mRNA Vaccine Against Avian Flu—A

Proposal From RNA Therapeutics

Background
Avian influenza refers to infection of birds with avian influenza Type A viruses. These viruses
occur naturally among wild aquatic birds worldwide and can infect domestic poultry and other
bird and animal species. Wild aquatic birds can be infected with avian influenza A viruses in
their intestines and respiratory tract, but usually do not get sick. However, avian influenza A
viruses are very contagious among birds and some of these viruses can sicken and even kill
certain domesticated bird species including chickens, ducks, and turkeys.

Infected birds can shed avian influenza A viruses in their saliva, nasal secretions, and feces.
Susceptible birds become infected when they have contact with the virus as it is shed by infected
birds. They also can become infected through contact with surfaces that are contaminated with
virus from infected birds.

Avian influenza A viruses are classified into the following two categories: low pathogenic avian
influenza (LPAI) A viruses, and highly pathogenic avian influenza (HPAI) A viruses. The
categories refer to molecular characteristics of a virus and the virus’ ability to cause disease and
mortality in chickens in a laboratory setting. Infection of poultry with LPAI viruses may cause
no disease or mild illness (such as ruffled feathers and a drop in egg production) and may not be
detected. Infection of poultry with HPAI viruses can cause severe disease with high mortality.
Both HPAI and LPAI viruses can spread rapidly through poultry flocks. However, some ducks
can be infected without any signs of illness.

Domesticated birds (chickens, turkeys, etc.) may become infected with avian influenza A viruses
through direct contact with infected waterfowl or other infected poultry, or through contact with
surfaces that have been contaminated with the viruses.

Infection of poultry with LPAI viruses may cause no disease or mild illness and may only cause
mild signs (such as ruffled feathers and a drop in egg production) and may not be detected.
Infection of poultry with HPAI viruses can cause severe disease with high mortality. Both HPAI
and LPAI viruses can spread rapidly through flocks of poultry. HPAI virus infection in poultry
(such as with HPAI H5 or HPAI H7 viruses) can cause disease that affects multiple internal
organs with mortality up to 90% to 100%, often within 48 hours. Some ducks can be infected
without any signs of illness.

Avian influenza outbreaks are of concern in domesticated birds for several reasons:
 the potential for low pathogenic H5 and H7 viruses to evolve into highly pathogenic
viruses
 the potential for rapid spread and significant illness and death among poultry during
outbreaks of highly pathogenic avian influenza
  the economic impact and trade restrictions from a highly pathogenic avian influenza
outbreak
 the possibility that avian influenza A viruses could be transmitted to humans

When H5 or H7 avian influenza outbreaks occur in poultry, depopulation (or culling, also called
“stamping out”) of infected flocks is usually carried out. In addition surveillance of flocks that
are nearby or linked to the infected flock(s), and quarantine of exposed flocks with culling if
disease is detected, are the preferred control and eradication methods.

Market
Global Avian Influenza Vaccine Market is expected to register a CAGR of 7.25% to reach USD
735.22 Million by 20251. Avian influenza, also known as bird flu, is a viral infection that spreads
from bird to bird and can infect other animals or humans also. There are different strains of avian
influenza, causing the infection, but H5N1 is the most common virus strain affecting poultry
animals.
The segment study of the global avian influenza vaccine market is done by application and
strain. The strain-based segments of the avian influenza market are H9, H5, and H7. The
availability of vaccines to combat different strains can favor the market growth in the near future.
The application-based segments of the avian influenza vaccine market are goose and duck,
chicken, and turkey. The chicken segment can earn high revenue for the market2.

Competitors
Major Companies in the worldwide Avian Influenza Vaccine Market are:

 Boehringer Ingelheim International GmbH (Germany)

 Ceva (US)
 Guangdong Wenshi Dahuanong Biotechnology Co. Ltd (China)
 Avimex Animal Health (Mexico),
 FATRO S.P.A. (Italy)
 Zoetis (US)
 CAVAC (South Korea)
 PT Japfa Comfeed Indonesia Tbk (Indonesia)
 Merck Animal Health (US)
 Tianjin Ringpu Bio-Technology Co., Ltd (China)
 Chengdu Tech-bank Biological Products Co., Ltd (China)
 QYH BIOTECH COMPANY LIMITED (China)
 Medion (Indonesia)
 JOVAC (Jordan)
Some enterprises are observed to purchase new facilities to boost their vaccine production
capacity, and open new research facilities that can add to the market rise. Lately, few players are

1
https://www.marketresearchfuture.com/reports/avian-influenza-vaccine-market-8769
2
https://www.globenewswire.com/news-release/2021/02/23/2180797/0/en/Avian-Influenza-Vaccine-Market-Size-
to-Cross-USD-735-22-Million-by-2025-at-a-CAGR-of-7-25-Predicts-Market-Research-future-MRFR.html
reported to receive conditional license for the study and synthesis of avian influenza vaccine.
This can also underline the market expansion by 2025.

Vaccine Plan
H5N1 (Most common and Indonesia), H5N2(Taiwan) and H5N8 virus types are the target. Exact
selection will made after receiving advise from industry experts and epidemiologists, particularly
from Pakistan.

Target Protein for H5N1:

The amino acid sequence of H5N1 nucleoprotein is:
GSPGILMASQGTKRSYEQMETGGERQNATEIRASVGRMVGGIGRFYIQMCTELKLSDQE
GRLIQNSITIERMVLSAFDERRNRYLEEHPSAGKDPKKTGGPIYRRRDGKWVRELILYDK
EEIRRIWRQANNGEDATAGLTHMMIWHSNLNDATYQRTRALVRTGMDPRMCSLMQGS
TLPRRSGAAGAAIKGVGTMVMELIRMIKRGINDRNFWRGENGRRTRIAYERMCNILKG
KFQTAAQKAMMDQVRESRNPGNAEIEDLIFLARSALILRGSIAHKSCLPACVYGLAVAS
GYDFEREGYSLVGIDPFRLLQNSQVFSLIRPNENPAHKSQLVWMACHSAAFEDLRVSSFI
RGTRVIPRGQLSTRGVQIASNENVEAMDSSTLELRSRYWAIRTRSGGNTNQQRASAGQIS
VQPTFSVQRNLPFERATIMAAFKGNTEGRTSDMRTEIIRMMESARPEDVSFQGRGVFELS
DEKATNPIVPSFDMSNEGSYFFGDNAEEYDN

Indonesia

QDQICIGYHANNSTEQVDTIMEKNVTVTHAQDILEKTHNGKLCDLDGVKPLILRDCSVA
GWLLGNPMCDEFINVPEWSYIVEKANPTNDLCYPGSFNDYEELKHLLSRINHFEKIQIIPK
SSWSDHEASSGVSSACPYLGSPSFFRNVVWLIKKNSTYPTIKKSYNNTNQEDLLVLWGIH
HPNDAAEQTRLYQNPTTYISIGTSTLNQRLVPKIATRSKVNGQSGRMEFFWTILKPNDAI
NFESNGNFIAPEYAYKIVKKGDSAIMKSELEYGNCNTKCQTPMGAINSSMPFHNIHPLTI
GECPKYVKSNRLVLATGLRNS

H5N2 (Taiwan)
The amino acid sequence of H5N2 nucleoprotein is:
MLLVNQSHQGFNKEHTSKMVSAIVLYVLLAAAAHSAFASAGDRICIGYHANNSTTQVD
TIMEKNVTVTHAQDILEKEHNGRLCSLKGVKPLILKNCSVAGWLLGNPMCDEFLNAPE
WSYIVEKDRPSNGLCYPGTFNYYEELKHLMSSTNQFEKIQIFPRSSWSNHDASSGVSSAC
PYNGRSSFFRNVVWLIKKNNVYRTITRTYNNTNIEDLLIIWGIHHPNNAAEQIKLYQNPS
TYVSVGTSTLNQRSIPEIATRPKVNGLSGRMEFFWTILRPNDSITFESTGNFIAPEYAYKIV
KKGDSAIMKSELSYSNCDTKCQTPVGAINSSMPFHNVHPFAIGECPKYVKLKKLVLATG
LRNIPQRETRGLFGAIAGFIEGGWQGMVDGWYGYHHSNEQGSGYAADKESTQKAVDGI
TNKVNSIISKMNSQFEAVGKEFNNLERRIENLNKKMEDGFIDVWTYNAELLVLMENERT
LDLHDSNVKNLYDKVRRQLRDNAKELGNGCFEFYHRCDNKCMESVRNGTYDYPQYSE
ESRLKREEIDSGLVPRGSPGSGYIPEAPRDGQAYVRKDGEWVLLSTFLGHHHHHH

H5N8 (Washington)
The amino acid sequence of H5N8 nucleoprotein is:
GSGDSGSPGGTYINNTEPICDVKGFAPFSKDNGIRVGSRGHIFVIREPFVSCSPVGCRTFFL
TQGSLLNDKHSNGTVKDRSPFRTLMSVEVGQSPNVYQARFEAVAWSATACHDGKKW
MAIGVTGPDSKAVAVVHYGGVPTDVVNSWAGDILRTQESSCTCIQGNCYWVMTDGPA
NRQAQYRIYKANQGKIIGRKDVSFSGGHIEECSCYPNDGKVECVCRDNWTGTNRPVLIIS
PDLSYRVGYLCAGLPSDTPRGEDTQFVGSCTSPMGNQGYGVKGFGFRQGTDVWVGRTI
SRTSRSGFEIIRIKNGWTQTSKEQIRRQVVVDNSNWSGYSGSFTLPVELSGRECLVPCFW
VEMIRGRPEERTIWTSSSSIVMCGVDYEIADWSWHDGAILPFDIDKM

Development Plan

The cost mRNA is:

We will need 20 mg each of at least three proteins.

The cost stable formulation is about $100,000

The cost of first stage efficacy is about $100,000
The cost of early stage toxicology is about $50,000
Since the vaccine is intended for poultry, once we have efficacy proof and overall safety proof,
we can start testing it in a forced infection study where about 50 birds in each group are infected
and data compared within days of the incidence of infection, one week after administration of
vaccine.

Once proven, the technology will be transferred to Pakistan for local production and presented to
USDA to inquire about the additional cost for testing leading to a point of approval in poultry.
FDA does not regulate vaccines for animal diseases, these are regulated by the U.S. Department
of Agriculture. The bar for approval is lower than human vaccines.

Supply Chain
We will either license the technology or manufacture the vaccine under a contract through a
CMO and supply worldwide.

ROI
We intend to complete the vaccine technology within 24 months; Pakistan will receive royalty-
free turnkey technology and the investors will share 49% of all future revenues. The total
investment is expected to not exceed $2 Million. A detailed breakdown and timeline is available.
The investment will be returned by first paying out dividends to the investors.