Vaccine Development and Platforms

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Questions and Answers

What is the purpose of adding adjuvants to some vaccines?

To reduce side effects of the vaccine

To enhance the immune response (correct)

To replace the vaccine antigen

To increase the vaccine's shelf life

Which population benefits the most from the immunity of others in the context of influenza vaccination?

Pregnant women

Children under the age of 5

Healthcare providers

Older adults (correct)

What was significant about the mRNA-based vaccines developed for COVID-19?

They used a traditional viral inactivation method

They were based on a new platform never licensed before (correct)

They were only effective in children

They required a longer development period than typical vaccines

What model was used to demonstrate the reduction of influenza transmission through vaccination?

Guinea pig model Signup and view all the answers

What age group is eligible for the inactivated influenza vaccine (IIV)?

Individuals over six months of age Signup and view all the answers

What is the primary method used for growing the virus in the production of the inactivated influenza vaccine?

Embryonated chicken eggs Signup and view all the answers

What is the main correlate of protection for the influenza vaccine?

Serum antibodies to HA and NA Signup and view all the answers

Which age group has a more effective high-dose influenza vaccine option?

Patients aged 65 and older Signup and view all the answers

What is the main challenge faced in developing a pandemic influenza virus vaccine?

Production time exceeding six months Signup and view all the answers

How much did the flu vaccine reduce the risk of children’s admission to the pediatric intensive care unit during certain flu seasons?

74% Signup and view all the answers

What is the typical number of doses of the influenza vaccine manufactured each year in the US?

75-100 million Signup and view all the answers

What approach is used to inform strain selection for the seasonal influenza vaccine?

Surveillance of Southern Hemisphere flu patterns Signup and view all the answers

What type of vaccine option is available for patients aged 65 and older apart from the high-dose vaccine?

Standard-dose IIV with an adjuvant Signup and view all the answers

What was the main issue associated with the RSV vaccine candidate developed in the 1960s?

It caused enhanced respiratory disease in vaccinated children. Signup and view all the answers

Which vaccine strategy is employed to minimize the risk of vaccine-derived paralytic poliomyelitis?

Utilizing an inactivated polio vaccine. Signup and view all the answers

What property of the new Oral Polio Vaccine (OPV) allows for a reduced ability to acquire mutations?

Precision attenuation through molecular biology. Signup and view all the answers

What was a key characteristic of the inactivated vaccines like the Sinovac CoronaVac?

They are safe for immunocompromised individuals. Signup and view all the answers

Which component of the influenza virus is responsible for gaining entry into host cells?

Hemagglutinin. Signup and view all the answers

How does the antibody response relate to enhanced respiratory disease in the 1960s RSV vaccine trial?

It caused production of non-neutralizing antibodies. Signup and view all the answers

Which is a recommended vaccination strategy for influenza in individuals older than 6 months?

Inactivated influenza vaccination. Signup and view all the answers

Which cytokine profile is likely involved in correlates of protection against RSV infection?

Secretion of Th1 cytokines and neutralizing antibodies. Signup and view all the answers

What is a potential consequence of low vaccination coverage for polio?

Higher likelihood of vaccine-derived poliovirus cases. Signup and view all the answers

What is a major characteristic of replication competent, attenuated vaccines?

They stimulate a memory immune response through pathogen replication. Signup and view all the answers

What is a risk associated with attenuated vaccines?

They can revert to a virulent form of the virus. Signup and view all the answers

Which of the following describes the Oral Polio Vaccine's administration method?

It is delivered orally in sugar drop form. Signup and view all the answers

In what way did the 1960s RSV vaccine candidate highlight the need for vaccine correlates of protection?

It triggered enhanced respiratory disease in some vaccinated individuals. Signup and view all the answers

Which patient population should avoid live attenuated vaccines?

Pregnant women and those with immunodeficiencies. Signup and view all the answers

How do mRNA vaccines like Pfizer and Moderna elicit an immune response?

They use lipid nanoparticles to deliver mRNA encoding viral proteins. Signup and view all the answers

What effect did the Oral Polio Vaccine have on poliomyelitis in the U.S.?

It eliminated poliomyelitis but not the virus background. Signup and view all the answers

What is a common characteristic of inactivated vaccines compared to attenuated ones?

They cannot cause disease in immunocompromised individuals. Signup and view all the answers

What was a significant outcome of the alteration made to the poliovirus in vaccines?

It limited the ability to cause paralysis. Signup and view all the answers

Why are new inactivated influenza vaccines urgently needed?

Antigenic drift and shift in the virus necessitate updates. Signup and view all the answers

What is a contraindication for receiving the COVID-19 vaccine?

History of a severe allergic reaction after a previous dose Signup and view all the answers

Which group of individuals is considered safe to receive inactivated vaccines?

Immunocompromised individuals Signup and view all the answers

What immune response is desired for an inactivated RSV vaccine candidate?

TH1 immune response Signup and view all the answers

What is the main benefit of the COVID-19 mRNA vaccines?

They encode the Spike protein and enhance immune response. Signup and view all the answers

Which statement about the Oral Polio Vaccine (OPV) is true?

It protects against paralysis and leads to gut immunity. Signup and view all the answers

What is a significant impact of COVID-19 vaccinations since their rollout?

They have averted an estimated 14 million deaths. Signup and view all the answers

Which vaccine strategy is recommended for individuals aged 65 and older?

4-fold antigen or adjuvant vaccines Signup and view all the answers

How do lipid nanoparticles enhance the COVID-19 mRNA vaccine?

They stabilize the mRNA to avoid degradation. Signup and view all the answers

What challenges are faced in developing new inactivated influenza vaccines?

Variability in seasonal virus strains Signup and view all the answers

What is the primary purpose of using mRNA vaccine platforms in response to COVID-19?

To rapidly produce a vaccine against emerging infectious threats Signup and view all the answers

In the context of vaccine development, what does the term 'attenuated' primarily refer to?

Vaccines that contain live viruses with reduced pathogenicity Signup and view all the answers

Why is widespread vaccination of children particularly important in reducing influenza-related mortality among older adults?

Children's vaccinations directly increase adult immunity levels Signup and view all the answers

What significant historical context prompted the accelerated development of the COVID-19 mRNA vaccine?

The emergence of SARS-CoV-2 as a pandemic threat Signup and view all the answers

What is a major advantage of using attenuated vaccines over inactivated vaccines?

They can stimulate a stronger and longer-lasting immune response. Signup and view all the answers

What was the primary reason the 1960's RSV vaccine candidate caused enhanced respiratory disease?

It generated a non-neutralizing antibody response. Signup and view all the answers

For which group of patients is the administration of live attenuated vaccines contraindicated?

Pregnant women and immunodeficient patients. Signup and view all the answers

Which platform is primarily utilized for the development of the Pfizer and Moderna COVID-19 vaccines?

mRNA lipid nanoparticle platform. Signup and view all the answers

What is a notable characteristic of the Sabin Oral Polio Vaccine (OPV)?

It can circulate and persist in the environment. Signup and view all the answers

How does attenuation of the poliovirus typically occur in the vaccine development process?

By passaging it in animal cell cultures. Signup and view all the answers

Which of the following is a potential challenge with replication competent, attenuated vaccines?

They can revert to a virulent form. Signup and view all the answers

What was one of the outcomes from the changes made to the poliovirus for the development of the vaccine?

Loss of neurovirulence capable of causing paralysis. Signup and view all the answers

Which group of individuals is recommended to receive high-dose influenza vaccines?

Individuals aged 65 and older. Signup and view all the answers

What is the primary reason why vaccines were not available until after the peak of the 2009 influenza pandemic?

Six months is too long for production Signup and view all the answers

Which influenza vaccine shows a 24% higher effectiveness in individuals over 65 years of age?

High-dose vaccine with 4-fold more antigen Signup and view all the answers

What is the most common method for producing the inactivated influenza vaccine?

Grow in embryonated chicken eggs Signup and view all the answers

How many doses of inactivated influenza vaccine are typically produced in the United States each year?

75-100 million Signup and view all the answers

What correlates with the protection provided by the influenza vaccine?

Serum antibodies to HA and NA proteins Signup and view all the answers

What factor influences the selection of strains for the seasonal influenza vaccine?

Surveillance of the Southern Hemisphere Signup and view all the answers

Which of the following statements about the effectiveness of the flu vaccine during specific seasons is accurate?

The flu vaccine reduces children's risk of hospitalization by 74%. Signup and view all the answers

Which vaccine strategy is utilized for patients aged 65 and older who receive inactivated influenza vaccines?

High-dose vaccines or standard-dose with adjuvants Signup and view all the answers

What critical risk is associated with low vaccination coverage for polio?

Higher likelihood of vaccine-derived paralytic poliomyelitis. Signup and view all the answers

Which statement accurately describes the risk associated with live attenuated vaccines?

They pose a risk of reverting to a virulent form in immunocompromised individuals. Signup and view all the answers

What immune response is considered desirable for an effective inactivated RSV vaccine candidate?

Production of neutralizing antibodies to the F protein. Signup and view all the answers

What potential issue is associated with the induction of a TH2 immune response when using an inactivated RSV vaccine candidate?

It triggered enhanced disease upon infection. Signup and view all the answers

Which of the following describes a unique characteristic of the New Oral Polio Vaccine?

It has decreased capability of mutation necessary for replication. Signup and view all the answers

Which age group is specifically mentioned as being eligible for a high-dose influenza vaccine?

Individuals aged 65 years and older. Signup and view all the answers

In what way does the design of COVID-19 mRNA vaccines influence immune response?

They encode Spike protein in its pre-fusion conformation to stimulate a robust response. Signup and view all the answers

What key issue emerged from the clinical trials of the RSV vaccine candidate in the 1960s?

It caused enhanced respiratory disease in a significant proportion of participants. Signup and view all the answers

What is a major concern with using live attenuated vaccines in specific populations?

Potential for severe adverse reactions in immunocompromised individuals. Signup and view all the answers

What is a major consequence of not achieving sufficient vaccination coverage for polio?

Increased risk of vaccine-derived paralytic poliomyelitis. Signup and view all the answers

Which statement about the safety of COVID-19 vaccines in immunocompromised individuals is true?

They are safe but their efficacy may be reduced. Signup and view all the answers

How does the mechanism of action for the influenza virus's hemagglutinin contribute to viral infectivity?

It facilitates entry into the host cell by binding sialic acid. Signup and view all the answers

What is a primary benefit of the Oral Polio Vaccine (OPV)?

It induces both mucosal and systemic immunity. Signup and view all the answers

What is a defining feature of inactivated vaccines like the Sinovac COVID-19 vaccine?

They retain full antigenicity but may compromise efficacy. Signup and view all the answers

Which cytokine profile has been implicated in the undesirable immune responses observed with the RSV vaccine candidate?

Elevation of TH2 cytokines. Signup and view all the answers

What critical role do lipid nanoparticles play in COVID-19 mRNA vaccines?

They facilitate uptake of the mRNA by cells. Signup and view all the answers

What is the primary goal of attenuating a vaccine pathogen?

To ensure safety while eliciting an immune response. Signup and view all the answers

What has been a significant barrier to the development of a safe RSV vaccine?

Severe adverse reactions in initial trials. Signup and view all the answers

Study Notes

Vaccine Development

Attenuated vaccines use a weakened form of a pathogen that replicates and stimulates the immune system (e.g., oral polio vaccine (OPV)).
Inactivated vaccines are chemically treated pathogens that cannot replicate but still elicit an immune response (e.g., inactivated polio vaccine (IPV)).
Inactivated vaccines are safer for pregnant and immunocompromised individuals.

Vaccine Platforms

Attenuated vaccines are not safe for pregnant women or people with weakened immune systems.
The OPV was attenuated using monkey kidney cells and replicates in the gut.
It causes transient gut immunity and lasting systemic immunity.
Oral poliovirus is contraindicated in people living with HIV with CD4 T cell counts below 200 cells/mm3.
Poliovirus mutations are found in the 5’UTR of viral RNA.
OPV causes 1 paralytic case for every 1.4 million doses administered but was replaced with IPV in 2000.
OPV can revert to a virulent form.
Inactivated vaccines are made with chemically treated pathogens, often using formaldehyde, beta-propiolactone, or nonionic detergents.

Respiratory Syncytial Virus (RSV)

There is currently no available active vaccine for RSV in children.
An inactivated RSV vaccine candidate in the 1960s caused enhanced respiratory disease (ERD) which led to death in some children.
The vaccine elicited pulmonary eosinophilia due to CD4+ T cells secreting TH2 cytokines.
The vaccine triggered the production of non-neutralizing antibodies.
Correlates of protection likely involve CD4+ T cells secreting TH1 cytokines and neutralizing antibodies to the F protein.

Influenza Vaccine

Influenza vaccines are recommended for everyone older than 6 months.
The inactivated influenza vaccine (IIV) is the cornerstone of public health.
The influenza A and B virus hemagglutinin (HA) binds sialic acid to gain entry to host cells.
The influenza A and B virus neuraminidase (NA) cleaves HA-sialic acid for virus release.
Influenza vaccine effectiveness against symptomatic illness is carefully monitored each season.
The live attenuated influenza vaccine (LAIV) is a nasal spray vaccine available for ages 2-49 in immunocompetent, non-pregnant individuals.
The IIV is only available after 6 months of age, which makes vulnerable populations reliant on community immunity.
High-dose IIV (4-fold increased antigen) is more effective for individuals over 65 years old.
Vaccination of children with the IIV reduces mortality and illness in older adults.

COVID-19 Vaccine

Two mRNA lipid nanoparticle vaccines, Pfizer/BioNTech and Moderna, are available for use in individuals over 6 months of age.
mRNA vaccines encode the Spike protein and trigger a robust memory B and T cell response.
Both mRNA COVID-19 vaccines are safe for individuals with weakened immune systems.
These vaccines have been estimated to have averted at least 14 million deaths.

Take Home Messages

Attenuated vaccines trigger mucosal and systemic immunity.
Induction of a TH2 immune response to an inactivated vaccine may increase the risk of disease.
Inactivated vaccines stimulate an immune response but are safe for pregnant and immunocompromised individuals.
The IIV is formalin-inactivated and confers protection from influenza.
Vaccination with COVID-19 mRNA vaccines triggers a robust T cell response, and lipid nanoparticles enhance uptake by cells.

Attenuated Vaccines

Attenuated vaccines are "live" vaccines that contain a weakened form of the pathogen, but can replicate within the host.
They induce a long-lasting, systemic immune response, including memory T cells.
Examples include the Oral Polio Vaccine (OPV) and the measles, mumps, rubella (MMR) vaccine.
Attenuated vaccines are contraindicated in pregnant women and individuals with compromised immune systems, because they require an immune response to clear the pathogen.
Attenuated vaccines can revert to virulent forms, such as the 2022 case of paralytic poliomyelitis in New York caused by a vaccine-derived poliovirus.

Inactivated Vaccines

Inactivated vaccines use pathogens that have been killed, rendered unable to replicate, but still retain their antigens.
Examples include the influenza vaccine and the Salk polio vaccine.
These vaccines are generally safe for pregnant women and people with compromised immune systems, but they may be less effective than attenuated vaccines.
Inactivated vaccines rely on chemical processes (formaldehyde, beta-propiolactone, or nonionic detergents).
Inactivated vaccines are unable to replicate but do stimulate an immune response.

RSV (Respiratory Syncytial Virus) Vaccine

1960s Trial: A formalin-inactivated RSV vaccine candidate resulted in enhanced respiratory disease (ERD), including severe illness and death in children.
Cause: It triggered a TH2-mediated immune response with non-neutralizing antibodies, exacerbating disease.
Correlates of protection involve neutralizing antibodies to the F protein and TH1-mediated immune response.

Influenza Vaccines

Influenza vaccines are recommended for everyone over 6 months of age.
Inactivated influenza vaccine (IIV) is the primary vaccine, administered intramuscularly.
Live-attenuated influenza vaccine (LAIV) is available as a nasal spray for individuals 2-49 years with competent immune systems, non-pregnant.
Challenges:
- Effectiveness varies seasonally and depends on strain matches to circulating strains.
- Production can take months, making it difficult to develop pandemic influenza vaccines readily.
Older Adults:
- High-dose IIV (4-fold greater antigen) is recommended for those over 65.
- Standard-dose IIV with an adjuvant (to enhance the immune response) is another option.

COVID-19 mRNA Vaccines

Pfizer/Moderna vaccines:
- Encode the spike protein of the SARS-CoV-2 virus.
- When administered, the mRNA enters cells and instructs them to produce the spike protein.
- Spike protein triggers a robust B-cell and T-cell immune response.
- Lipid nanoparticles enhance cellular uptake of the mRNA.
Efficacy/Safety:
- High rates of protection against severe COVID-19, hospitalization, and death.
- Safe for immunocompromised individuals.
- Contraindications: History of severe allergic reactions to a previous dose or vaccine component.

Vaccine Importance

Vaccinations, not vaccines, save lives.
Vaccine policies are crucial for public health.
Vaccines are a cornerstone of modern medicine, significantly reducing morbidity and mortality from preventable diseases.

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Description

This quiz covers essential concepts in vaccine development, focusing on the differences between attenuated and inactivated vaccines. It explores the safety profiles of these vaccines for various populations and details the mechanisms and implications for immune response. Test your knowledge on vaccine types, risks, and their applications in immunization.