Principle 3: A large challenge dose can overcome immunity
In some conditions, immunity can be overcome by large infectious doses.
Example: Vaccination against poliomyelitis is very effective in preventing paralysis due to the induction of serum antibody. However, gut (intestinal) immunity can be overcome by large infectious doses. A study recruited subjects who had previously received either live or killed vaccine. Participants were given two different doses of oral live vaccine- 800 or 600,000 TCID50 (median tissue culture infective dose). Those who had previously received live vaccine were infected by the low dose challenge 3% of the time and 15% of the time by the high-dose challenge. In contrast, 30% of those who previously received the killed vaccine were infected by a low dose and 70% by a high dose. This indicates that high infectious doses can overcome intestinal immunity.
Principle 4: Most current vaccines protect through antibodies
Except in the cases of zoster and tuberculosis, where stimulation of specific T-cell subsets correlates with protection, antibodies are the primary mechanism of protection.
Many viral and bacterial agents reach target organs through viraemia or bacteraemia. Therefore, antibodies can prevent their passage. Even when agents replicate only on the mucosa, the presence of local antibody is preventive. Toxin producing bacteria like tetanus can be restricted by antitoxic antibodies.