Vaccine Types and mRNA Vaccines

• Vaccines are a key tool in preventing infectious diseases.
• There are various types, each with unique mechanisms and applications.

Vaccine Types

• Live, attenuated vaccines use weakened forms of the pathogen (MMR, Nasal Flu, Polio).
• Inactivated vaccines use killed pathogens (Polio, cellular Pertussis).
• Subunit vaccines use specific components of the pathogen (Pertussis, Hepatitis B).
• Toxoid vaccines use inactivated toxins produced by the pathogen (Diphtheria, Tetanus, Pertussis).
• Conjugate vaccines link polysaccharides to proteins to enhance immunogenicity (HiB, Pneumococcal, Meningococcal).
• Recombinant vector vaccines use viral or bacterial vectors to deliver pathogen genes (HPV, SARS-CoV-2).
• mRNA vaccines deliver genetic instructions for the body to produce pathogen proteins (SARS-CoV-2).

mRNA Vaccines

• mRNA vaccines work by delivering messenger RNA that instructs cells to produce viral proteins like the spike protein for SARS-CoV-2.
• The mRNA is encapsulated in lipid nanoparticles to facilitate entry into cells.
• Once inside, the mRNA is translated into the viral protein, which is then processed and presented on the cell surface to stimulate an immune response.
• This immune response includes the activation of cytotoxic T cells and the production of antibodies.

Recombinant Vector Vaccines

• Recombinant vector vaccines use a harmless virus or bacterium to carry genetic material encoding pathogen antigens into the body.
• Upon entry into cells, the vector expresses the foreign gene, resulting in the production of antigens that trigger an immune response.
• This process elicits antibody production, antigen presentation, and CTL-mediated killing of infected cells.

Coronavirus Vaccine Types

• Protein-based vaccines use purified spike protein, which is injected to stimulate antibody production.
• Viral vector vaccines use a modified virus to deliver genetic instructions for spike protein production, leading to immune system response.
• mRNA vaccines contain mRNA coding for the spike protein, which, when translated, prompts the immune system to produce antibodies.

Historical Overview of Vaccines

• 18th Century: Smallpox vaccine (1798).
• 19th Century: Rabies vaccine (1885).
• Early 20th Century: Diphtheria (1923), Tetanus (1926), Pertussis (1926), Influenza (1936), Typhus (1938).
• Mid to Late 20th Century: Lyme, Cholera, Hepatitis C, Polio, Japanese encephalitis, tick-borne encephalitis, hepatitis A, measles, mumps, rubella, Adenovirus, typhoid, varicella, rotavirus.

Modern Vaccines

• Include vaccines for Pneumococcal, Meningococcal, Hib, Hepatitis B, Typhoid, acellular Pertussis, Anthrax, cold-adapted Flu, Rotavirus, and Zoster.
• Current vaccines target HPV and SARS-CoV-2.

DPT and DTaP Vaccines for Bacterial Diseases

• DPT vaccine contains toxoids for Diphtheria and Tetanus, and whole killed cells for Pertussis.
• The DTaP vaccine, introduced in the 1990s, uses acellular proteins for Pertussis.
• Pertussis components include pertussis toxoid, outer-membrane proteins (Pertactin, FHA), and fimbriae proteins (types 2 and 3).
• There can be moderate side effects in 20% of cases (discomfort, convulsions), with rare occurrences of hearing loss or brain damage from DPT vaccines.

Conjugate Polysaccharide Vaccines

• Conjugate vaccines, such as HiB, Pneumococcal, and Meningococcal vaccines, link polysaccharide antigens to proteins for better immune recognition.
• The B-cell recognizes the polysaccharide part, while presenting the protein part to the T-cell to allow for recognition that would not occur with polysaccharides only.
• Memory B cells and T-cells are produced to aid a faster immune response to the polysaccharide.

Meningococcal Vaccines

• Meningococcal disease can result in meningitis and blood infections, with a significant mortality rate even when treated promptly.
• Survivors may experience disabilities, including hearing loss and brain damage.
• Polyvalent vaccines that target serogroups A, C, Y, and W135, are effective for people over 2.
• Polyvalent conjugate vaccines can be used as early as 2 months, followed by a dose at 11-12 years and 16 years.
• Serogroup B vaccines (MenB) are subunit vaccines composed of Factor H binding protein (fHBP), Neisserial adhesin A (NadA), Neisseria heparin binding antigen (NHBA), and PorA.
• The MenB vaccines were developed by Novartis (Bexsero) and Pfizer (Trumenba) and approved in 2013-2014.

Haemophilus influenzae

• Haemophilus influenzae are Gram-negative, rod-shaped, non-motile bacteria.
• In the early 1980s, they caused around 20,000 cases a year, mainly in children under 5.
• They are responsible for epiglottitis, pneumonia, and meningitis.
• Hib conjugate vaccines have significantly decreased prevalence, from 23.8 per 100,000 in 1991 to 0.92 cases per 100,000 in 1996.
• The PRP capsule prevents C3b binding/phagocytosis.
• The vaccine is a conjugated vaccine, consisting of a polysaccharide bound to a protein.

Pneumococcal Conjugate Vaccines

• Prevnar 7: Wyeth Heptavalent conjugate vaccine released in 2000, contained 7 serotypes (4, 6B, 9V, 14, 18C, 19F, 23F).
• The 7 serotypes covered 80% of disease.
• Synflorix: GlaxoSmithKline Decavalent conjugate vaccine released in 2009, contained 10 serotypes (1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, 23F).
• Prevnar 13: Pfizer Tridecavalent conjugate vaccine released in 2010, contained 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F).

Adjuvants

• Adjuvants boost the immune response and enhance antigen delivery.
• Common adjuvants include Alum (Th2), saponins (QuilA & QS-21), squalene (MF59 & AS03), virosomes, and liposomes.

Liposomenes

• Can incorperate proteins, glycolopids and lipds
• Can also electrostaticly bind oligonucleitides

Reasons Why Vaccines Don't Alway Work

• Vaccines may elicit the wrong immune response.
• This includes TB (Humoral), Salmonella, Cholera (Needs to be mucosal.
• There can be potential side effects, allergic reactions, and in some cases, worsening of disease (RSV, Chlamydia).