Naturally-acquired Immunity Research Articles

Chapter 21: Modelling the impact of HPV vaccines on cervical cancer and screening programmes

The impact of human papillomavirus (HPV)-16/18 vaccination on the incidence of infection and disease can be explored in a range of different models. Here we explore the epidemiological and economic impact of vaccination where screening is absent and where it is well established. The importance for epidemiology of assumptions about naturally-acquired immunity and heterogeneity in risk behaviours are highlighted, as are the importance for health economic outcomes of vaccine costs and the ability to modify screening strategies. To date, model results are consistent in predicting a useful role for vaccine, but further epidemiological data are required to help test the validity of models.

Naturally-acquired immunity to Neisseria meningitidis group A

Group A meningococcal disease is epidemic in Sudan, less common in Uganda, a country bordering the “meningitis belt,” and rare in North America. The basis of naturally-acquired group A immunity is unknown but in North America protection has been attributed to a high prevalence of serum anticapsular antibodies elicited by cross-reacting bacteria. We measured group A anticapsular antibody concentrations and bactericidal titers in sera from 236 adults (47 from the Sudan obtained at the height of a group A epidemic, 57 from Uganda, and 132 from North America). Anticapsular antibody concentrations were higher in Sudanese sera than in North American or Ugandan sera (geometric mean of 31.5 versus 5.4 and 5.3 μg/ml, respectively, P < 0.0001). Bactericidal titers of ≥1:4 (presumed to be a protective titer when measured with human complement) were detected in 66% of Sudanese sera as compared with 27 and 23%, respectively, of North American and Ugandan sera ( P < 0.0001). Bactericidal activity was inhibited by group A polysaccharide in 58% of the Sudanese bactericidal sera as compared to 17 and 6% of North America and Ugandan bactericidal sera ( P < 0.0005). Approximately 50% of non-bactericidal Sudanese sera had high IgA anticapsular antibody concentrations, which were rare in bactericidal Sudanese sera. Thus, serum anticapsular antibodies and bactericidal activity are prevalent in Sudanese exposed to a group A epidemic. Cross-reacting group A anticapsular antibodies are prevalent in North American and Ugandan sera, but bactericidal activity is infrequent and when present is largely directed at non-capsular antigens.

Human cytokine responses to meso-endemic malaria on the Pacific Coast of Colombia.

Studies of naturally-acquired immunity to malaria in endemic regions provide the potential for a greater understanding of the regulation of human immune responses to the malarial parasite. However, little is known about the acquisition of malaria-specific immunity in regions of unstable, meso-endemic or hypo-endemic transmission. Cytokine profiles - patterns in the expression of interleukin-4 (IL-4), interleukin-10, interleukin-12, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) - were therefore studied during the natural acquisition of immunity to Plasmodium falciparum and P. vivax among individuals from Buenaventura, a meso-endemic region on the Pacific Coast of Colombia. In general, specific type-1 immune responses, characterized by IFN-gamma expression, were more likely to develop during P. falciparum infection, whereas pro-inflammatory cytokine profiles (with TNF-alpha expression) were observed more frequently among the P. vivax infections. Type-2 cytokine profiles, characterized by dominant IL-4 expression, were infrequent. Expression of IL-4 probably occurs primarily after prolonged exposure to parasites (which would, by definition, not be common in a meso-endemic region).

Varicella in Americans from NHANES III: Implications for control through routine immunization

At the time of varicella vaccine introduction in the United States, an estimated 4 million episodes of varicella occurred annually. This survey of varicella seroprevalence is the first to describe immunity to a vaccine-preventable disease prior to vaccine introduction in the United States population. The objective of this analysis is to describe patterns of naturally-acquired varicella and understand characteristics associated with infection in the varicella vaccine-naive United States population. A nationally representative cross-sectional health examination survey that included venipuncture was conducted among 21,288 U.S. participants aged 6 years and older from 1988 through 1994. Serologic evidence of varicella-zoster virus infection was measured by enzyme immunoassay of varicella-zoster virus-specific IgG antibody. The seroprevalence of IgG antibody to varicella-zoster virus increased from 86.0% in children aged 6 through 11 years to 99.6% in adults aged 40 through 49 years. Immunity to varicella remained at 99% or higher in Americans aged 50 years and older. Among persons aged 6 through 19 years, non-Hispanic black children were 40% less likely to be seropositive compared with white children (odds ratio [OR], 0.6; 95% confidence interval [CI], 0.4-0.8). Among young adults aged 20 through 39 years, women with a history of live birth (OR, 4.3; 95% CI, 2.1-8.7) and married men (OR, 2.7; 95% CI, 1.2-5.7) were more likely to have naturally-acquired immunity to varicella. This study found that, prior to use of varicella vaccine in the United States, age, race, and marital characteristics were independently associated with naturally acquired varicella. Future varicella serosurveys in Americans will provide essential information to interpret the population impact of varicella vaccine.

Incidence of symptomatic and asymptomatic Plasmodium falciparum infection following curative therapy in adult residents of northern Ghana.

Adult residents of holoendemic malaria regions in Africa have a naturally acquired immunity (NAI) to malaria that renders them more resistant to new infections, limits parasitemia, and reduces the frequency and severity of illness. Given such attributes, it is not clear how one might evaluate drug or vaccine efficacy in adults without serious confounding. To determine symptomatic and asymptomatic malaria attack rates in adults of northern Ghana, 197 men and women underwent curative therapy for any pre-existing malaria infections at the start of the high transmission (wet) season. They were monitored for first parasitemia and first clinical episode of infection by Plasmodium falciparum over a 20-week period (May-October 1996). The cumulative incidence of primary infection by P. falciparum was 0.98 and incidence density of infection was calculated to be 7.0 cases/person-year. Symptoms were reported by 19.5% of the individuals at the time of first recurrent parasitemia. Incidence of infection, parasite density, and the frequency of symptoms were comparable in males and females. The results suggest that NAI did not provide these adults with significant defense against rapid re-infection and suggest that this population-infection design could serve to demonstrate the efficacy of a drug or vaccine in preventing parasitemia.

Depletion of IFN-gamma, CD8+ or Tcr gamma delta+ cells in vivo during primary infection with an enteric parasite (Trichostrongylus colubriformis) enhances protective immunity.

In order to examine the role of CD8+ and WCI+ T cells and of IFN-gamma in the development of protective immunity against infection with the enteric nematode parasite Trichostrongylus colubriformis in sheep, mAb were administered during induction of the immune response to deplete or neutralize these components. Protection against the primary and challenge infections were assessed by faecal egg count and total worm count. Prolonged administration of mAb recognizing IFN-gamma and CD8+ resulted in significantly increased protection during the 6-week primary infection. CD8+ cells were depleted from blood but not intestinal mucosa. After injection of mAb (CC15) recognizing the surface antigen WCI, WCI+ and T cell receptor (Tcr) gamma delta+ cells were depleted from blood but not from enteric mucosa, and protection against challenge, although variable, was increased by up to 88%. It appears that CD8+ and WCI+/gamma delta+ cells and IFN-gamma all retard the potential development of naturally-acquired immunity against the parasite.

Epitopes in the 19kDa fragment of the Plasmodium falciparum major merozoite surface protein‐1 (PfMSP‐119) recognized by human antibodies

The antibody response to two different epitopes located in the C-terminal 19kDa fragment of the Plasmodium falciparum merozoite surface protein-1 (MSP-1(19)) has been studied using a competitive ELISA based on the inhibition of monoclonal antibody (MoAb) binding by serum samples. Sera from children aged three to eight years who suffered clinical symptoms of malaria, or were partially immune with an asymptomatic infection, and from adults all living in The Gambia, West Africa were tested. The results suggest that the antibody response to MSP-1(19) has a role in naturally-acquired immunity in Gambian individuals.

International efforts to measure health expectancy.

<h3>Abstract</h3> <h3>Objectives</h3> There are paucity of studies examining naturally acquired immunity against SARS-CoV-2 in children and adolescents, though they are generally the last group to be afforded the vaccine, and a significant portion of them are still unvaccinated. This study examined the duration of protection conferred by a previous SARS-CoV-2 infection amongst children and adolescents. <h3>Design</h3> A retrospective study, applying two complementary approaches: a matched test-negative case control design and a retrospective cohort design. <h3>Setting</h3> Nationally centralized database of Maccabi Healthcare Services, an Israeli national health fund that covers 2.5 million people. <h3>Participants</h3> The study population included between 293,743 and 458,959 individuals (depending on the model), 5-18 years of age, who were unvaccinated SARS-CoV-2 naïve persons or unvaccinated convalescent patients. <h3>Main outcomes and measures</h3> Analyses focused on the period of July 1 to December 13, 2021, a Delta-dominant period in Israel. We evaluated three SARS-CoV-2-related outcomes: (1) documented PCR confirmed infection or reinfection, (2) COVID-19 and (3) severe COVID-19. <h3>Results</h3> Overall, children and adolescents who were previously infected acquired durable protection against reinfection (symptomatic or not) with SARS-CoV-2 for at least 18 months. Importantly, no COVID-19 related deaths were recorded in either the SARS-CoV-2 naïve group or the previously infected group. Effectiveness of naturally-acquired immunity against a recurrent infection reached 89.2% (95% CI: 84.7%-92.4%) three to six months after first infection, mildly declining to 82.5% (95% CI, 79.1%-85.3%) nine months to one year after infection, then remaining rather steady for children and adolescents for up to 18 months, with a slight non-significant waning trend. Additionally, we found that ages 5-11 exhibited no significant waning of naturally acquired protection throughout the outcome period, whereas waning protection in the 12-18 age group was more prominent, but still mild. <h3>Conclusions</h3> Children and adolescents who were previously infected with SARS-CoV-2 remain protected against reinfection to a high degree for 18 months. Policy decision makers should consider when and if convalescent children and adolescents should be vaccinated. Nonetheless, further research is needed to examine naturally acquired immunity against emerging variants, including the Omicron.

Diffusion and physiological responses to the influenza pandemic of 1918–19 in Nigeria

Although virologists are not in agreement on the origins of the 1918–19 influenza pandemic, it has long been associated with the virulent type A virus. At least 21 million people died from the disease over a 12-month period, becoming one of the world's worst short-term demographic disasters. The disease was introduced into Nigeria by passengers and crews who arrived via ship from overseas. Thus, coastal ports were the primary focus of the diffusion of the disease. Its spread to the hinterland was facilitated by improvements in transportation technology. Neither maritime quarantine, nor the isolation of patients checked the spread of the disease. About 500,000 Nigerians, out of a population of 18 million, died in less than 6 months, and between 50 and 80% of the population was stricken. The over-crowded urban centers were the hardest hit and, even though the pandemic declined almost as suddenly as it began, morbidity, mortality, and panic adversely affected the productive capacity of the country. Since the 1930s, virologists have gained much knowledge about the agents responsible for influenza diffusion, but the disease remains one of the few plagues to be eradicated. This is partly because of the exceptional adaptability of influenza viruses, and partly because both artificially and naturally-acquired immunity to influenza are temporary in duration, making reinfection possible even by the same type or subtype of influenza.

Immunological approaches to the control of ticks

It has now been amply demonstrated that it is possible to induce an immunologically-mediated resistance to several tick species using crude extracts. This is the first step on a long road to a practical means of tick control. The next step must be the identification of protective antigens and this work has hardly been started. It must be remembered that one cannot even gauge the eventual effectiveness of a vaccine from experiments with crude extracts: as antigen purification proceeds, the effectiveness may increase (due to the removal of irrelevant antigens) or fall (due to the separation of a multiplicity of synergistic antigens). On a more optimistic note, it has now been shown that immunity to ticks can be produced using concealed antigens. This has several possible advantages. It may be intrinsically more effective than naturally-acquired immunity; it may act synergistically with naturally-acquired immunity and finally, and this is pure speculation, it may be harder for the prasite to circumvent than naturally-acquired immunity. In any event, one may perhaps be cautiously optimistic that an immunological alternative to the chemical control of ticks may be developed in the not-too-distant future.

Natural immunity to measles, rubella and mumps among Spanish children in the pre-vaccination era.

Prior to the start of mass vaccination campaigns against measles, rubella and mumps, a prevalence study of natural immunity to these diseases was undertaken in a sample of 1700 unvaccinated Spanish children. They were representative of the 3-7 year-old population in terms of age, regional distribution and urban or rural environment. Measles infection prevalence was significantly higher than that for rubella and mumps from 3 (48.3%, 14.2%, 25.5%, respectively) through 7 years of age, (64%, 40.9%, 39%). As a function of age, naturally-acquired immunity increased according to parabolic progressions. In the 3-5 year-old group, rural environment, low socioeconomic status, no school attendance and lack of brothers were associated with statistically lower levels of measles, rubella, or mumps infection. In the 6-7 year-old group, only 12% of the children showed antibodies against the three diseases and 18.7% exhibited triple susceptibility.

Haemonchosis in white-tailed deer in the southeastern United States.

Haemonchosis concomitant with malnutrition has been a frequent parasitic disease observed in white-tailed deer (odocoileus virginianus) in the southeastern United States. Typically, afflicted deer were fawns from the southeastern coastal plain, and most cases were submitted between October and March. A survey of deer from 14 areas along the Atlantic coast revealed that fawns had significantly higher numbers of Haemonchus contortus than adults and in some areas fawns harbored H. contortus burdens that were considered pathogenic. The lower H. contortus burdens in adult deer suggested a naturally-acquired immunity. This hypothesis was supported by a trial in which challenge of small groups of Haemonchus-naive and previously exposed penned deer resulted in poorer performance of H. contortus in previously exposed deer. This study indicated that during their first winter fawns are particularly vulnerable to a haemonchosis/malnutrition syndrome.

The Susceptibility of African Wild Animals to Yellow Fever 1

SummaryTests of susceptibility to yellow fever virus were made in Perodicticus potto ibeanus and Galago crassicaudatus lasiotis. The potto was found to be susceptible, in that the virus propagates in it and is present in its blood in considerable quantity for several days. The galagos were even more highly susceptible, exhibited circulating virus in higher titre and about half of them died of the disease. It was found that they may be infected by a dose of virus which is much too small to cause specific infection in white mice. Yellow fever virus was transmitted from one galago to another by the bites of 2 Aëdes africanus. Naturally-acquired immunity to yellow fever was found in galagos captured in the coastal area of Kenya Colony. The results indicate that some species of this genus may be of considerable importance in the epidemiology of extrahuman cycles of the disease.About 50 per cent of infected galagos exhibit an emerald green coloration of the serum for 2 to 5 days, coinciding roughly with the period of circulating virus.The lesions induced by yellow fever virus in galagos, although similar in the gross to those in man and rhesus monkeys, differ in their microscopic aspects. Neither inclusion bodies nor acidophilic necrosis of hepatic cells were observed in them; the microscopic lesions are therefore less conspicuous in galagos.