Chapter 17.3: Vaccination (PDF)

Vaccination 17.3-1 SARS-COV-2 1:8 11:15 https://ourworldindata.org/covid-vaccinations (Updated daily) https://covid19.who.int (updated weekly) Global Situation Total cases 13.57 billion doses have been admini...

Vaccination 17.3-1 SARS-COV-2 1:8 11:15 https://ourworldindata.org/covid-vaccinations (Updated daily) https://covid19.who.int (updated weekly) Global Situation Total cases 13.57 billion doses have been administered globally 70.6% of the world population has received at least one does (32.7% in low income countries ) Global Situation Total deaths Edward Jenner and Smallpox – the foundation of immunology An “old world” disease of unknown origin – 20 to 60% fatality Known from early on that people who survived would not get the disease again By the 1700’s it was noticed that “milkmaids” who had caught cowpox did not get smallpox In May 1796 Jenner took material from the pustule of a milkmaid and injected it into an 8 year old boy who had never been exposed to cowpox or smallpox In July 1796 he injected the boy with live smallpox and no disease developed Jenner's work represented the first scientific attempt to control an infectious disease by the deliberate use of vaccination Latin word for cow is vacca and cowpox is vaccinia = vaccination 17.3-2 How effective is vaccination: smallpox Smallpox officially eradicated after a three year period where no cases were reported The only human disease eradicated by vaccination Smallpox vaccines are no longer administered But it’s not really “gone”: there are frozen samples in the US and Russia and controversy over whether or not they should be destroyed “In September 2019, the Russian lab housing smallpox samples experienced a gas explosion that injured one worker. It did not occur near the virus storage area, and no samples were compromised, but the incident prompted a review of risks to containment” “As of May 2021, based on the latest meeting of the WHO Advisory Committee on Variola Virus Research “Member States noted the report (from 2019), emphasized that the benefits of the variola virus research programme overseen by WHO should be accessible to all and the decision on the date of destruction of live variola virus stocks should be deferred by up to five years to afford time to reflect on the best options for global public health” There are measures in place to prevent people from re-creating smallpox. The World Health Organization recommends that no institution should be allowed to possess more than 20 percent of the smallpox genome and companies that synthesize DNA for research purposes are required to check the orders they receive against certain human pathogens, 17.3-3 How effective is vaccination: measles Measles: a highly contagious viral infection that can lead to pneumonia, encephalitis (brain inflammation), pregnancy complications One of the leading vaccine preventable causes of death world-wide In healthy children 1 out of every 1000 with measles progress to acute encephalitis often resulting in permanent brain damage In healthy children 1 to 2 out of every 1000 will die from respiratory and neurological complications In immunocompromised individuals death rate is close to 30% Measles is still a global issue In the US Around the world 17.3-4  How effective is vaccination: polio Poliomylitis: a viral infection causing nerve injury leading to partial or full paralysis Today, there are only two countries left that are still polio- endemic: Pakistan, Afghanistan, and Nigeria. Polio vaccines are still given because it has not been eradicated and international travel is so high vaccination is needed to prevent epidemic occurance 17.3-5 Note: polio virus detected in NY state wastewater in April 2022 Herd Immunity Herd immunity: when the majority of a population is immune to a pathogen, the chances of a susceptible individual contacting an infected individual is low 17.3-6 Infectious diseases remain the leading cause 17.3-7 of death world wide FYI only: Features of Pathogens that Impact Vaccine Effectiveness Most effective against pathogens that Do not undergo much antigenic variation Do not establish latency Do not interfere with the host immune response Do not have animal reservoirs Measles vaccine currently 17.3-8 used is heat sensitive Why use passive immunity? Deficiency in antibody synthesis (congenital or acquired) Insufficient time to wait to mount an active adaptive immune response before complications (possibly fatal) occur 17.3-9  Live attenuated vaccines are the most common (also includes nasal influenza) FYI slide Novavax vaccine for Covid-19 Johnson and Johnson vaccine for Covid-19 (no longer in use Pfizer and Moderna vaccines for Covid-19 https://www.vaccines.gov/basics/types 17.3-10 Most viral vaccines are made from killed or attenuated viruses In an “attenuated” virus the virus is still alive but has lost its pathogenicity in humans by being passed through a non-human cell line where it does not grow well until it loses its pathogenicity and still grows in human cells but not well When injected as a vaccine provokes an immune response but not the disease Often confer lifetime resistance New molecular techniques available now to make attenuated viruses 17.3-11 Most viral vaccines are made from killed (inactivated) or attenuated viruses Killed viruses , unlike attenuated viruses, cannot reproduce All nucleic acids must be inactivated Immune response is often not as potent as attenuated vaccine (boosters often required) 17.3-12 Most flu vaccines (~82%) are produced by growing flu viruses in eggs This process has been used for over 70 years to make both: Innactivated (killed) for the flu shot Attenuated for the nasal spray flu vaccine There is now a cell-based flu vaccine grown in cultured mammalian cells Not dependent on the supply of eggs Also a recombinant vaccine using HA (only one approved at this time) CNN: Sun March 29, 2020 The US keeps millions of chickens in secret farms to make flu vaccines Few people know where the chickens are kept -- their locations are undisclosed as a matter of national security. 17.3-13 SARS-COV2 does not replicate inside of eggs What’s in the current flu shot (for the Northern Hemisphere) What’s in a flu shot? Currently: primarily inactivated (killed) virus vaccines are used, but there are at least 10 manufacturers of influenza vaccine and in addition to inactived (killed) whole virus, split and subunit vaccines are used as well as attenuated Because of drift and shift, flu vaccine has to be reformulated every year to reflect the viruses currently circulating in the human population in each hemisphere The vaccine will contain the viruses circulating in late spring because these are generally the viruses that will cause epidemics the following winter What a flu shot does is generate an antibody response FYI slide The 2019/20 seasonal influenza vaccine Contained the following strains: A/Brisbane/02/2018 (H1N1) 2021/22 vaccine contained: A/Kansas/14/2017 (H3N2) A/Wisconsin/588/2019 (H1N1) B/Colorado/06/2017 A/Cambodia/e0826360/2020 (H3N2) B/Phuket/3073/2013-like B/Washington/02/2019- like virus (B/Victoria lineage) B/Phuket/3073/2013-like virus (B/Yamagata lineage) 2023-2924 A/Wisconsin/67/2022 (H1N1) A/Darwin/6/2021(H3N2) B/Austria/1359417/2021-like virus (B/Victoria lineage); 17.3-14 B/Phuket/3073/2013-like virus (B/Yamagata lineage) How long does it take to make a vaccine Creation of a rotovirus vaccine took 30 years of research and development Rotovirus causes severe (childhood) diarrhea 600,000 deaths world-wide Discovered in 1973 Rotarix: an attenuated human retrovirus RotaTeq: mixture of 5 cattle rotoviruses that are nonpathogenic to humans FYI slide 17.3-15 How long does it take to make a vaccine FYI slide Time course of the H1N1 pandemic of 2009 and development of a vaccine against it 17.3-16 What happens when people stop taking vaccines As few children were vaccinated against measles virus the incidence of infections increased 17.3-17 There is no scientific link between autism and vaccination In 1998 the Lancet published a report by Andrew Wakefield and collegues that suggested the MMR vaccine may predispose to autism but in actuality the data was fraudulent and there was no connection Wakefield’s research had been funded by lawyers representing parents who were suing vaccine-producing companies and was based on selective sampling of only 12 children using questionable methodology He was shown to have participated in deliberate fraud by picking and choosing data that suited his case and fabricating other data Many large epidemiological studies have found no difference in risk of developmental delays between children who receive the MMR vaccine and those who don’t Where is Wakefied now? In the States, hailed as a celebrity by the anti- vaxxer movement and many “prominent” figures, supported very, very generously by them and ….. “The Doctor who Fooled the World” by Brian Deer – published Sept 2020 17.3-18 Adjuvants are added to vaccines to activate and enhance the response to antigen Adjuvents activate the innate immune response which is required to generate an adaptive immune response Alum, the first adjuvant is not very powerful Strategy of newer adjuvants is recognition by Toll-like receptors 17.3-19 Viruses FYI slide Particle consisting of nucleic acid (RNA or DNA) enclosed in a protein coat and capable of replicating within a host cell and spreading from cell to cell All viral genomes encode three types of proteins: for replication for packaging and delivery for modification of host cell There are ~ 270 virus species (as of 2022) that are known to be able to infect humans The first of these to be discovered was yellow fever virus in 1901 three to four new species are still being found every year 17.3-20 Coronavirus FYI slide Coronaviruses are zoonotic, https://www.cdc.gov/coronavirus/types.html meaning they are transmitted Coronaviruses are named for the between animals and people crown-like spikes on their surface Detailed investigations found that SARS-CoV was transmitted Human coronaviruses were first from civet cats to humans and identified in the mid-1960s MERS-CoV from dromedary camels to humans The seven coronaviruses that can Several known coronaviruses infect people are: are circulating in animals that Common human coronaviruses that have not yet infected humans cause 20% of “common colds 1.229E 2.NL63 3.OC43 4.HKU1 5.SARS-CoV – identified in 2003 (causes severe acute respiratory syndrome, or SARS) 6.MERS-CoV – identified in 2012 (causes Middle East Respiratory Syndrome (MERs) 7.SARS-CoV-2 – identified in 2019 (causes COVID-19) 17.3-21  Vaccines have yet to be made against pathogens that establish chronic infections Most effective vaccines target acute infections 17.3-22 Tuberculosis is included because the vaccine is not very effective Measles is included because the current vaccine needs to be kept refrigerated Immune system response to a new (viral) antigen FYI slide First defense against a viral attack: Complement proteins and macrophages (should be able to take care of small infections) If this isn’t enough: Natural killer cells (activated) Additional phagocytes (neutrophils and more macrophages) Signals that this still is not enough are: production of interferon and host cells killed by virus infection Remember: adaptive immune system is slow to react particularly against a virus it has never seen before (and in the case of a viral infection generally only comes into play only when the innate immune system is overwhelmed) 17.3-23 Respiratory viruses bind to a “normal” membrane protein and trigger endocytosis 17.3-24 Viruses replicate and leave the cell via membrane budding, killing the cell in the process and going on to infect new cells FYI slide 17.3-25 FYI slide 17.3-26 What are RNA vaccines and mRNA was discovered in the how do they work? early 60’s Delivery into cells was developed in the 70’s In the following decades technical challenges were overcome and a method of safe delivery into cells was developed The first mRNA vaccine was developed against the Ebola virus but had no commercial potential mRNA technology was being used for other applications though including cancer therapeutics The commercial potential arrived with SARS-CoV-2 This is NOT a new technology and has an enormous potential for other viruses and pathologies 17.3-27 How do mRNA vaccines work Goal is to: produce neutralizing antibodies that recognize the spike protein generate CD8+ cytotoxic T-cells 17.3-28 What are RNA vaccines and how do they work? 17.3-29 How does the Novovax protein subunit vaccine work? 17.3-30 Three Covid vaccines currently in use in Canada and US Pfizer-BioNTech and Moderna Vaccines are both RNA vaccines Novavax vaccine is a protein subunit vaccine Vaccines that require two doses are not uncommon: Measles-mumps-rubella (MMR) Hepatitis A and Hepatitis B Shingles vaccine Goal is to: produce neutralizing antibodies that recognize the spike protein generate CD8+ cytotoxic T-cells How long will the neutralizing antibodies remain in circulation? How long will the CD8+ T-cells be active? Will memory cells be produced and how effective will they be? The Moderna vaccine works on the same principles as the Pfizer vaccine The lipid nanoparticle delivery system is a bit different Why booster shots? Clinical trials demonstrated a relatively weak immune response with one dose and a stronger immune response with a second dose 17.3-31 Learning Objectives: Understand what Herd Immunity is Understand the difference between active immunity and passive immunity Understand what is meant by attenuated vaccines Understand what is meant by inactivated (killed ) vaccines Be clear on what mRNA vaccines are, how they are developed and how they get into cells Understand what a subunit vaccine is Understand what an adjuvant is and why it is used 17.3-32