Production of virus-like particle (VLP) vaccines

for influenza

Rodrigo Garca Ortega A00889617

Elsa Gmez Escobar A00987704

Javier Ramrez Carbajal A00889696

Alfredo Tobn Avils A01203104

INTRODUCTION

Influenza is an acute, infectious, respiratory disease.

Caused by orthomyxovirus family (retroviruses).

Type A and B // Flu epidemics every year.

Image 1. Influenza 3D representation

INTRODUCTION

Several strains have become epidemics:

Spanish influenza (H1N1) of 1918-1920

Asian flu (H2N2) of 1957-1958

Hong Kong flu (H3N2) of 1968-1969

Bird flu global spread (H5N1) of 2003-2010

Swine flu (H1N1) of 2009

Image 2. Influenza H1N1 swine flu strain

INTRODUCTION

Image 3. Mutation of influenza virus

INTRODUCTION

Such diseases // Huge threat to public health.

Because of:

Seasonal exposure

Fast rate of dispersion

Fast rate of mutation

Slow-rate of vaccine production.

INTRODUCTION

Prevention is easily exceeded by dispersion and exposure

of the virus.

Mutation cannot be avoided.

Is there a faster way to produce vaccines?

Image 4. Vaccines

INTRODUCTION

Traditional vaccines are produced in chicken eggs.

Live-attenuated

Inactivated

900 million eggs = 300 million doses

Perishable foods.

Antigenic properties are lost

New methodologies?

Image 5. Egg

INTRODUCTION

Virus-like particles are:

multiprotein structures that mimic the organization and conformation of authentic native viruses but lack the viral genome, potentially yielding safer and cheaper vaccine candidates

.

Image 6. Virion (left) and its corresponding VLP (right)

BACKGROUND

Two VLP vaccines are FDA approved:

Hepatitis B vaccine / / Human papillomavirus (HPV)

vaccine

For the hepatitis B vaccine, only 22ng of the VLP protein is

used per dose.

Image 8. Gardasil HPV vaccine

Image 7. Recombivax HB

BACKGROUND

Other VLP vaccine production cases have been published:

West Nile virus vaccine (2010)

Chikungunya virus vaccine (2010)

Respiratory syncytial virus vaccine (2008)

Human Immunodeficiency virus (HIV) vaccine (2008)

VLP vaccines for influenza viruses:

Influenza A subtype H1N1

Influenza A subtype H5N1

} Phase II of clinical trias

BACKGROUND

Different companies have developed VLP vaccines:

OBJECTIVES

Analyze the methodology to produce VLPs for

influenza vaccines

Propose a vaccine for the influenza A virus

swine flu strain

Current methodology

Viral RNA extraction

RT-PCR Clonation

in E. Coli

Baculovirus transfection

SF9 cell protein expression

Purification

VLP VACCINE CANDIDATE

VLP VACCINE CANDIDATE

VLP VACCINE CANDIDATE

RESULTS AND DISCUSSION

The method proposed could be held in less than a week.

If a oligonucleotide synthetizer is available

The tests held to prove the effectiveness of the vaccine are

apart from this time.

Passing from months to weeks in the production of a vaccine is

excellent.

Image 9. Syringe

RESULTS AND DISCUSSION

In spite of the appearance of VLP

most of these vaccines are [still] being

produced using chicken eggs, while a

few manufacturers are using cell culture

technology for vaccine production

This is the biggest barrier to toss, the existing facilities for

egg-based vaccines.

CONCLUSIONS

Eggs as vaccine culture media is complicated and a risk that

should be avoided.

The high cost of eggs is eliminated and substituted by a lower

cost and higher yield insect cells.

Fast vaccines are key for the maintenance of the public order.

CONCLUSIONS

Virus-like particles (VLP) vaccine production must be

promoted

Governmental grants

Private investments

What is the point of having preventive methods that

become available when the problem has already spread?

Image 10. Money is important

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