Traditional methods of vaccine production
The first human vaccines against viruses were based using weaker or attenuated viruses to generate immunity. The smallpox vaccine used cowpox, a poxvirus that was similar enough to smallpox to protect against it but usually didn’t cause serious illness. Rabies was the first virus attenuated in a lab to create a vaccine for humans.
Egg-Based Vaccines
Over the last 60 years, seasonal flu vaccines have been manufactured using fertilized embryonic eggs. Using this method, it takes about four months to produce a batch of vaccines for a new strain of influenza virus; from the moment the new influenza virus’ culture becomes available for vaccine manufacturing. The advantages of using embryonic eggs to manufacture seasonal flu vaccines are that the safety and effectiveness of the vaccines produced have been well established.
Cell-Based Vaccines
Since the mid 1990’s, newer vaccine manufacturing methods were developed. The cell-based vaccine manufacturing process is one of such methods. The cell-based vaccine manufacturing process uses cells from mammals to culture the influenza virus for vaccine production. Various pharmaceutical companies use different sources of mammalian cell cultures for the vaccine manufacturing process. Baxter Healthcare uses cells extracted from the kidney of the African Green Monkey while companies such as Solvay Biologicals and Novartis Vaccines use kidney cells from canines to produce seasonal flu vaccines.
Production of DPT vaccine
DPT is a class of combination vaccines against three infectious diseases in humans: diphtheria, pertussis (whooping cough), and tetanus. The vaccine components include diphtheria and tetanus toxoids and killed whole cells of the bacterium that causes pertussis.
Although different combinations may contain the same toxoids or antigens each vaccine may differ substantially according to the toxoid or antigen dose, number of pertussis components (for acellular vaccines), method of purification and inactivation of the toxins and incorporation of adjuvants and excipients. All of these factors may have an impact on the reactogenicity of different DTP vaccine combinations.
Diphtheria and Tetanus (DT and Td) toxoid combination: DT vaccine used for primary immunisation and boosting in children contains 6.7-25Lf of diphtheria toxoid and 5 – 7.5 Lf of tetanus toxoid per dose. An adult combination, Td, is used for boosting and primary immunisation in adolescents and adults and contains a lower dose of diphtheria (less than 2 Lf/dose) but a similar dose of tetanus toxoid.
Diphtheria, Tetanus and Pertussis (DTP) combinations: Initial DTP combination preparations contained whole-cell pertussis antigens. Concern due to common occurrence of minor local reactions and less common severe reactions of whole-cell pertussis led to the development of acellular vaccines and clinical trials demonstrating their efficacy in the 1980’s. Multiple acellular pertussis vaccines are now available and are referred to by the number of acellular antigen components that they contain. Whole-cell pertussis vaccine remains a safe, inexpensive and effective vaccine which is used in many countries because whole cell vaccines that generate a higher level of antibody to pertussis toxin are associated with higher vaccine efficacy.
DTP with other vaccine antigen combinations: There are many vaccine formulations containing diphtheria and tetanus toxoids and whole cell or acellular pertussis antigens in combination with Haemophilus influenzae type b, hepatitis B and/or inactivated polio virus to produce quadrivalent, pentavalent and hexavalent combination vaccines.
Rabies vaccine
Pre-exposure vaccination should be offered to people at high risk of exposure to rabies, such as laboratory staff working with rabies virus, veterinarians, animal handlers and wildlife officers, and other individuals living in or travelling to countries or areas at risk. Travellers with extensive outdoor exposure in rural areas – such as might occur while running, bicycling, hiking, camping, backpacking, etc. – may be at risk, even if the duration of travel is short. Preexposure vaccination is advisable for children living in or visiting countries or areas at risk, where they provide an easy target for rabid animals. Pre-exposure vaccination is also recommended for individuals travelling to isolated areas or to areas where immediate access to appropriate medical care is limited or to countries where modern rabies vaccines are in short supply and locally available rabies vaccines might be unsafe and/or ineffective.
Pre-exposure rabies vaccination consists of three full intramuscular (i.m.) doses of cell-culture- or embryonated-egg-based vaccine given on days 0, 7 and 21 or 28 (a few days’ variation in the timing is not important). For adults, the vaccine should always be administered in the deltoid area of the arm; for young children (under 1 year of age), the anterolateral area of the thigh is recommended. Rabies vaccine should never be administered in the gluteal area: administration in this manner will result in lower neutralizing antibody titres.
To reduce the cost of cell-derived vaccines for pre-exposure rabies vaccination, intradermal (i.d.) vaccination in 0.1-ml volumes on days 0, 7 and either 21 or 28 may be considered. This method of administration is an acceptable alternative to the standard intramuscular administration, but it is technically more demanding and requires appropriate staff training and qualified medical supervision. Concurrent use of chloroquine can reduce the antibody response to intradermal application of cell-culture rabies vaccines. People who are currently receiving malaria prophylaxis or who are unable to complete the entire three-dose pre-exposure series before starting malarial prophylaxis should therefore receive pre-exposure vaccination by the intramuscular route.
Periodic booster injections are not recommended for general travellers. However, in the event of exposure through the bite or scratch of an animal known or suspected to be rabid, individuals who have previously received a complete series of pre- or post-exposure rabies vaccine (with cell-culture or embryonated-egg vaccine) should receive two booster doses of vaccine. Ideally, the first dose should be administered on the day of exposure and the second 3 days later. This should be combined with thorough wound treatment (see “Post-exposure prophylaxis”, below). Rabies immunoglobulin is not required for patients who have previously received a complete vaccination series.