Exam 3_ Part 1

Vaccine History and Societal Impact

• Vaccination mobilizes the host immune system to prevent disease.
• Vaccination helps break the chain of disease transmission.
• Variolation, a practice of deliberate nasal inoculation with dried smallpox scabs, was used in China in the 11th century.
• Edward Jenner, in 1796, was the first to use cowpox to protect against smallpox.
• The smallpox vaccine was a major contributor to the eradication of smallpox, saving an estimated ~5 million lives annually.
• As soon as the smallpox vaccine became available, concerns arose about developing "cow parts" following vaccination.
• The World Health Organization estimates that current immunization programs save 2-3 million lives annually.
• Vaccine inequality exists, with developing nations often having limited access or less effective vaccines for certain diseases like rubella, measles, and rotavirus.

Passive vs. Active Immunization

• Passive immunization involves administering the products of the immune response, such as antibodies, providing short-term protection.
• Active vaccination involves administering a modified form of the pathogen or its derivatives, inducing long-term immunity.

Natural Passive Immunization

• IgG from maternal circulation is passively transmitted to the fetus in utero through the placenta.
• IgG levels decline slowly after birth.
• Vaccination of pregnant women can protect the baby during the first 6 months of life.

Respiratory Syncytial Virus

• Respiratory Syncytial Virus (RSV) can cause severe respiratory illness, such as bronchiolitis or pneumonia.
• Nearly all children become infected with RSV by the age of 2.
• 1-2% of children with RSV require hospitalization, which may involve oxygen, intubation, or mechanical ventilation.

Prevention of RSV Disease

• Active Vaccine:
  • ABRYSVO (introduced in 2023) is a recombinant prefusion F protein vaccine given during pregnancy.
  • Clinical trials demonstrated its efficacy in protecting infants from lower respiratory tract illness.
  • Recommended for use during RSV season at 32-36 weeks gestation.
• Artificial Passive Immunity:
  • Nirsevima (introduced in 2023) is a monoclonal antibody approved for infants.

Artificial Passive Immunization: Convalescent Serum

• Convalescent serum, rich in antibodies from individuals who have recovered from a disease, has historically been used to treat emerging infectious diseases.
• In the 1960s, a virologist who contracted Lassa virus was successfully treated with plasma from a recovered nurse.

Convalescent Plasma and Monoclonal Antibodies for COVID-19 Treatment or Prevention

• Plasma is the liquid portion of blood remaining after the cells are removed.
• Monoclonal antibodies, targeting specific epitopes, can block infection.
• Both convalescent plasma and monoclonal antibodies were employed in the early stages of the COVID-19 pandemic, before the emergence of resistant variants.

Attenuated Vaccines

• Replication-competent, attenuated vaccines induce a memory immune response similar to natural infection.
• Examples of attenuated vaccines: Oral Polio Vaccine (OPV)
• Attenuated vaccines are contraindicated in pregnancy and immunocompromised individuals due to the need for an immune response to clear the infection.
• It is safe to administer attenuated vaccines to people living with HIV with CD4 T cell count > 200 cells/mm3.
• OPV was attenuated by passing the virus in monkey kidney cells and replicates in gut-associated tissues.
• Attenuation of poliovirus neurovirulence often involves changing a few nucleotides in the 5'UTR of viral RNA.
• In rare cases, the vaccine-attenuating mutations can revert to the original form of the virus (wild-type) leading to paralytic poliomyelitis.

Inactivated Vaccines

• Inactivated vaccines use chemical procedures to inactivate the pathogen.
• Inactivated vaccines are safer for pregnant and immunocompromised individuals.
• Examples of inactivated vaccines: Sinovac COVID-19 vaccine CoronaVac, Inactivated influenza vaccines.

The Tragedy of the RSV Vaccine Candidate

• A formalin-inactivated RSV vaccine candidate tested in the 1960s resulted in enhanced respiratory disease (ERD) in vaccinated children.
• 80% of children who received the vaccine experienced serious disease compared to 5% of placebo recipients.
• The vaccine primed the immune system for a severe response, leading to increased illness upon natural RSV infection.
• The ERD likely resulted from a TH2-driven immune response characterized by pulmonary eosinophilia and non-neutralizing antibodies.
• Correlates of protection for RSV likely involve TH1-driven immune responses and neutralizing antibodies against the F protein.

Influenza Vaccines

• Inactivated influenza vaccines (IIV) are recommended for everyone > 6 months old.
• Live attenuated influenza vaccine (LAIV) is available as a nasal spray for ages 2-49 in immunocompetent, non-pregnant individuals.
• Influenza virus HA binds to sialic acid for entry, while NA cleaves HA-sialic acid for viral release.
• IIV is the cornerstone of public health in the US, formulated annually with 4 strains of influenza virus.
• Correlates of protection against influenza involve serum antibodies to HA and NA.
• Widespread vaccination with IIV reduces mortality and illness in older adults.
• IIV reduces transmission between animals in a guinea pig model.
• There is a 6 month delay for pandemic influenza vaccine production, highlighting the need for better rapid manufacturing methods.

mRNA vaccines

• mRNA vaccines use DNA encoding the antigen of interest, packaged into lipid nanoparticles.
• The COVID-19 mRNA vaccines (Pfizer-BioNTech and Moderna) encode for the pre-fusion spike protein of SARS-CoV-2.
• mRNA vaccines are injected into muscle, where DCs take up the mRNA and synthesize the viral antigen, triggering an immune response.
• mRNA COVID-19 vaccines reduce disease severity upon SARS-CoV-2 infection.
• The Pfizer-BioNTech COVID-19 vaccine (BNT162b2) has demonstrated long-term memory B and T cell formation that offer protection against severe disease.
• Pfizer-BioNTech and Moderna mRNA vaccines offer a rapid and scalable manufacturing process, excellent safety profile, and immunogenicity.
• They are a promising new class of vaccine with the potential to address future infectious disease threats.

Characteristics of Live Attenuated Vaccines

• These vaccines can reversion back to a virulent pathogen
• They are generated by passaging a pathogen in human cells

Adjuvants

• These adjuvants are added to vaccines to enhance antigen presentation

High-Risk Groups for Seasonal Influenza

• A woman in her second trimester of pregnancy is considered high-risk
• A 7-month old male living in Arizona is considered high-risk
• A 72-year-old female in relatively good health is considered high-risk

Herd Immunity

• This concept is known as herd immunity

Inactivated Vaccines

• Inactivated vaccines are composed of an infectious agent without the ability to replicate
• Inactivated vaccines are composed of toxoids
• Inactivated vaccines are composed of capsular polysaccharides

Recombinant Subunit Vaccine

• This type of vaccine is called a recombinant subunit vaccine

mRNA-Based Vaccines

• The COVID-19 vaccine developed by Pfizer/BioNTech and Moderna, Inc. are mRNA-based vaccines

Explore the profound history and societal implications of vaccination, from early practices like variolation in China to Edward Jenner's pioneering work with the smallpox vaccine. This quiz covers key historical milestones, the concept of active versus passive immunization, and current global vaccine equity issues.