DETERMINANTS OF IMMUNE RESPONSE

Success of vaccination in an individual child is assessed by:

• Seroconversion, i.e. development of antibodies after administration of a vaccine or more than four-fold rise in pre-vaccination titers, if already present due to previous exposure.

• Seroprotection, i.e. development of antibodies in the pre-defined titers required for protection from the disease.

• Immunogenicity, i.e. ability of the vaccine to induce seroprotective titers or desired cell mediated response.

• Protective efficacy, i.e. ability of the vaccine to actually reduce the risk of disease in vaccinated population as compared to unvaccinated population, denoted in terms of percentage.

In brief, immunogenicity is a laboratory criteria to assess the effect of a vaccine, while protective efficacy is a real-life field result.

Important determinants of success after individual vaccination include:

• Type of the antigen: Live vaccines are highly immunogenic due to endogenous production of antigen due to in vitro multiplication of organisms, as compared to killed, subunit or toxoid vaccines that carry limited antigenic load per dose. Polysaccharide vaccines are poorly immunogenic as they produce only T-cell independent response of mainly IgM class with no development of memory cells, being gradually replaced by conjugated vaccines. Hence, while live vaccines are usually given as a single dose, inactivated vaccines, need multiple primary doses and boosters for adequate and sustained immune response.

• Number of doses: Increasing the number of doses increases immunogenicity and efficacy of a vaccine, specially in cases of inactivated vaccines. Immunocompromised child are often advised to take additional dose/s of these vaccines. While one dose is generally enough for most of live vaccines, additional dose are frequently advised to ensure better seroprotection, e.g.

• Dose of the antigen: Higher doses of antigen induce better immunity but with higher risk of side effects and hence, increasing the antigen content beyond a limit is not recommended. Still, higher (double dose) vaccinations are sometimes recommended in immunocompromised populations, e.g. for HBV vaccine.

• Immune status of host: Vaccination in preterms, malnourished and immunocompromised children may not produce adequate immune response due to relative immune incompetence. Although live vaccines may theoretically produce the disease in these cases, such complications are extremely rare and should not preclude the use of live vaccines except in severe immunodeficiency states.

• Time-interval between doses: A gap of less than one month between two doses of non-live vaccines may not produce adequate secondary response. Although an interval of two months produces best secondary response, need to complete the immunization as early as possible in the baby has necessitated use of one- month interval between two doses of DPT, etc.

• Time interval between different vaccines: When two live vaccines for different diseases are given at short interval (lt;1 months), early non-specific immune response to the previous vaccine may interfere with uptake of the subsequent vaccine. Hence, a minimum interval of one month is essential for adequate response to each live vaccine. However, multiple live vaccines, given on the same day produce parallel and adequate immune response for each of them and hence, use of combination vaccines is as effective as separate vaccinations.

No specific time-interval is needed between two inactivated vaccines or one-live and one inactivated vaccine,

barring few exceptions: (a) PCV should always precede PPSVby 8 weeks, when used together, and (b) PCVshould precede meningococcal vaccine by 4 weeks, when used together.

• Presence of maternal antibodies during first 3-6 months of life interferes with successful active immunization by rapid elimination of the vaccine­antigen.

Maternal antibodies interfere more with response to live vaccines than to inactivated vaccines. Hence, while inactivated vaccines, e.g. DPT, PCV can be given earlier at 6 weeks, live vaccines are usually not given before 9 months of age, e.g. MR or varicella.

• Route of administration: Parenteral vaccines mainly induce systemic immunity, while oral vaccines, e.g. OPV and Rotavirus vaccines mainly induce local immunity (secretory IgA-mediated). Local immunity prevents the invasion of pathogen itself, while systemic or IgG-mediated immunity eliminates the organism after invasion.

Intradermal vaccination of some vaccines, e.g. IPV or Rabies vaccines, can induce antibody responses comparable to intramuscular or subcutaneous route with lesser dose of antigen.

• Presence of pre-formed antibodies after immuno­globulin therapy or after blood transfusions interferes with development of adequate immune response by rapid elimination of vaccine-antigen. Hence, a gap of many weeks to months is usually recommended between administration of these products and vaccines. However, as immunological protection by vaccines is delayed by several days. Some immuno­globulins, e.g. tetanus, hepatitis B and rabies immunoglobulins are given along with the first dose of vaccine due to the urgency of protection before appearance of vaccine-induced response.

• Contact immunity and herd effect: Some vaccines benefit even the unvaccinated population, through various ways, i.e. Contact immunity (shedding of the OPV virus in stools or influenza virus in nasal secretions after respective vaccinations, unintentionally vaccinating the contacts) and Herd effect (reducing the transmission of disease by decreasing the number of susceptible population). In these cases, the actual protective efficacy of the vaccine might be higher than that expected from the vaccine.

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