Secondary measles vaccine failures identified by measurement of IgG avidity: high occurrence among teenagers vaccinated at a young age

Abstract

Failure to seroconvert (primary vaccine failure) is believed to be the principal reason (approx. > 95%) why some vaccinees remain susceptible to measles and is often attributed to the persistence of maternal antibodies in children vaccinated at a young age. Avidity testing is able to separate primary from secondary vaccine failures (waning and/or incomplete immunity), but has not been utilized in measles epidemiology. Low-avidity (LA) and high-avidity (HA) virus-specific IgG antibodies indicate primary and secondary failure, respectively. Measles vaccine failures (n = 142; mean age 10.1 years, range 2-22 years) from an outbreak in 1988-9 in Finland were tested for measles-virus IgG avidity using a protein denaturating EIA. Severity of measles was recorded in 89 failures and 169 non-vaccinees (mean age 16.2 years, range 2-22 years). The patients with HA antibodies (n = 28) tended to have clinically mild measles and rapid IgG response. Among failures vaccinated at < 12, 12-15 and > 15 months of age with single doses of Schwarz-strain vaccine in the 1970s, 50 (95% CI 1-99), 36 (CI 16-56) and 25% (CI 8-42) had HA antibodies, respectively. When a single measles, mumps and rubella (MMR) vaccine had been given after 1982 at 15 months of age, only 7% (CI 0-14) showed HA antibodies. Omitting re-vaccinees and those vaccinated at < 15 months, Schwarz-strain recipients had 3.6 (CI 1.1-11.5) higher occurrence of HA responses compared to MMR recipients. Apart from one municipality, where even re-vaccinees had high risk of primary infection, 89% (CI 69 to approximately 100) of the infected re-vaccinees had an HA response. Secondary measles-vaccine failures are more common than was more previously thought, particularly among individuals vaccinated in early life, long ago, and among re-vaccinees. Waning immunity even among individuals vaccinated after 15 months of age, without the boosting effect of natural infections should be considered a relevant possibility in future planning of vaccination against measles.

Reduced Ability of Neonatal and Early-Life Bone Marrow Stromal Cells to Support Plasmablast Survival

“…We currently do not know whether the limitations of the BM compartment reported in our early-life murine models affect human infants. However, the relative stability during several years of most Ag-specific serum IgG levels in adults is in striking contrast to their rapid decline when immunization is performed during the first year of life (13)(14)(15)(16). In addition, it is striking that the stage of immune maturation that is sufficient for the induction of strong short-lived Ab responses is reached in both species much earlier in life than the one associated with the induction of sustained Ab levels.…”

“…It is tempting to postulate that evolution could have resulted into a delayed development of plasma cell BM niches so as to preferentially support rapid changes in serum Ab profiles rather than the long-term persistence of Abs against neonatally encountered Ags. A delayed induction of functional BM niches would result in enhanced competition between plasmablasts elicited in response to early encountered Ags and thus play an important role in the shorter duration of early-life Ab response to infections and immunization (13)(14)(15)(16). This will need to be taken into careful consideration for the design of immunization program requiring the maintenance of sustained Ab responses following early-life immunization.…”

“…Importantly, it was recently recognized that the persistence of these Ab responses is much shorter than those elicited in older children or adults. Even when high Ab titers have eventually been generated through repeat infant immunization, serum Abs rapidly decline and disappear within a few months (13)(14)(15)(16)(17). This may be associated with a resurgence of vulnerability to infection (17,18), requiring the administration of vaccine boosters already in the second year of life.…”

Depletion of measles virus glycoprotein-specific antibodies from human sera reveals genotype-specific neutralizing antibodies

“…Primary and secondary vaccination failures have been associated with susceptibility et al, 1987;Fine & Zell, 1994;De Serres et al, 1995;Sutcliffe & Rea, 1996;Paunio et al, 2000), whereas naturally immune subjects only rarely become susceptible to subclinical MV reinfection (Muller et al, 1996). It has been speculated that susceptibility to reinfection could be facilitated by genetic differences between the MV vaccine virus and currently circulating wt MV strains (Tamin et al, 1994; Santibanez et al, 2005 Here, we have used the antibody depletion approach to study the relative contribution of H-and F-specific antibodies in sera from naturally immune subjects to VN activity against both MV Edmonston and wt MV.…”

An Agent-Based Model of School Closing in Under-Vacccinated Communities During Measles Outbreaks

“…MMR vaccinations may fail if the primary dose is given to infants protected by maternal antibodies transferred during breast-feeding [2]. Avidity testing can be used to assess the efficacy of vaccinations, but such tests are not widely utilized in measles epidemiology [32]. Thus, it can be misleading to take statistical data at face value regarding assumed levels of protection for given levels of a vaccination coverage [29].…”