Egg-Based Flu Vaccines
The most common way that flu vaccines are made is using an egg-based manufacturing process
that has been used for more than 70 years. Egg-based vaccine manufacturing is used to make both inactivated (killed) vaccine (usually called the “flu shot”) and live attenuated (weakened) vaccine (usually called the “nasal spray flu vaccine”).
The egg-based production process begins with CDC or another laboratory partner in the WHO Global Influenza Surveillance and Response System providing private sector manufacturers with candidate vaccine viruses (CVVs) grown in eggs per current FDA regulatory requirements. These CVVs are then injected into fertilized hen’s eggs and incubated for several days to allow the viruses to replicate. The fluid containing virus is harvested from the eggs. For inactivated influenza vaccines (i.e., flu shots), the vaccine viruses are then inactivated (killed), and the virus antigen is purified. The manufacturing process continues with quality testing, filling and distribution. For the nasal spray flu vaccine (i.e., the live attenuated influenza vaccine – LAIV), the starting CVVs are live, but weakened viruses that go through a different production process. FDA tests and approves all influenza vaccines prior to release and shipment.
There are several different manufacturers that use this production technology to make flu vaccines for use in the United States. This production method requires large numbers of chicken eggs to produce vaccine and may take longer than other production methods.
More about Egg-Based Flu Vaccines: https://en.wikipedia.org/wiki/Influenza_vaccine
Cell-Based Flu Vaccines
There also is a cell-based production process for flu vaccines that was approved by FDA in 2012. Until recently, this production process also began with egg-grown CVVs per FDA regulations. However, on August 31, 2016, FDA issued an approval for Seqirus, the sole FDA-approved cell-based flu vaccine manufacturer in the United States, to begin using cell-grown CVVs. Cell-based manufacturing is used to make inactivated flu vaccines (e.g., the flu shot).
The process of creating cell-based flu vaccines involves several steps. First, CDC or one of its laboratory partners, use influenza viruses that have been grown in cells to make CVVs, which are then provided to a vaccine manufacturer. Next, the vaccine manufacturer inoculates the CVVs into cultured mammalian cells (instead of into eggs) and allows the CVVs to replicate (i.e., make copies) for a few days. Then, the virus-containing fluid is collected from the cells and the virus antigen is purified. The manufacturing process continues with purification and testing. Finally, FDA tests and approves the vaccines prior to release and shipment.
Cell-based flu vaccine production does not require chicken eggs because the vaccine viruses used to make vaccine are grown in animal cells. Cell-based technology also has the potential for a faster start-up of the flu vaccine manufacturing process.
While viruses used in previous seasons’ cell-based vaccine have been grown in cells, prior to the 2019-2020 season some of the viruses provided to the manufacturer had been originally derived in eggs. For the 2019-2020 influenza season, all four flu viruses used in the cell-based vaccine are cell-derived, making the vaccine egg-free.
More about Cell-Based Flu Vaccines: https://en.wikipedia.org/wiki/Cell-based_vaccine
Recombinant Flu Vaccines
There is a third production technology for flu vaccines that was approved for use in the U.S. market in 2013 and that involves using recombinant technologyexternal icon. Recombinant flu vaccines do not require having a candidate vaccine virus (CVV) sample to produce. Instead, recombinant vaccines are created synthetically. To make a recombinant vaccine, flu scientists first obtain DNA, i.e., genetic instructions, for making a surface protein called hemagglutinin (HA) found on influenza viruses. HA is an antigen, which is a feature of a flu virus that triggers the human immune system to create antibodies that specifically target the virus. This DNA for making flu virus HA antigen is then combined with a baculovirus, a virus that infects invertebrates. This results in a “recombinant” virus. The role of the baculovirus is to help transport the DNA instructions for making flu virus HA antigen into a host cell. Once the recombinant virus enters a Food and Drug Administration (FDA) qualified host cell line, it instructs the cells to rapidly produce the HA antigen. This antigen is grown in bulk, collected, purified, and then packaged as recombinant flu vaccine. These vaccines are then quality and potency tested by FDA prior to FDA approving release of the vaccine lots to the public.
This production method does not require an egg-grown vaccine virus and does not use chicken eggs at all in the production process. While there are other vaccines on the U.S. market that use similar recombinant manufacturing processes, there is only one influenza vaccine produced using recombinant technology approved by the FDA for use in the United States at this time. This production process is the fastest because it is not limited by the selection of vaccine viruses that are adapted for growth in eggs or the development of cell-based vaccine viruses.
CDC and FDA monitor the safety of all vaccines licensed in the United States, including seasonal influenza vaccines.
More about Recombinant Flu Vaccines: https://en.wikipedia.org/wiki/Reverse_genetics
Cjepiva protiv gripe na bazi jaja
Najčešći način izrade cjepiva protiv gripe je postupak proizvodnje na bazi jaja
koja se koristi više od 70 godina. Proizvodnja cjepiva na bazi jaja koristi se za izradu i inaktiviranog (ubijenog) cjepiva (obično nazvanog „vakcina protiv gripe“) i živog oslabljenog (oslabljenog) cjepiva (obično nazvanog „nazalno cjepivo protiv gripe“).
Postupak proizvodnje zasnovan na jajima započinje s CDC-om ili drugim laboratorijskim partnerom u Svjetskom sustavu za nadzor i reagiranje na gripu, koji pruža proizvođačima iz privatnog sektora potencijalne viruse cjepiva (CVV) uzgojene u jajima prema trenutnim regulatornim zahtjevima FDA. Zatim se ti CVV ubrizgavaju u oplođena kokošja jaja i inkubiraju nekoliko dana kako bi se virusi mogli replicirati. Tekućina koja sadrži virus sakuplja se iz jajašaca. Za inaktivirana cjepiva protiv gripe (tj. Vakcine protiv gripe) virusi cjepiva se zatim inaktiviraju (ubijaju), a antigen virusa pročišćava. Postupak proizvodnje nastavlja se ispitivanjem kvalitete, punjenjem i distribucijom. Za cjepivo protiv gripe za nos (tj. Živo oslabljeno cjepivo protiv gripe - LAIV), početni CVV su živi, ali oslabljeni virusi koji prolaze kroz drugačiji proces proizvodnje. FDA testira i odobrava sva cjepiva protiv gripe prije puštanja i otpreme.
Postoji nekoliko različitih proizvođača koji koriste ovu tehnologiju proizvodnje za izradu cjepiva protiv gripe za upotrebu u Sjedinjenim Državama. Ova metoda proizvodnje zahtijeva velik broj kokošjih jaja za proizvodnju cjepiva i može potrajati dulje od ostalih metoda proizvodnje.
Cjepiva protiv gripe na bazi stanica
Također postoji postupak proizvodnje cjepiva protiv gripe zasnovan na stanicama, koji je FDA odobrila 2012. Donedavno je ovaj proizvodni postupak također započeo s CVV-ovima uzgojenim u jajima prema FDA propisima. Međutim, 31. kolovoza 2016. FDA je izdala odobrenje za Seqirus, jedini proizvođač cjepiva protiv gripe utemeljen na FDA-i u Sjedinjenim Državama, koji započinje s korištenjem staničnih CVV-a. Proizvodnja na bazi stanica koristi se za izradu inaktiviranih cjepiva protiv gripe (npr. Vakcina protiv gripe).
Proces stvaranja cjepiva protiv gripe na stanicama uključuje nekoliko koraka. Prvo, CDC ili jedan od njegovih laboratorijskih partnera, koriste viruse gripe koji su uzgojeni u stanicama za stvaranje CVV-a, koji se potom dostavljaju proizvođaču cjepiva. Dalje, proizvođač cjepiva inokulira CVV u kultivirane stanice sisavaca (umjesto u jaja) i omogućava CVV-ima da se repliciraju (tj. Prave kopije) nekoliko dana. Zatim se iz stanica sakuplja tekućina koja sadrži virus i pročišćava antigen virusa. Postupak proizvodnje nastavlja se pročišćavanjem i ispitivanjem. Konačno, FDA testira i odobrava cjepiva prije puštanja i otpreme.
Za proizvodnju cjepiva protiv gripe na bazi stanica nisu potrebna pileća jaja, jer se virusi cjepiva koji se koriste za izradu cjepiva uzgajaju u životinjskim stanicama. Stanična tehnologija također ima potencijal za brže pokretanje procesa proizvodnje cjepiva protiv gripe.
Iako su virusi korišteni u cjepivima na staničnoj osnovi u prethodnim sezonama uzgajani u stanicama, prije sezone 2019. - 2020. neki od virusa dostavljenih proizvođaču izvorno su nastali u jajima. Za sezonu gripe 2019.-2020., Sva četiri virusa gripe koja se koriste u cjepivu na staničnoj osnovi potječu od stanica, što cjepivo čini bez jajašaca.
Rekombinantna cjepiva protiv gripe
Postoji treća tehnologija proizvodnje cjepiva protiv gripe koja je odobrena za uporabu na američkom tržištu 2013. godine i koja uključuje upotrebu vanjske ikone rekombinantne tehnologije. Rekombinantna cjepiva protiv gripe ne trebaju imati uzorak kandidata za cjepivo protiv virusa (CVV) za proizvodnju. Umjesto toga, rekombinantna cjepiva stvaraju se sintetički. Da bi napravili rekombinantno cjepivo, znanstvenici gripe prvo pribavljaju DNK, tj. Genetske upute, za proizvodnju površinskog proteina nazvanog hemaglutinin (HA) koji se nalazi na virusima gripe. HA je antigen, što je značajka virusa gripe koja pokreće ljudski imunološki sustav da stvori antitijela koja ciljaju virus. Ova DNA za stvaranje HA antigena virusa gripe kombinira se s bakulovirusom, virusom koji inficira beskičmenjake. To rezultira „rekombinantnim“ virusom. Uloga bakulovirusa je pomoći u transportu DNA uputa za stvaranje HA antigena virusa gripe u stanicu domaćina. Jednom kada rekombinantni virus uđe u staničnu liniju domaćina koja je nadležna za hranu i lijekove (FDA), on upućuje stanice na brzu proizvodnju HA antigena. Ovaj se antigen uzgaja u rinfuzi, sakuplja, pročišćava i zatim pakira kao rekombinantno cjepivo protiv gripe. Zatim FDA testira kvalitetu i snagu prije nego što FDA odobri puštanje cjepiva u javnost.
Ova metoda proizvodnje ne zahtijeva virus cjepiva uzgojenog u jajima i uopće ne koristi kokošja jaja u proizvodnom procesu. Iako na američkom tržištu postoje druga cjepiva koja koriste slične rekombinantne proizvodne procese, postoji samo jedno cjepivo protiv gripe proizvedeno rekombinantnom tehnologijom koje je FDA odobrila za uporabu u Sjedinjenim Državama u ovom trenutku. Ovaj postupak proizvodnje je najbrži jer nije ograničen odabirom cjepiva virusa koji su prilagođeni rastu u jajima ili razvoju cjepivnih virusa na staničnoj osnovi.
CDC i FDA nadziru sigurnost svih cjepiva licenciranih u Sjedinjenim Državama, uključujući sezonska cjepiva protiv gripe.
