Antibody Response To Vaccine Does Not Equal Immunity or Protection
Posted by vaccinesme on Wednesday, January, 28 2009 and filed under Basics
Key topics: Antibodies Antibody

This is readily admitted in some papers - that antibodies do not equal immunity. We'll take a few quotes from some papers to give some examples. Before doing that though consider that vaccines are tested for effectiveness by measuring antibodies, even though this has never been proven to be a measure of immunity. We are told that if you raise antibodies you are protected, and thus vaccines that raise antibodies are characterized as being effective. This is what you find in the marketing of vaccines through the variety of channels, in leaflets, in media reports, from the medical profession and so on.

Del Giudice G, Podda A, Rappuoli R. IRIS Research Center, Chiron SpA, Via Fiorentina 1, 53100, Siena, Italy. What are the limits of adjuvanticity? Vaccine. 2001 Oct 15;20 Suppl 1:S38-41.

There are a lot of interesting points in this abstract, however for fear of digressing we won't address them here, but they relate to the way in which vaccines skew the immune system (leading to development of allergies and autoimmune responses). The relevant part to our discussion here though, has been bolded.

Vaccines developed traditionally following empirical approaches have often limited problems of immunogenicity, probably due to the low level of purity of the active component(s) they contain. The application of new technologies to vaccine development is leading to the production of purer (e.g. recombinant) antigens which, however, tend to have a poorer immunogenicity as compared to vaccines of the previous generation. The search for new vaccine adjuvants involves issues related to their potential limits. Since the introduction of aluminium salts as vaccine adjuvants more than 70 years ago, only one adjuvant has been licensed for human use. The development of some of these new vaccine adjuvants has been hampered by their inacceptable reactogenicity. In addition, some adjuvants work strongly with some antigens but not with others, thus, limiting their potentially widespread use. The need to deliver vaccines via alternative routes of administration (e.g. the mucosal routes) in order to enhance their efficacy and compliance has set new requirements in basic and applied research to evaluate their efficacy and safety. Cholera toxin (CT) and labile enterotoxin (LT) mutants given along with intranasal or oral vaccines are strong candidates as mucosal adjuvants. Their potential reactogenicity is still matter of discussions, although available data support the notion that the effects due to their binding to the cells and those due to the enzymatic activity can be kept separated. Finally, adjuvanticity is more often evaluated in terms of antigen-specific antibody titers induced after parenteral immunization. It is known that, in many instances, antigen-specific antibody titers do not correlate with protection. In addition, very little is known on parameters of cell-mediated immunity which could be considered as surrogates of protection. Tailoring of new adjuvants for the development of vaccines with improved immunogenicity/efficacy and reduced reactogenicity will represent one of the major challenges of the ongoing vaccine-oriented research.

Next a statement from an MMWR report (March 28, 1997 / 46(RR-7);1-25) regarding antibodies to pertussis (whooping cough):

The findings of efficacy studies have not demonstrated a direct correlation between antibody responses and protection against pertussis disease. However, antibody studies are useful to compare immune responses elicited by a single vaccine under different conditions or in different studies. Thus, efficacy studies are required to measure clinical protection conferred by each pertussis vaccine.

Next a study involving tetanus vaccination:

Crone NE, Reder AT. Department of Neurology, University of Chicago, IL 60637. Severe tetanus in immunized patients with high anti-tetanus titers. Neurology. 1992 Apr;42(4):761-4.

Severe (grade III) tetanus occurred in three immunized patients who had high serum levels of anti-tetanus antibody. The disease was fatal in one patient. One patient had been hyperimmunized to produce commercial tetanus immune globulin. Two patients had received immunizations 1 year before presentation. Anti-tetanus antibody titers on admission were 25 IU/ml to 0.15 IU/ml by hemagglutination and ELISA assays; greater than 0.01 IU/ml is considered protective. Even though one patient had seemingly adequate anti-tetanus titers by in vitro measurement (0.20 IU), in vivo mouse protection bioassays showed a titer less than 0.01 IU/ml, implying that there may have been a hole in her immune repertoire to tetanus neurotoxin but not to toxoid. This is the first report of grade III tetanus with protective levels of antibody in the United States. The diagnosis of tetanus, nevertheless, should not be discarded solely on the basis of seemingly protective anti-tetanus titers.

Meaning, that despite presence of antibodies in amounts greater than what is deemed sufficient for protection, diagnosis of tetanus should not be discarded. In other words, mere existence of antibodies does not protect from the disease.

Another tetanus example:

S.Y. Maselle, R. Matre, R. Mbise, T. Hofstad. Neonatal tetanus despite protective serum antitoxin concentration. FEMS Microbiology Letters, Volume 76 Issue 3, Pages 171 - 176. Federation of European Microbiological Societies.

Using the ELISA technique to estimate serum antibodies against tetanus toxin, seven neonates with clinical tetanus were found to have antibody levels 4-13 times higher than the presumed minimum protective level of 0.01 IU/ml All but one of their mothers had been vaccinated with tetanus toxoid in pregnancy. In two other neonates, whose mothers had received multiple booster doses of toxoid during pregnancy, the anti-toxin concentrations were 100- and 400-times the presumed protective level.

And in a Canada Communicable disease Report (Vol. 23 (ACS-3) 15 July 1997):

An Advisory Committee Statement (ACS)
National Advisory Committee on immunization (NACI)
STATEMENT ON pertussis vaccine

... There is no known direct correlation between levels of specific pertussis antibodies and protection against pertussis. For whole-cell pertussis vaccines, vaccine potency and efficacy correlate with a minimum of four international units (IUs) in the intracerebral mouse-protection assay. Susceptibility of a population to pertussis correlates best with agglutinin antibodies but these do not adequately predict protection in an individual...