller percentage of vaccinated people become infected than the unvaccinated control groups. And thats why a vaccine by the end of the year would be quite a surprise for many of us, said Ken Mayer, MD, of the Fenway Institute.
Well have increasing clarity as the next 3 to 6 months proceed with a suite of clinical trials underway or soon to be. Most optimistic is late fall for first availability for an Emergency Use Authorization. But a tremendous number of things would have to go perfectly to achieve that. Early 2021 is more realistic, said Barouch. An EUA brought COVID-19 treatment remdesivir to patients before the official FDA approval.
Baden agreed that early 2021 is more feasible. He points out the potential savings of 6 to 12 months from beginning to manufacture candidate vaccines before their clinical trials conclude, well before. Financial risks are acceptable, safety not, and thats why it will take at least 3 to 6 months more.
Once a vaccine is out there, attention will turn to epidemiology. What percentage of the population must be vaccinated or have natural immunity to induce herd immunity? And how many people will actually take a vaccine?
If several vaccines make it to the finish line, how will people be assigned to them? People over age 65, for example, would benefit most from a vaccine that includes an adjuvant, which is a chemical that affects the immune response. A vaccine candidate from Australian biotech company Vaxine Pty Limited, for example, includes a complex sugar that lowers the risk of the vaccine triggering an excessive immune response. The sugar adjuvant has worked well in vaccines against influenza, hepatitis B, and West Nile virus, according to Nikolai Petrovsky, PhD, research director at the company.
Assessing the all-important T cell response will take time, too, because thats the way the cellular immune response unfurls in nature. Gradually. A full immune response is a finely-tuned process that is a consequence of millennia of evolution not of politics, PR, potential profits, or wishful thinking.
Ricki Lewis has a PhD in genetics and is a genetics counselor, science writer and author of Human Genetics: The Basics. Follow her at her website or Twitter @rickilewis.
- Atsena Therapeutics Raises $55 Million Series A Financing to Advance LCA1 Gene Therapy Clinical Program, Two Preclinical Assets, and Novel Capsid... - December 17th, 2020
- Locanabio Announces $100 Million Series B Financing to Advance Portfolio of Novel RNA-Targeted Gene Therapies for Neurodegenerative, Neuromuscular and... - December 17th, 2020
- NeuBase Therapeutics Announces Positive Preclinical In Vivo Data for PATrOL-enabled Anti-gene for the Treatment of Myotonic Dystrophy Type 1 -... - December 17th, 2020
- Genetic Analysis Services Market: Uptake of Next-generation Sequencing and Multi-gene Tests to Drive Market - BioSpace - December 17th, 2020
- FDA Clears Genetic Modification in Pigs for Biomedicine and Food - The Scientist - December 17th, 2020
- Key Genes Related to Severe COVID-19 Infection Identified - The Scientist - December 17th, 2020
- UNLV Researcher on the Curious Case of COVID-19 Reinfection - UNLV NewsCenter - December 17th, 2020
- Genomics and medicine it's complicated | Health | willistonherald.com - Williston Daily Herald - December 17th, 2020
- Emedgene collaborates with Illumina to scale the interpretation of genomic data for rare diseases - PRNewswire - December 17th, 2020
- Polymerase Chain Reaction Market | Increased Outbreak of Infectious Diseases to Accentuate Demand in the Market - BioSpace - December 17th, 2020
- LogicBio Therapeutics names Daphne Karydas and Jeff Goater to Board of Directors - BioSpace - December 17th, 2020
- rBIO Achieves Crucial Milestone on Mission to Lower the Cost of Insulin by 30% - BioSpace - December 17th, 2020
- Report: More than 1,300 Medicines and Vaccines in Development to Help Fight Cancer - PRNewswire - December 17th, 2020
- San Diego's Locanabio raises $100 million for treatments aimed at degenerative diseases - The San Diego Union-Tribune - December 17th, 2020
- Worldwide SNP Genotyping Industry to 2025 - Pharmacogenomics Led the End-user Segment of the SNP Genotyping Market - ResearchAndMarkets.com - Business... - December 17th, 2020
- Potential Weakness in SARS-CoV-2 Discovered Single Protein Needed for COVID-19 Virus to Reproduce and Spread - SciTechDaily - December 17th, 2020
- Landing of $75M expansion of Texas-based Taysha adds to Triangle's growing gene therapy hub - WRAL Tech Wire - December 17th, 2020
- Track the Vax: What Do We Need to Know About the New Vaccines? - Everyday Health - December 17th, 2020
- Medical history from the year you were born - Quad City Times - December 5th, 2020
- Sarepta Therapeutics to Share Clinical Update for SRP-5051, its Investigational PPMO for the Treatment of Duchenne Muscular Dystrophy - GlobeNewswire - December 5th, 2020
- Biochip Market | Increased Popularity of Personalized Medicine to Boost the Market Growth | Technavio - Business Wire - December 5th, 2020
- December: Baby birth weight research | News and features - University of Bristol - December 5th, 2020
- Global Next Generation Sequencing Market (2020 to 2026) - Growth, Trends, Competitive Landscape, and Forecasts - GlobeNewswire - December 5th, 2020
- NIH researchers link cases of ALS and FTD to a mutation associated with Huntington's disease - National Institute on Aging - December 5th, 2020
- Precision Medicine Market Poised to Grow at 11.5% By 20227 - GlobeNewswire - December 5th, 2020
- Fact check: mRNA vaccines kept at very cold temperatures so that they do not break apart; COVID-19 vaccines will not genetically modify humans -... - December 5th, 2020
- Stoke Therapeutics Announces Presentations Related to the Company's Work to Advance STK-001, the First Potential New Medicine to Target the Underlying... - December 5th, 2020
- King George III's illness debunked as symptom 'caused by medicine prescribed to him' - Express - December 5th, 2020
- Stoke Therapeutics to Present at the Needham Virtual Epilepsy & Pain Specialty CNS Therapeutics Conference - Business Wire - December 5th, 2020
- Following the science: the writers who have made sense of Covid - The Guardian - December 5th, 2020
- Gene experts claim they identified human genes that can protect against Covid-19 - CNBC - November 23rd, 2020
- Genome Medical Reaches 90 Million Covered Lives in US - PRNewswire - November 23rd, 2020
- Sarepta Therapeutics Named One of The Boston Globe's Top Places to Work 2020 - GlobeNewswire - November 23rd, 2020
- New Study Highlights the Importance of Genetic Testing for Pancreatic Cancer Patients - PRNewswire - November 23rd, 2020
- Baylor Genetics Launches Combination Test for COVID-19 and Influenza A and B; Multi-Panel Test Seeks to Address Dilemma of "Overlapping symptoms... - November 23rd, 2020
- CHOP Researchers Reverse Severe Lymphatic Disorder in Patient with Noonan Syndrome by Targeting Genetic Pathway - BioSpace - November 23rd, 2020
- Myriad Genetics Announces Global Expansion of Myriad myChoice Tumor Testing in Europe and China - GlobeNewswire - November 23rd, 2020
- Epigenetics and pulmonary diseases in the horizon of precision medicine: a review - DocWire News - November 23rd, 2020
- Four years after landing in US, graduating ISU senior is on his way to medical school - Iowa State University News Service - November 23rd, 2020
- Lethal brain infections in mice thwarted by decoy molecule - Washington University School of Medicine in St. Louis - November 23rd, 2020
- Reducing barriers to mainstream gene therapy - BioPharma-Reporter.com - September 4th, 2020
- Mapping Genetic Diversity of Lung Tumors Over Time May Lead to More Effective Therapies - UCSF News Services - September 4th, 2020
- Multi-site study to evaluate the role of testing guidelines in ensuring access to genetic information for men with prostate cancer - PRNewswire - September 4th, 2020
- Global Prime Editing Market to Witness Heightened Growth During the Period 2020 2030 - The Daily Chronicle - September 4th, 2020
- Liquid biopsies to disrupt the oncology testing market - Medical Device Network - September 4th, 2020
- Global RNA-interference (RNAi) Market Growth, Trends and Forecasts to 2025: Focus on Key Players Alnylam Pharmaceuticals, Arrowhead, Quark... - September 4th, 2020
- Yale researchers find a cause and possible treatment for Fragile X - Yale News - September 4th, 2020
- 'Coming into their own': FDA approval of liquid biopsy tests puts early, less invasive cancer detection in broader reach - USA TODAY - September 4th, 2020
- Fusion Genes Associated With More Aggressive Papillary Thyroid Cancer in Pediatric Patients - Targeted Oncology - September 4th, 2020
- Existing Class of Drugs May Improve Neurological Function in Patients with Rare, Aggressive Genetic Disorder - Newswise - September 4th, 2020
- Genomic analysis reveals insights on virulent, emerging foodborne pathogen - UB Now: News and views for UB faculty and staff - University at Buffalo... - September 4th, 2020
- Hyperthyroidism is associated with breast cancer risk and mammographic and genetic risk predictors - 2 Minute Medicine - September 4th, 2020
- Health history platform launches to trace genetic conditions | Digital Healthcare - Healthcare Global - Healthcare News, Magazine and Website - September 4th, 2020
- New HIV Gene Therapy, CAR-T Treatments Could be on the Horizon for Patients - BioSpace - September 4th, 2020
- Cell Suicide Gene Further Linked to Immunotherapy Response - Technology Networks - September 2nd, 2020
- Genetic mutations may be linked to infertility, early menopause - Washington University School of Medicine in St. Louis - September 2nd, 2020
- How to use precision medicine to personalise COVID-19 treatment according to the patient's genes - Down To Earth Magazine - September 2nd, 2020
- UCT professors research offers hope of treatment for sickle cell anaemia - Daily Maverick - September 2nd, 2020
- Association of recent stressful life events with mental and physical health in the context of genomic and exposomic liability for schizophrenia - 2... - September 2nd, 2020
- Finding order in the chaos of cancer mutations - Drug Target Review - September 2nd, 2020
- Mustang Bio Announces Orphan Drug Designation for MB-107 for the Treatment of X-linked Severe Combined Immunodeficiency in Newly Diagnosed Infants -... - September 2nd, 2020
- Novavax Announces Publication of Phase 1 Data for COVID-19 Vaccine Candidate in The New England Journal of Medicine - GlobeNewswire - September 2nd, 2020
- Department of Genetic Medicine | Johns Hopkins Medicine - August 10th, 2020
- Genetic Medicine | Internal Medicine | Michigan Medicine ... - August 10th, 2020
- Genetic Medicine | Department of Medicine - August 10th, 2020
- Genomics and Medicine - Genome.gov - August 10th, 2020
- New Approach to Treating Osteoarthritis Advances | NYU Langone News - NYU Langone Health - August 10th, 2020
- Stoke Therapeutics Reports Second Quarter Financial Results and Provides Business Updates - Business Wire - August 10th, 2020
- Here's Why Shares of Editas Medicine and Beam Therapeutics Are Soaring Today - Motley Fool - August 10th, 2020
- Grant will fund study into COVID outcome disparities in NYC - Cornell Chronicle - August 10th, 2020
- A versatile genetic control system in mammalian cells and mice responsive to clinically licensed sodium ferulate - Science Advances - August 10th, 2020
- Spark Therapeutics Deepens Drug Development Expertise in Hematology and Rare Disease with Appointment of Gallia G. Levy, MD, Ph.D., as Chief Medical... - August 10th, 2020
- Chromosomal Rearrangements Associated with Chemotherapeutic Drug Resistance | McDonnell Boehnen Hulbert & Berghoff LLP - JD Supra - August 10th, 2020
- Jae Jung, Ph.D., Appointed as Chair of Cleveland Clinic Lerner Research Institute's Department of Cancer Biology - Health Essentials from Cleveland... - August 10th, 2020
- The UK and TCELS to jointly support COVID-19 research in Thailand - GOV.UK - August 10th, 2020
- Akouos Announces Expansion of Executive Team and Board of Directors - BioSpace - August 10th, 2020
- Medical and neurobehavioural phenotypes in male and female carriers of Xp22.31 duplications in the UK Biobank. - Physician's Weekly - August 10th, 2020
- Coronavirus vaccine breakthrough: New generation cure that stops virus developed - Express - August 10th, 2020
- Global Cell and Gene Therapy Market, Forecast to 2025 by Product, Disease, End-user and Region - COVID-19 Updated - PRNewswire - August 10th, 2020
- Not Everyone Needs 8 Hours of Sleep, New Research Reveals | Time - TIME - August 10th, 2020