Vaccines and vaccination: history and emerging issues

Figures & data

Table 1. Vaccine immunization programs*

	Age	Disease	Vaccine brand/Manufacturer**	Vaccine type**
Childhood	Birth	Hepatitis B	H-B-Vax® II Paediatric/or Engerix B® Paediatric/GlaxoSmithKline	Recombinant vaccines, single dose vial or prefilled syringe, aluminum hydroxide adjuvant
	2 Months	Diphtheria, tetanus, pertussis, hepatitis B, polio, Haemophilus influenzae type b Pneumococcal Rotavirus	Infanrix® hexa/GlaxoSmithKline Prevenar 13/20®/Pfizer Rotarix®/GlaxoSmithKline or RotaTeq®/Merck Sharp & Dohme	Combination toxoid vaccine, aluminum hydroxide adjuvant Conjugate vaccine, diphtheriae CRM197 protein, aluminum phosphate adjuvant Live attenuated virus
	4 Months	Diphtheria, tetanus, pertussis, hepatitis B, polio, Haemophilus influenzae type b Pneumococcal Rotavirus	Infanrix® hexa/GlaxoSmithKline Prevenar 13/20®/Pfizer Rotarix®/GlaxoSmithKline or RotaTeq®/Merck Sharp & Dohme	As above As above As above
	6 Months	Diphtheria, tetanus, pertussis, hepatitis B, polio, Haemophilus influenzae type b	Infanrix® hexa/GlaxoSmithKline\ RotaTeq®/Merck Sharp & Dohme	As above
	12 Months	Meningococcal ACWY Pneumococcal Measles, mumps, rubella	Nimenrix®/Pfizer Prevenar 13/20®/Pfizer M-M-R® II/Merck Sharp & Dohme or Priorix®/GlaxoSmithKline	Conjugate tetanus toxoid, lyophilized As above Combination, live attenuated vaccines
	18 Months	Haemophilus influenzae type b Measles, mumps, rubella, varicella Diphtheria, tetanus, pertussis	Act-HIB®/Sanofi-Aventis Priorix-Tetra®/GlaxoSmithKline or ProQuad®/Merck Sharp & Dohme Infanrix®/GlaxoSmithKline or Tripacel®/Sanofi-Aventis	Conjugate tetanus protein (PRP-T) vaccine, lyophilized Combination live/ attenuated, lyophilized vaccines Combination toxoid vaccines, aluminum hydroxide/phosphate adjuvant
	4 Years	Diphtheria, tetanus, pertussis, polio	Infanrix® IPV/GlaxoSmithKline Quadracel®/Sanofi Pasteur	Combination toxoid and inactivated poliovirus, aluminum hydroxide adjuvant Combination toxoid and inactivated poliovirus, aluminum phosphate adjuvant
Adolescent	7 Years	Human papillomavirus (HPV) Diphtheria, tetanus, pertussis	Gardasil® 9/Merck Sharp & Dohme Boostrix®/GlaxoSmithKline	HPV, recombinant VLP vaccine, aluminum hydroxyphosphate sulfate adjuvant Combination toxoid vaccine aluminum, hydroxide and aluminum phosphate adjuvants
	12–13 Years	Human papillomavirus (HPV) Diphtheria, tetanus, pertussis	Gardasil® 9/Merck Sharp & Dohme Boostrix®/GlaxoSmithKline	As above As above
	14–16 Years	Meningococcal ACWY Meningococcal B vaccines	Nimenrix®/Pfizer Trumenba®/Pfizer	As above
Adult	15–49 Years	Pneumococcal	Pneumovax® 23/Merck Sharp & Dohme	Pneumococcal conjugated polysaccharide vaccine
	50 Years and over	Pneumococcal Shingles (herpes zoster)	Pneumovax® 23/Merck Sharp & Dohme Shingrix®/GlaxoSmithKline	As above
	65 Years and over	Pneumococcal	Pneumovax® 23/Merck Sharp & Dohme	As above
	70–79 Years	Shingles (herpes zoster)	Zostavax®/Merck Sharp & Dohme or Shingrix®	Zoster live/attenuated virus vaccine, lyophilized
	Pregnant women	Pertussis Influenza	Boostrix®/GlaxoSmithKline Adacel®/Sanofi-Aventis (2)Fluvax® CSL (5 years)/CSL Ltd (2)Agrippal®/Seqirus Vaccines Ltd (2)Fluarix®/GlaxoSmithKline (2)Influvac®/Mylan Health (2)Vaxigrip®/Sanofi-Pasteur	Boostrix®: As above Adacel®: Combination toxoid, aluminum phosphate adjuvant Others: Inactivated split virus
Other Vaccines	6 Months and over	Influenza	Fluvax® CSL (5 years)/CSL Ltd Agrippal®/Seqirus Vaccines Ltd Fluarix®/GlaxoSmithKline Influvac®/Mylan Health Vaxigrip®/Sanofi-Pasteur	All of them as above
	No age limit	Rabies	Merieux Inactivated Rabies Vaccine/Sanofi-Aventis Rabipur® inactivated Rabies virus vaccine/GlaxoSmithKline	Inactivated rabies virus grown in human diploid cells, lyophilized Inactivated rabies virus grown in purified chick embryo cells, lyophilized
	2 Months and over	Japanese encephalitis	JEspect®/Seqirus Imojev® (1 year)/Sanofi-Aventis	Inactivated virus, single dose prefilled syringe, aluminum hydroxide adjuvant Live attenuated virus, lyophilized
	9 Months and over	Yellow fever	Stamaril®/Sanofi-Aventis	Live attenuated virus, lyophilized

*This is not an exhaustive list. Adapted from the National Immunization Program Schedule of Australia, NWS Immunization Schedule and WHO.^28–32 Many other countries (like the US, UK) have specific lists to suit the vaccination programs in their individual countries.

**Vaccine brands are for Australia only; these may differ in other countries. Adapted from the Australian Immunization Handbook and NPS MedicineWise.^33,34

Figure 1. Different types/classes of vaccines. Vaccines are produced using different processes. Vaccines may contain live attenuated pathogens (usually viruses), inactivated whole pathogens, toxoids (an inactivated form of the toxin produced by bacteria that causes the disease), or parts of pathogens (e.g., natural or recombinant proteins, polysaccharides, conjugated polysaccharide or virus-like particles). Adapted from.³⁵

Figure 2. A highly simplified representation of the SARS-CoV-2 cell cycle. (A1) Virus entry generally occurs via surface glycoprotein (Spike protein, S-protein) binding to ACE2 receptor, TMPRSS2 also has a critical role to play in this process. Detailed interactions between S protein–ACE2 are also shown (courtesy of Dr. Serdar Kuyucak, USyd (A2). The virus can also enter by endocytosis (B&C). Subsequently, uncoating of viral proteins, primary translation, polyprotein processing and transcription take place. (D). Translation and viral RNA synthesis then occur (E). Other key steps such as accessory protein-host interactions take place prior to assembly and viral maturation. (F). Finally, release of mature viruses occurs via endocytosis.

Table 2. Major approved COVID-19 vaccines for emergency use^†

Type	Company	Country	Price/dose (US$)*	Efficacy (%)*	Dosage recommendation	Approval^#	Storage conditions	Common/Rare side effects**
mRNA	BioNtech Pfizer	Germany USA	19.5	95	2 doses, 3 weeks apart for 12 years and older (as of May 2021)	US, EU, UK, Turkey, Australia, Japan	Up to 6 months at −80 to −60°C Up to 5 days at 2–8°C	Common: Chills, headache, tiredness, and injection site adverse events (swelling, pain, redness) Rare: Can trigger anaphylaxis
	Moderna	USA	25–37	95	2 doses, 4 weeks apart for 18 years and older (other ages are being considered as of May 2021)	US, EU	Up to 6 months at −25 to −15°C Up to 30 days at 2–8°C	Common: As above Rare: As above
Viral Vector-based	AstraZeneca/ Oxford University	UK	2.15–5.25	~70	2 doses, 4–12 weeks apart for 18 years and older	EU, UK, Australia, India	Up to 6 months at 2–8°C	Common: As above Rare: Blood clots
	Johnson & Johnson	USA Belgium	10	66–72	1 dose for 18 years and older (under study for <18)	USA	Up to 3 months at 2–8°C	Common: As above (but less severe) Rare: Blood clots
	Sputnik V (Gamalaya Institute)	Russia	10	91.4	2	Russia, India, Turkey, Iran, Argentina (>60 countries)	−18°C (liquid form) 2–8°C (dry powder)	Common: As above and flu-like symptoms, fatigue Rare: Unknown
Inactivated Virus	CoronaVac^TM (Sinovac)	China	40–60	50–91	2	China, UAE, Indonesia, Turkey, Brazil	2–8°C	Common: As above, allergic reaction, cough, fever Rare: Unknown
	Sinopharm	China	18–40		2	China, Hungary, Venezuela, Sri Lanka (>40 countries)	2–8°C	Common: As above, fatigue Rare: Nausea and acute disseminated encephalomyelitis
	Covaxin® (Bharat Biotech)	India			2	India	2–8°C	Common: As above, fatigue, fever Rare: Unknown
Protein-based	Novavax	USA	16	89.3	2 doses, 3 weeks apart, being tested for adults 18–84 ages	Undergoing evaluation (Australia, EU, US, and others)	Up to 3 months at 2–8°C	Common: As above, fatigue, myalgia Rare: Unknown

^†Approvals in most countries are for Emergency Use only.

*Adapted from.^71,72

**Adapted from.^73–75

^#Not an exhaustive list of countries.

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