Long‐lasting immunity by early infection of maternal‐antibody‐protected infants

Abstract

Newborn higher vertebrates are largely immuno-incompetent and generally survive infections -including poxviruses -by maternal antibody protection. Here, we show that mice survived epidemics as adults only if exposed to lethal orthopoxvirus infections during infancy under the umbrella of maternal protective antibodies. This implies that both the absence of exposure to infection during early infancy or of effective vaccination renders the population highly susceptible to new or old re-emerging pathogens.Key words: Ectromelia . Maternal antibody . Protection . Vaccination . Vaccinia IntroductionIn the last 50 years, several viral diseases have been largely confined or even eradicated, as in the case of smallpox (variola virus) for which routine vaccinations with vaccinia virus (VACV) have been subsequently stopped in the 1970s. Due to loss of regular exposure to immunizing viral antigens, herd immunity might wane and leave the population susceptible to pathogen reemergence. Therefore, the consequences of interruption of the natural re-exposure cycles in the absence of infectious antigen contact need to be better understood.For these studies, we used orthopoxvirus infections because in both humans and mice the species-specific pox virus has devastating consequences with mortalities reaching 50-80% in the 14th century in Europe or up to 100% for certain mouse colonies in research establishments. Newborn and infant mice are highly susceptible to WT of ectromelia (mousepox) virus (ECTV) and the empirically selected VACV [1][2][3]. Resistance to ECTV varies between mouse strains; C57BL/6 are one of the genetically more resistant strains. Orthopox viruses such as variola virus, VACV, and ECTV share the cross-reactive neutralizing protective epitope [4] in addition to many T-cell specificities. Accordingly, vaccination with VACV provides solid protection to smallpox or mousepox (named sometimes ''smallpox of mice'') [5,6]. In this paper, we describe that long-lasting immunological protection results after immuno-incompetent pups of immune mice encounter an otherwise lethal pox-virus infection. Results and discussionWe compared survival of Moscow strain of Ectromelia virus (ECTV-MOS) infection at the age of 12-42 wk when specific pathogen-free infant C57BL/6 (H-2 b ) mice from immune mothers had been exposed to a lethal orthopox virus infection within the first days of life or not. C57BL/6 dams were immunized with 2 Â 10 6 pfu of VACV WR (LD50$10 8 pfu). Four weeks later they were mated with normal male mice. The newborn pups were infected intranasally at day 1 of age with 3-10 LD 50 corresponding to about 10 3 pfu of VACV WR ( We do not define maternal antibodies as the sole effector mechanism in this study, although they are the only ones transferred from the mother to the offspring. The theoretical possibility that viral antigen persisting in the mother could have been transferred to immunize newborns is unlikely because first, mothers were vaccinated 4 wk before pregnancy and second, without challenge infection early a...

Early infections by myxoma virus of young rabbits (Oryctolagus cuniculus) protected by maternal antibodies activate their immune system and enhance herd immunity in wild populations

“…These observations show that, in the rabbit/myxomatosis system, maternal antibodies do not prevent rabbits from being infected but attenuate infection and do not prevent an immune response from infected juveniles. Our data therefore support Zinkernagel’s hypothesis in accordance with similar observations made on other host/parasite systems [17-20,23-25]. …”

“…In such endemic conditions, the disease has a low impact. In addition to the mechanisms described by Fouchet et al [9,11], one cannot rule out that long-term effects of maternal immunity [23-25] have contributed to establish a strong herd immunity and to reduce the impact of the disease in the two populations studied.…”

“…However, other studies have shown that, in cases of early infection, maternal antibodies can only reduce the severity of the disease, thereby enabling the host immune system to develop acquired immunity without the cost of a severe disease [17-20], as initially proposed by Zinkernagel [21,22]. Maternal immunity may also have long-term effects: even in the absence of early infection, individuals born with maternal antibodies may display an enhanced immune response when infection occurs after maternal immunity has waned [23-25]. In addition, maternal immunity may even have positive trans-generational effects on offspring of females having received maternal antibodies from their own mother [25].…”

Measles Vaccination in the Presence or Absence of Maternal Measles Antibody: Impact on Child Survival

“…First, it has been suggested from an early 2-dose study in Sudan that early MV in presence of maternal antibody may prime for a balanced humoral and cellular immune response to subsequent revaccination [27]. Animal studies have suggested that maternal antibody not only confers passive immunity, but also leaves a long-lasting imprint on the immune system of the offspring [28], and that presence of maternal antibody at primary infection is required to ensure long-term protection [29]. Second, maternal antibodies have undergone immune maturation due to somatic hypermutation and gene conversion and are thus guided toward the dominant epitopes on the measles virus.…”

Proteomics in Nutritional Systems Biology: Defining Health

“…She recently reviewed the influence of exposure to environmental micro-organisms on childhood asthma (Ege et al, 2011). At the same conference, Rolf Zinkernagel reported on long-lasting immunity conferred by early infection of infants who were protected by maternal antibodies (Navarini et al, 2010); and Per Brandtzaeg discussed secretory IgA and the intestinal barrier function as determinants of homeostasis and allergy (Brandtzaeg, 2010).…”