The Pros and Cons of Different COVID Vaccine Technologies Explained

 In COVID-19

The World Health Organisation lists about 180 COVID-19 vaccines being devel­oped around the world.

Each vac­cine aims to use a slight­ly dif­fer­ent approach to pre­pare your immune system to recog­nise and fight SARS-CoV‑2, the virus that causes COVID-19.

However, we can group these tech­nolo­gies into five main types. Some tech­nol­o­gy is tried and trust­ed. Some tech­nol­o­gy has never before been used in a com­mer­cial vac­cine for humans.

As we out­line in our recent paper, each tech­nol­o­gy has its pros and cons.

1. DNA/RNA-based

DNA and RNA vac­cines use frag­ments of genet­ic mate­r­i­al made in the lab. These frag­ments code for a part of the virus (such as its spike protein). After the vac­cine is inject­ed, your body uses instruc­tions in the DNA/RNA to make copies of this virus part (or anti­gen). Your body recog­nis­es these and mounts an immune response, ready to pro­tect you the next time you encounter the virus.


  • these vac­cines can be quick­ly designed based on genet­ic sequenc­ing alone

  • they can be easily man­u­fac­tured, mean­ing they can poten­tial­ly be pro­duced cheap­ly

  • the DNA/RNA frag­ments do not cause COVID-19.


  • there are no approved DNA/RNA vac­cines for med­ical use in humans, hence their alter­na­tive name: next-gen­er­a­tion vac­cines. So they are likely to face con­sid­er­able reg­u­la­to­ry hur­dles before being approved for use

  • as they only allow a frag­ment of the virus to be made, they may prompt a poor pro­tec­tive immune response, mean­ing mul­ti­ple boost­ers may be needed

  • there’s a the­o­ret­i­cal prob­a­bil­i­ty vac­cine DNA can inte­grate into your genome.

The speed at which these vac­cines can be designed, need­ing only the genet­ic sequence of the virus, is why these vac­cines were among the first to enter clin­i­cal trials.

An RNA vac­cine, mRNA-1273, being devel­oped by Moderna and the US National Institute of Allergy and Infectious Diseases, advanced to clin­i­cal test­ing just two months after the virus was sequenced.

2. Virus vec­tors

These vac­cines use a virus, often weak­ened and inca­pable of caus­ing dis­ease itself, to deliv­er a virus anti­gen into the body. The virus’ abil­i­ty to infect cells, express large amount of anti­gen and in turn trig­ger a strong immune response make these vac­cines promis­ing.

Examples of virus­es used as vec­tors include vaccinia virus (used in the first ever vac­cine, against small­pox) and adenovirus (a common cold virus).


  • highly spe­cif­ic deliv­ery of anti­gens to target cells and high expres­sion of anti­gen after vac­ci­na­tion

  • often a single dose is enough to stim­u­late long-term pro­tec­tion.


  • people may have exist­ing levels of immune pro­tec­tion to the virus vector, reduc­ing the effec­tive­ness of the vac­cine. In other words, the body raises an immune response to the vector rather than to the anti­gen

  • low-scale pro­duc­tion of some virus-vec­tored vac­cines means they are less cost-effec­tive.

One high-pro­file exam­ple is the University of Oxford/AstraZeneca vac­cine AZD1222 (for­mer­ly known as ChAdOx1), one of the two vac­cines the Australian gov­ern­ment wishes to use should phase 3 clin­i­cal trials prove suc­cess­ful. This vac­cine is based on a mod­i­fied chim­panzee ade­n­ovirus.

Read more: The Oxford deal is welcome, but remember the vaccine hasn't been proven to work yet

Two ade­n­ovirus based COVID-19 vac­cines have been approved for early or lim­it­ed use inter­na­tion­al­ly. These were devel­oped by the Chinese Academy of Military Medical Sciences with CanSino Biologics and the Gamaleya Research Institute, part of Russia’s health min­istry.

Read more: Russian coronavirus vaccine results have been published – here's what they reveal

3. Inactivated

Inactivated vac­cines are a tried and trust­ed method of vac­ci­na­tion. It’s the tech­nol­o­gy used in the vac­cine against poliovirus and in some types of flu vaccines. Inactivated vac­cines con­tain virus­es treat­ed with heat, chem­i­cals, or radi­a­tion so they cannot repli­cate, but can still trig­ger an immune response.



  • low immuno­genic­i­ty, so requires mul­ti­ple boost­ers.

The Chinese gov­ern­ment has grant­ed emergency approval for lim­it­ed use of an inac­ti­vat­ed COVID-19 vac­cine devel­oped by Sinovac Biotech.

4. Live-atten­u­at­ed virus

Live-attenuated vaccines are among the most suc­cess­ful exist­ing vac­cine strate­gies, already used to pro­tect against measles and polio. These con­tain virus weak­ened in the lab. The virus is still viable (live) but cannot cause dis­ease. After vac­ci­na­tion, the virus­es in these vac­cines grow and repli­cate, stim­u­lat­ing an excel­lent immune response.


  • strong pro­tec­tion as vac­cine mimics the nat­ur­al infec­tion process

  • cost effec­tive for large-scale man­u­fac­tur­ing with a famil­iar reg­u­la­to­ry approval path­way

  • single immu­ni­sa­tion with­out need­ing extra mol­e­cules (adju­vants) to stim­u­late the immune system.


  • very rare poten­tial to revert to a dis­ease-caus­ing state

  • lim­it­ed use in people with weak­ened immune sys­tems due to poten­tial safety con­cerns

  • can require cold stor­age, which may limit poten­tial for dis­tri­b­u­tion.

Several live-atten­u­at­ed COVID-19 vac­cine can­di­dates are cur­rent­ly in pre­clin­i­cal trials.

Our group, at Griffith University, has partnered with vac­cine man­u­fac­tur­er Indian Immunologicals Ltd to devel­op a live-atten­u­at­ed COVID-19 vac­cine.

Read more: Could BCG, a 100-year-old vaccine for tuberculosis, protect against coronavirus?

5. Protein sub­unit

Subunit vac­cines do not con­tain live com­po­nents of the virus, but are made from puri­fied pieces of the virus (pro­tein anti­gens) that trig­ger an immune response. Again, this is an exist­ing tech­nol­o­gy, used for instance in hepatitis B vac­cines.


  • with no live com­po­nents, sub­unit vac­cines are gen­er­al­ly thought to be safe

  • can be used in people with weak­ened immune sys­tems and other vul­ner­a­ble pop­u­la­tions.


  • the pro­tein anti­gens that best elicit an immune response must be inves­ti­gat­ed in detail

  • can stim­u­late an insuf­fi­cient immune response mean­ing that pro­tec­tion is likely to require mul­ti­ple boost­ers or for the vac­cine to be given with an immune system stim­u­lant.

The University of Queensland has developed a pro­tein sub­unit vac­cine for COVID-19 that is being com­bined with an immune stim­u­lant made by CSL. It is anoth­er one of the vac­cines Australia wishes to use, should phase 3 clin­i­cal trials prove suc­cess­ful.

Read more: Putting our money on two COVID vaccines is better than one: why Australia's latest vaccine deal makes sense

In a nut­shell

Not all vac­cines cur­rent­ly being devel­oped to pre­vent COVID-19 will be suc­cess­ful. Safety issues or a lack of pro­tec­tion will halt some.

So, a broad port­fo­lio of vac­cine approach­es and tech­nolo­gies is pro­gress­ing through human trials is reas­sur­ing. We don’t want to put all our eggs in one basket.

Ultimately, it is likely we’ll need a reper­toire of COVID-19 vac­cines to offer wide­spread pro­tec­tion. Different vac­cine for­mu­la­tions will ensure vac­ci­na­tion is safe and effec­tive for all mem­bers of soci­ety, includ­ing infants, the elder­ly and people with weak­ened immune sys­tems.

Read more: 5 ways our immune responses to COVID vaccines are unique

The Conversation

Suresh Mahalingam, Principal Research Leader, Emerging Viruses, Inflammation and Therapeutics Group, Menzies Health Institute Queensland, Griffith University and Adam Taylor, Early Career Research Leader, Emerging Viruses, Inflammation and Therapeutics Group, Menzies Health Institute Queensland, Griffith University

This arti­cle is repub­lished from The Conversation under a Creative Commons license. Read the original article.

Image: Reuters

National Interest source|articles

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