Vacinação Flashcards

Question

Vacinas contra o SARS-Cov-2 - comparação!

Answer 1

Moderna (US) type: mRNA Ag: full-length spike protein with proline substitutions dose: 100 ug dosage:2 doses 28d apart storage conditions: -25 to -15ºC, 2-8ºC for 30d, room temperature < 12h efficacy against severe COVID-19: 100% 14d after second dose overall efficacy: 92.1% 14d after 1 dose, 94% 14d after second dose current approvals: EUA - US, EU, Canada, UK Pfizer-BioNTech (US) type: mRNA Ag: full-length spike protein with proline substitutions dose: 30 ug dosage: 2 doses 21d apart storage conditions: -80 to -60ºC, 2-8ºC for 5d, room temperature < 2h efficacy against severe COVID-19: 88.9% after 1 dose overall efficacy: 52% after 1 dose, 94.6% after second dose current approvals: EUA - US, EU, Canada, UK Janssen/ Johnson&Johnsons (US) type: viral vector Ag: recombinant, replication-incompetent human adenovirus serotype 26 vector encoding a full-length, stabilized SARS-Cov-2 S protein dose: 5*10^10 viral particles dosage: 1 dose storage conditions: -20ºC, 2-8ºC for 3 mo efficacy against severe COVID-19: 85% after 28d, 100% after 49d overall efficacy: 72% in the US, 66% in latin america (at 28d) current approvals: EUA - US, EU, Canada AstraZeneca/Oxford (UK) type: viral vector Ag: replication-deficient chimpanzee adenoviral vector with the SARS-Cov-2 S protein dose:5*10^10 viral particles dosage: 2 doses 28d apart storage conditions: 2-8ºC for 6mo efficacy against severe COVID-19: 100% 21d after first dose overall efficacy: 64.1% after 1 dose, 70.4% 14d after second dose current approvals: EUA - WHO/Covax, the UK, India, and Mexico +outras... Novavax (US) - protein subunit ... EUA application planned CureVac/GSK (DE) - mRNA - ... Sputnik V (RU) - viral vector -... EUA - Russia, Belarus, Argentina, Serbia, UAE, Algeria, Palestine, and Egypt Sinovac (CH) - inactivated virus - ... EUA - China, Brazil, Columbia, Bolivia, Brazil, Chile, Uruguay, Turkey, Indonesia, Azerbaijan Sinopharm (CH) - inactivated virus - ... EUA - China, UAE, Bahrain, Serbia, Peru, Zimbabwe (EUA - emergency use application)

Answer 2

The two vaccine formulations —mRNA encoding the SARS-CoV-2 spike (S) protein encapsulated in lipid nanoparticles or adenovirus (AdV) vectors encoding the S protein — gain entry into dendritic cells (DCs) at the injection site or within lymph nodes, resulting in production of high levels of S protein. In addition, innate sensors are triggered by the intrinsic adjuvant activity of the vaccines, resulting in production of type I interferon and multiple pro-inflammatory cytokines and chemokines. RNA sensors such as Toll-like receptor 7 (TLR7) and MDA5 are triggered by the mRNA vaccines, and TLR9 is the major double-stranded DNA sensor for the AdV vaccine. The resultant activated DCs present antigen and co-stimulatory molecules to S protein-specific naive T cells, which become activated and differentiated into effector cells to form cytotoxic T lymphocytes or helper T cells. T follicular helper (TFH) cells help S protein-specific B cells to differentiate into antibodysecreting plasma cells and promote the production of high affinity anti-S protein antibodies. Following vaccination, S protein-specific memory T cells and B cells develop and circulate along with high affinity SARS-CoV-2 antibodies, which together help prevent subsequent infection with SARS-CoV-2.

Answer 3

• Vaccination is a powerful strategy for preventing infections. The most effective vaccines are those that stimulate the production of high-affinity antibodies and memory cells. Many approaches for vaccination are in clinical use and being tried for various infections. • The development of a new vaccine requires much basic science research, huge investments of time and money in development (with more failures than successes), and a clear prior delineation of the specific immune targets of a vaccination program, called correlates of immune protection. • Passive immunity, which is only temporary and does not engage the host’s immune response or generate memory, can be acquired naturally (e.g., in utero transplacental IgG) or delivered artificially to protect individuals from subsequent infectious disease or recent venom exposures, and in those who lack humoral responses. • Active immunity can be triggered by either natural infection or artificial exposure to some form of a pathogen, such as a vaccine, with a goal of inducing a memory response that will be protective in the future. • The introduction of vaccine campaigns, especially in children, has vastly reduced the risk of death from infectious disease worldwide. • Herd immunity occurs when a large portion of a community (the herd) becomes immune to a disease, making the spread of disease from person to person unlikely. As a result, the whole community becomes protected — not just those who are immune. The more contagious a disease is, the greater the proportion of the population that needs to be immune to the disease to stop its spread. • Live attenuated vaccines are weakened forms of the infectious agent used to trigger a robust adaptive immune response. Advantages include effector cell types well matched with natural infection (including CTLs) and strong, long-lived, protective memory after even a single exposure. An important disadvantage is the potential for reversion to more virulent forms that can cause disease. • An infectious organism can be killed or chemically inactivated, and then administered as a means to trigger protective adaptive immune responses. Advantages include the low risk of reversion and disease, plus rapid production times. Disadvantages include lower immunogenicity, poor cellmediated immune responses (especially CTLs), and a weaker protection that can necessitate booster shots. • Subunit vaccines use just a part of an inactivated or killed infectious agent; thus they share many of the same advantages and disadvantages, with the added advantage of simpler, safer, and more rapid production time. • When subunit antigens are poor immune stimulators they can be combined with strong immune activators, either as a fused protein (conjugate) or in a mixture of proteins (multivalent), allowing the strong immunogen to act as a carrier for the weaker antigen, inducing a more robust immune response against both. • Adjuvants are additives that can be mixed in with a vaccine to stimulate innate signals that help to instruct and enhance the adaptive response, and are modelled on natural PAMPs known to help direct specific adaptive pathways. • Viruses and other microbes that replicate inside cells but cause no disease can be used as live delivery vehicles for fragments of pathogens. These recombinant vector vaccines retain many of the same advantages of live attenuated vaccines (cell-mediated responses, more robust immunity) and fewer of the disadvantages (low or nonexistent reversion potential and moderate production times). • DNA vaccines aim to deliver selected genetic material from an infectious agent into host cells as a means for host-based gene expression and immune activation. • RNA vaccines work by introducing an mRNA sequence encoding for a disease specific antigen. These vaccines are faster and cheaper to produce than traditional vaccines, and a RNA based vaccine is also safer for the patient, as they are not produced using infectious elements.