Immunization PDF

Immunization Prepared by Dr Ayat Mostafa  Immuno-prophylaxis Protection against diseases may be acquired actively or passively. I) Active Immunity: exposure to infective agent → production of Abs or sensitized T cells. Immunity develops slowly but it lasts for a long time (due to memory). It m...

Immunization Prepared by Dr Ayat Mostafa  Immuno-prophylaxis Protection against diseases may be acquired actively or passively. I) Active Immunity: exposure to infective agent → production of Abs or sensitized T cells. Immunity develops slowly but it lasts for a long time (due to memory). It may be: a-Natural active immunity: following infections (clinical or subclinical). b-Artificial active immunity: after vaccination. II)Passive Immunity: -Ready made antibodies are transferred. It gives rapid protection but immunity is short lasting. -There are 2 types: a-Natural passive immunity: from mother to fetus through placenta (IgG) or in colostrum (IgA). b-Artificial passive immunity: in prophylaxis or treatment of several diseases, ex: - antitoxin serum : in ttt. of diphtheria & tetanus. - prophylactic Igs : to infants exposed to measles.  N.B. Passive active immunity: giving Igs + vaccine at the same time but at different sites of the body (ex. After needle prick with HBV +ve blood) Types of Vaccines: 1) Killed or inactivated vaccines: ex. * SinovacCOVID-19 Vaccine * TAB vaccine for typhoid and paratyphoid. * Salk vaccine for polio virus. * Human rabies vaccines. 2) Living attenuated vaccines: ex. - BCG vaccine for TB. - Sabin vaccine for polio. - MMR for measles, mumps and rubella. - 17D vaccine for yellow fever. - Rabies vaccine for animals. 3)Toxoids: by detoxifying the toxins of some bacteria (remains immunogenic, loses its toxicity) ex. Toxoid vaccines for diphtheria & tetanus. 4)Bacterial or viral components: - Capsular polysaccharide of meningococci, pneumococci & H. influenzae type b. (+ carrier protein, diphtheria toxoid). - Influenza virus vaccine; (H.A. & Neuraminidase) The hemagglutinin (HA) surface protein is the primary immune target for most influenza vaccines. The neuraminidase (NA) surface protein is often a secondary target for vaccine designs. - B. pertussis vaccine (purified protein). 5-Recombinant Ag vaccines: Ag are prepared by cloning of the coding genes after their recombination with cloning vector into E. coli or yeast. Ex. HBV, HSV, foot & mouth virus vaccines. 6-Recombinant avirulent vectors: The genes coding for the Ag of interest is inserted into the genome of an avirulent vector such as vaccinia virus. Ex. HBV vaccines Oxford/Astrazeneca vaccine Johnson & Johnson’s Janssen COVID-19 Vaccine Sputnik V vaccine All are adenovirus vector vaccine 7-Synthetic peptides vaccines: Synthetic peptide similar in its amino acid sequence to the protective antigen of the microbe. Ex. influenza virus 8-Attenuated non-reverting mutant: using genetic engineering techniques, viruses can be irreversibly attenuated by selectively deleting virulence genes. 9-DNA vaccines: plasmid vector, carrying microbial DNA encoding immunizing Ag is injected directly I.M. to the recipient. Advantages & Disadvantages of Killed and Living Attenuated Vaccines: A) Killed vaccines: Disadv. - Do not stimulate T cells (no replication I.C.) - Do not stimulate local immunity. - Incomplete protection due to destruction of some antigens during killing Adv. - short lasting, needs boosting - They are safe → given to pregnant & immuno-compromised persons.--- →Not revert to virulence - They are heat stable.→ Not need cool storage - Easy to produce B) Living attenuated vaccines: Adv. - Stimulate both humoral & cell mediated immune (CMI), both local and systemic. - Long lasting immunity, doesn’t need boosting. - Can be excreted by the immunized persons → immunize others (Herd immunity) when a large part of the population of an area is immune to a specific disease.. - They are heat labile & need proper refrigeration to remain effective. Disadv. - They may revert to virulence, may cause diseases in immunocompromised. - Expensive, difficult to prepare - May cause fever and allergic reactions to vaccine components as egg proteins in MMR COVID-19 Vaccines  In late 2019, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported to have emerged in China resulting in unprecedented public health crisis. SARS-CoV-2 is the seventh identified coronavirus and thought to be spilled over from bats into humans through an unknown intermediate +ve ssRNA, Enveloped (E) with clup-shaped glycoprotein surface spikes (S) which gives the virus its crown The corona virus (CoV) family is subdivided into 4 subfamilies: α, β (as MERS-CoV, SARS-CoV-1 & SARS-CoV- 2 which cause COVID-19), γ & δ.  Pathogenesis of SARS-CoV-2 starts after recognition and binding to host cell receptors through S1 domain, followed by cell membrane fusion mediated by S2 domain. Sites of receptor binding domains (RBDs) are different in CoVs, where SARS-CoV and SARS-CoV-2 bind to angiotensin-converting enzyme 2 (ACE2) receptors. Cryo-electron microscopy revealed that SARS-CoV-2 receptor binding is 10- to 20- fold higher than that of SARS-CoV. Unfortunately, ACE2 receptors are widely distributed in human cells surface in lungs, heart, kidney and liver. This reveals why patients may suffer from not only acute respiratory distress syndrome, but also acute myocardial and kidney injury, shock and death because of multiple organ dysfunction. Immune system has the main role in the cure of COVID-19, however, over activation of the immune system against SARS-CoV-2 results in severe cytokine storm due to release of huge numbers of inflammatory factors such as IL-2, IL-6, IL-7, GSCF, IP10, MCP1, MIP1A, and TNFα (37, 38). This virus- induced cytokine storm may be a reason for organ dysfunction and damage. Clinical Characterization SARS-CoV-2 is associated with human-to-human transmission and is thought to spread by sneezing and coughs as respiratory droplets and by direct fomite transmission. Otherwise, isolation of SARS-CoV-2 from blood and fecal swabs refer to multiple transmission routes. clinical spectrum of COVID-19 varies from asymptomatic to multi-organ manifestations. The symptoms of mild disease include fever, cough, fatigue, dyspnea, headache and sore throat but in severe case, the disease get worse in 5-10 days after onset of infection. The incubation period for symptomatic mild patients, the time from exposure to symptom onset, is 4–5 days on average. Some patients may have gastrointestinal symptoms such as vomiting and diarrhea. However in severe cases, individuals with COVID-19 develop signs and symptoms of acute respiratory distress syndrome ARDS, which require mechanical ventilation -Leucopenia, Lymphopenia, increase in D-dimer levels, chest CT shows ground- glass opacity and bilateral patchy shadows Natural infection-induced immunity to COVID-19 Idea and Types of COVID-19 vaccines Efficacy 95% 94.1% 63.09-92% 92% 93.1% 51% 79% ? 89.7% Viral vector COVID-19 vaccine Efficacy 63.09-92% 92% 93.1%  Oxford-Astrazeneca ▪ ChAdox1 ncov-19 vaccine ▪ Begun in march 2020 ▪ Doses: two doses I.M ▪ After more than three billion doses, the Oxford-AstraZeneca Covid vaccine is being withdrawn(In May 2024). can cause a rare but deadly blood-clotting condition  Disadvantages of a viral vector vaccine Just as human bodies develop immune responses to most real viral infections, our bodies also develop immunity to adenoviral vectors. That makes booster shots of adenoviral vector vaccines problematic. Upon a second injection, our bodies will release an antibody attack on the vaccine itself. And since adenoviral vectors are based on natural viruses that some of us might already have been exposed to, the vaccines might not work for everyone.  Why monkey adenovirus not human adenovirus? Not replicate in human. Why different adenovirus vectors in the second dose ? Two vector vaccine rAd26 and rAd5 (adenovirus) that lack genes for their own reproduction. These 2 vectors are used to carry and transport the gene code for the Spike protein (S) of SARS-CoV-2. First vaccination with Ad26 →the virus enter into the cells with the gene coding for the S protein → the body synthesize the S protein → immune response will be induced against it. Second vaccination with Ad5 (which is unknown to the body) → will give long lasting immunity.  RNA based COVID-19 vaccine Started at July 27,2020. Effective in 95% of trial person. Dose: two injections 21 days apart. Disadv: Storage at -80 c  SARS Cov2 variants Variants of Interest: Variants with characteristics that have been associated with changes to receptor binding, reduced immunity from previous infection or vaccination, decreased efficacy of treatments, potential diagnostic impact, or predicted increase in transmissibility or disease severity. Alpha, Beta, Gamma Variants of Concern Variants for which there is evidence of an increase in transmissibility, more severe disease, significant reduction in immunity from previous infection or vaccination, reduced effectiveness of treatments or vaccines, or diagnostic detection failures. Delta and Omicron Even after you got the vaccine…. COVID-19 protective measures Protect yourself & others Keep your distance Wash your hands frequently Cough & sneeze into your elbow Ventilate or open windows Wear a mask Doing it all protects us all. Thank you!