Post-vaccination Immune Response Research Articles

Evaluation of varicella zoster virus-specific cell-mediated immunity by using an interferon-γ enzyme-linked immunosorbent assay

BackgroundAdministration of the varicella vaccine induces both varicella-zoster virus (VZV)-specific humoral and cell-mediated immunity (CMI). ObjectiveTo assess VZV-CMI, we developed an interferon γ enzyme-linked immunosorbent assay (IFN-γ ELISA) that measures the quantity of total IFN-γ in culture supernatants of human peripheral blood mononuclear cells. Study designWe evaluated this method by comparing the pre- and post-vaccination immune response in peripheral blood mononuclear cells of 30 healthy children who were administered an initial varicella vaccination at Konan Kosei hospital. ResultsIFN-γ ELISA showed well-validated results; CMI was not detectable pre-immunization but became detectable post-immunization. Seroconversion was detected in 92.6% of subjects by the immune adherence hemagglutination test; however, half of the subjects did not display an increase in CMI levels. We also compared the incidence of breakthrough varicella and herpes zoster development between CMI post-positive and post-negative vaccinees at 1–2years after the last VZV vaccination. Eight subjects had a history of varicella or herpes zoster exposure post-VZV vaccination. Two of them with post-negative CMI contracted breakthrough varicella 15–16months after the last vaccination, even though they had sufficient VZV-specific antibody levels to be considered seropositive and seroprotected. Conversely, the others with post-positive CMI did not contract breakthrough varicella, despite experiencing extensive VZV exposure through casual contact with playmates and family. ConclusionsThe CMI data generated by this IFN-γ ELISA may accurately reflect real-world immune status, and CMI may be closely related to immunoprotection against breakthrough varicella development.

Impaired NK Cell Responses to Pertussis and H1N1 Influenza Vaccine Antigens in Human Cytomegalovirus-Infected Individuals.

NK cells contribute to postvaccination immune responses after activation by IL-2 from Ag-specific memory T cells or by cross-linking of the low-affinity IgG receptor, CD16, by Ag–Ab immune complexes. Sensitivity of NK cells to these signals from the adaptive immune system is heterogeneous and influenced by their stage of differentiation. CD56dimCD57+ NK cells are less responsive to IL-2 and produce less IFN-γ in response to T cell–mediated activation than do CD56bright or CD56dimCD57− NK cells. Conversely, NK cell cytotoxicity, as measured by degranulation, is maintained across the CD56dim subsets. Human CMV (HCMV), a highly prevalent herpes virus causing lifelong, usually latent, infections, drives the expansion of the CD56dimCD57+NKG2C+ NK cell population, skewing the NK cell repertoire in favor of cytotoxic responses at the expense of cytokine-driven responses. We hypothesized, therefore, that HCMV seropositivity would be associated with altered NK cell responses to vaccine Ags. In a cross-sectional study of 152 U.K. adults, with HCMV seroprevalence rate of 36%, we find that HCMV seropositivity is associated with lower NK cell IFN-γ production and degranulation after in vitro restimulation with pertussis or H1N1 influenza vaccine Ags. Higher expression of CD57/NKG2C and lower expression of IL-18Rα on NK cells from HCMV seropositive subjects do not fully explain these impaired responses, which are likely the result of multiple receptor–ligand interactions. This study demonstrates for the first time, to our knowledge, that HCMV serostatus influences NK cell contributions to adaptive immunity and raises important questions regarding the impact of HCMV infection on vaccine efficacy.

Immune response in pigs treated with therapeutic doses of enrofloxacin at the time of vaccination against Aujeszky's disease

The effect of treatment with enrofloxacin was studied on the postvaccinal immune response in pigs.Forty pigs were used (control not vaccinated (C), control vaccinated (CV), vaccinated, received enrofloxacin (ENRO)). From day −1 to day 3 pigs from ENRO group received enrofloxacin at the recommended dose. Pigs from ENRO and CV groups were vaccinated twice against Aujeszky's disease virus (ADV). There was a significant delay in the production of humoral response of enrofloxacin dosed pigs when compared with CV group. Moreover, in ENRO group the significant decrease in IFN-γ production and significantly lower values of stimulation index after ADV restimulation was noted, as compared with CV group. The secretion of IL-6, IL-10 and TNF-α by PBMC after recall stimulation was also affected in ENRO group.The results indicate that enrofloxacin, in addition to its antimicrobial properties, possess significant immunomodulatory effects and may alter the immune response to vaccines.

Identification of effective subdominant anti-HIV-1 CD8+ T cells within entire post-infection and post-vaccination immune responses.

Defining the components of an HIV immunogen that could induce effective CD8+ T cell responses is critical to vaccine development. We addressed this question by investigating the viral targets of CD8+ T cells that potently inhibit HIV replication in vitro, as this is highly predictive of virus control in vivo. We observed broad and potent ex vivo CD8+ T cell-mediated viral inhibitory activity against a panel of HIV isolates among viremic controllers (VC, viral loads <5000 copies/ml), in contrast to unselected HIV-infected HIV Vaccine trials Network (HVTN) participants. Viral inhibition of clade-matched HIV isolates was strongly correlated with the frequency of CD8+ T cells targeting vulnerable regions within Gag, Pol, Nef and Vif that had been identified in an independent study of nearly 1000 chronically infected individuals. These vulnerable and so-called “beneficial” regions were of low entropy overall, yet several were not predicted by stringent conservation algorithms. Consistent with this, stronger inhibition of clade-matched than mismatched viruses was observed in the majority of subjects, indicating better targeting of clade-specific than conserved epitopes. The magnitude of CD8+ T cell responses to beneficial regions, together with viral entropy and HLA class I genotype, explained up to 59% of the variation in viral inhibitory activity, with magnitude of the T cell response making the strongest unique contribution. However, beneficial regions were infrequently targeted by CD8+ T cells elicited by vaccines encoding full-length HIV proteins, when the latter were administered to healthy volunteers and HIV-positive ART-treated subjects, suggesting that immunodominance hierarchies undermine effective anti-HIV CD8+ T cell responses. Taken together, our data support HIV immunogen design that is based on systematic selection of empirically defined vulnerable regions within the viral proteome, with exclusion of immunodominant decoy epitopes that are irrelevant for HIV control.

Identification of Effective Subdominant Anti-HIV-1 CD8+ T Cells Within Entire Post-infection and Post-vaccination Immune Responses

Identification of Effective Subdominant Anti-HIV-1 CD8+ T Cells Within Entire Post-infection and Post-vaccination Immune Responses

Застосування препарату «Авесстим» для підвищення ефективності вакцинопрофілактики та вплив препарату на резистентність курчат

Investigated the Association of different infectious agents of viral and bacterial origin, the scheme vaccinations replacements birds conducted serological studies to determine the strength of the immune system of the bird, it is proved that the drug "Avastin increases post-vaccination antiviral immune response and as an immunostimulant may be recommended for the vaccination of poultry against viral diseases.

Adverse events and association with age, sex and immunological parameters of Q fever vaccination in patients at risk for chronic Q fever in the Netherlands 2011

BackgroundFollowing a large Q fever outbreak in the Netherlands, patients at risk for chronic Q fever received a whole-cell Q fever vaccine. Sensitized people were excluded based on pre-vaccination screening with skin test (ST) and serology. An investigational IFN-γ-production assay was added. No previous experience existed for Q fever vaccination in this patient risk-group with predefined cardiac valvular anomalies or aortic aneurysm/prosthesis and many co-morbidities. We studied the adverse events (AE) and their association with patient characteristics and immunological parameters. MethodsAE registration covered the week after skin test and 90 days following vaccination, with the use of diaries, interviews and spontaneous reports. Serious (S)AE were assessed immediately to ensure safety. We coded AE according to reported severity. Univariate and multivariate analysis addressed associations. ResultsPre-vaccination screening led to exclusion of 182 patients with positive serology and 207 patients with positive skin test-reading. The skin test did not lead to any causally related SAE. Subsequent vaccination of 1370 patients did not reveal unexpected AE; however, 80% of vaccinees reported local AE (in 26% of these pronounced or extensive). The two causally related SAE (0.1%) both concerned a persistent subcutaneous injection site mass. AE were more frequent in women, younger patients, and those without immunosuppressive co-morbidity/medication. The occurrence of local AE after skin test was associated with pre-vaccination positive serology and high IFN-γ production. This was also true for local AE following vaccination, with a strong association with local AE after skin test as well. The proportion of vaccinees with positive serology and positive IFN-γ values 6 months after vaccination was higher in those with local AE after skin test or after vaccination (non-significant, probably due to small numbers). ConclusionQ fever vaccination was safe but reactogenic in this high-risk patient-group. Rates of local AE were higher in women, younger age groups and in those with positive immunological parameters. Vaccinees with local AE after skin test or after vaccination appear to have more pronounced post-vaccination immune responses.

The effect of doxycycline treatment on the postvaccinal immune response in pigs

The effect of a seven-day antibiotic therapy with doxycycline was investigated on the postvaccinal humoral and cellular immune response in pigs. The selected parameters of non-specific immunity were also studied. Fifty pigs were used (control not vaccinated (C, n=10), control vaccinated (CV, n=20), and experimental — received doxycycline (DOXY, n=20)). For vaccination live-attenuated vaccine against pseudorabies (PR) was used. From day −1 to day 5 pigs from DOXY group received doxycycline orally with drinking water, at the recommended dose. Pigs from DOXY and CV groups were vaccinated at 8 and 10weeks of age. The results of the present study showed that cell-mediated postvaccinal immune response can be modulated by oral treatment with doxycycline. Significantly lower values of stimulation index were observed after PRV restimulation in doxycycline-treated pigs. Moreover, in the DOXY group a significant decrease in IFN-γ production after PRV restimulation was noted. The significantly lower number of CD4+CD8+ cells was also observed in doxy-treated, vaccinated pigs, 2weeks after final vaccination. Simultaneously, specific humoral response was not disturbed. This study demonstrated the importance of defining the immune modulatory activity of doxycycline because it may alter the immune responses to vaccines. The exact mechanism of T-cell response suppression by doxycycline remains to be elucidated, however the influence of doxycycline on the secretion of various cytokines, including IFN-γ, may be considered as a possible cause. The present observations should prompt further studies on the practical significance of such phenomena in terms of clinical implications.

Response of Viral Specific CD4 T Cells to in vitro Stimulation with Vaccine and Wild Measles Virus Strains in Vaccinated and Naturally Infected Subjects

With the implementation of the WHO strategic plan for the elimination of measles, the number of measles cases in European Region has decreased. However, outbreaks are still observed. Although most measles cases affect unvaccinated individuals, cases with vaccinated persons are also reported. Furthermore, it was described that a high percentage of young people in Poland exhibit no presence of anti-MeV IgG despite the high level of vaccination covering no less than 97% of the Polish population. Strong evidence exists that immunity to measles is complex and depends on both the humoral and cellular response and although antibodies have been used as correlates of immunity, it is increasingly being considered that antibody-based definitions of vaccine success or failure may be incomplete. Here, we investigated immunity to measles as the reactivity of CD4 T cells to stimulation with vaccine as well as wild strains of measles virus (MeV) isolated in Poland, in young vaccinated persons and subjects infected naturally. Evidence for the presence of MeV-specific memory cells years after infection or vaccination was found, however the cells ofvaccinees and naturally infected subjects reacted differently in contact with wild and vaccine MeV strains. Furthermore, the presence of a significant proportion of non-responder vaccinees was observed. In conclusion, our results may have implications for studies on the monitoring of the complexity of post-vaccine immune response.

Methodological principles for evaluating post-vaccination immune response

The article compares the experimental data obtained with the introduction of model antigens and defines principles for evaluating post-vaccination immune response based on the correlations between receptor activities of immunocompetent cells.

BALB/c mice, but not C57BL/6 mice immunized with a ΔclpB mutant of Francisella tularensis subspecies tularensis are protected against respiratory challenge with wild-type bacteria: Association of protection with post-vaccination and post-challenge immune responses

Francisella tularensis subspecies tularensis is highly virulent for humans especially when it is inhaled. Therefore, it has the potential to be used as a biothreat agent. Vaccines against F. tularensis will need to be approved in accordance with the FDA Animal Rule. This will require identification of robust correlates of protection in experimental animals and the demonstration that similar immune responses are generated in vaccinated humans. Towards this goal, we have developed an experimental live vaccine strain by deleting the gene, clpB, encoding a heat shock protein from virulent subsp. tularensis strain, SCHU S4. SCHU S4ΔclpB administered intradermally protects BALB/c, but not C57BL/6 mice from subsequent respiratory challenge with wildtype SCHU S4. A comparison of post-vaccination and post-challenge immune responses in these two mouse strains shows an association between several antibody and cytokine responses and protection. In particular, elevated IFNγ levels in the skin 2 days after vaccination, sero-conversion to hypothetical membrane protein FTT_1778c, and to 30S ribosomal protein S1 (FTT_0183c) of F. tularensis after 30 days of vaccination, and elevated levels of pulmonary IL-17 on day 7 after respiratory challenge with SCHU S4 were all associated with protection.

Immunoglobulin G subclass levels and antibody responses to the 2009 influenza A (H1N1) monovalent vaccine among human immunodeficiency virus (HIV)-infected and HIV-uninfected adults

Immunoglobulin (Ig)G levels are important for antibody vaccine responses and IgG subclass deficiencies have been associated with severe 2009 influenza A (H1N1) infections. Studies have demonstrated variations in immune responses to the H1N1 vaccine, but the aetiology of this is unknown. We determined the associations between pre-vaccination overall and influenza-specific IgG subclass levels and 2009 H1N1-specific antibody responses post-vaccination (robust versus poor at day 28) stratified by human immunodeficiency virus (HIV) status. Logistic regression models were utilized to evaluate whether pre-vaccination IgG subclass levels were associated with the antibody response generated post-vaccination. We evaluated 48 participants as part of a clinical study who were stratified by robust versus poor post-vaccination immune responses. Participants had a median age of 35 years; 92% were male and 44% were Caucasian. HIV-infected adults had a median CD4 count of 669 cells/mm(3) , and 79% were receiving highly active anti-retroviral therapy. HIV-infected participants were more likely to have IgG2 deficiency (<240 mg/dl) than HIV-uninfected individuals (62% versus 4%, P < 0·001). No association of pre-vaccination IgG subclass levels (total or influenza-specific) and the antibody response generated by HIN1 vaccination in either group was found. In summary, pre-vaccination IgG subclass levels did not correlate with the ability to develop robust antibody responses to the 2009 influenza A (H1N1) monovalent vaccine. IgG2 deficiencies were common among HIV-infected individuals but did not correlate with poor influenza vaccine responses. Further investigations into the aetiology of disparate vaccine responses are needed.

Immunogenicity and safety of heptavalent conjugate vaccine against Streptococcus pneumoniae in pre-term Polish infants

The purpose of the study was to assess post-vaccination immune response and occurrence of adverse events in the group of prematurely born infants. The study included 40 pre-term infants. Each child was vaccined four times (2, 4, 6 and 16 months) with the heptavalent conjugated pneumococcal vaccine (PCV7). Assessing of the level of antibodies was performed before vaccination, 4 weeks after primary series, before and 4 weeks after the booster dose. The research participants were qualified into 2 groups: group I – 19 children born before 30th gestational week, group II – 21 children born between the 30th and 34th gestational week. After the basic vaccination, an increase in the average antibody concentration in the area of all serotypes in most of the children tested was registered, with no significant differences observed between the groups. However, differences between individual serotypes were observed. The lowest values were found for serotype 6B. Before administering the booster dose, a significant drop in antibody titre in all of the children tested was noted. The last vaccination caused another significant increase in antibody concentration in both groups and the results obtained were markedly higher than those obtained after administering three vaccine doses. The majority of the children tested (with the exception of three from group II) achieved the preventive antibody level ≥0.35 μg/ml. In all of the children, no serious adverse events were observed. Our research showed, that heptavalent pneumococcal conjugate vaccine is immunogenic in children born before the completion of the 34th week of pregnancy. A booster dose of vaccine must be given at the right time to optimal response to the vaccine for all serotypes. Finally, any serious adverse events were observed.

Serological response to trivalent inactive influenza vaccine in HIV-infected children with different immunologic status

Influenza vaccination is usually recommended for HIV-infected children. One hundred and twenty seven HIV-infected and twenty-one HIV-uninfected children aged ≥6 months to <18 years, all of whom were naïve to influenza vaccine, were enrolled to receive an influenza Trivalent Inactivated Vaccine (TIV). In the HIV group, the post-vaccination immune response (geometric mean titer, seroconversion and seroprotection rates) correlated with their immunological status before vaccination. The HIV-infected children with no immunosuppression had comparable serological response to HIV-uninfected children. For moderately and severely immunosuppressed HIV groups, two doses of TIV resulted in greater serological responses and should be recommended in these groups.

Evaluation of vaccination results in high-risk patients included in hepatitis B vaccination program

Hepatitis B infection is one of the infectious diseases quite common in Turkey and around the world. Hepatitis B virus infection is a significant health problem which may cause chronic hepatitis, cirrhosis and hepatocellular carcinoma. With the introduction of Hepatitis B vaccine, a significant progress has been made in the prevention of HBV infections. The purpose of the study was to evaluate the characteristics of the individuals included in the risk group who admitted to our vaccination clinic, as well as their immune responses following the vaccination. Among the patients admitted to the vaccination clinic of our hospital between January 2003-December 2005 and that were included in the risk group (patients who have family members with chronic Hepatitis B infection, healthcare workers, hemodialysis patients etc.), those who were included in the vaccination program by examining the results of HBs Ag, anti-HBc and anti-HBs were evaluated in terms of their characteristics (age, gender, smoking etc.) and results of Anti-HBs score. A total of 958 people were included in the vaccination program. Upon evaluation in terms of risk factors, presence of patients with chronic hepatitis B infection in the family was found to be 80.6%(772/958), being healthcare worker was 9.2%(88/958), HCV positivity and chronic liver disease was 3.0%(29/958), being a hemodialysis patient was 2.8%(27/958), and being an oncology patient was 2.1%(20/958). Post-vaccination immune response could be evaluated in 69.8% (669/958) of patients and no responsiveness to vaccine was detected only in 8.1%(54/669) of them. Of the non-responders, 64.8% (35/54) were hemodialysis and oncology patients. Anti-HBs positivity rate following hepatitis B vaccination program was found compatible with the results of previous studies. With this vaccine of considerably high effectiveness, immunization of the entire community including primarily the risk groups should be targeted.

Characterization of neutralizing antibodies to Far Eastern of tick-borne encephalitis virus subtype and the antibody avidity for four tick-borne encephalitis vaccines in human

We assessed the humoral immunity of 290 vaccinated persons against tick-borne encephalitis (TBE). During the first year and 2 years after the primary three vaccinations the antibodies to the Far Eastern subtype tick-borne encephalitis virus strain P-73 were detected by neutralization test after immunization with FSME-Immune Inject vaccine (Baxter Vaccine AG, Austria) in 88.2% and 78.1% vaccinated persons, respectively; with Encepur ® Adult vaccine (Novartis Vaccines, Germany), in 100% and 100%; with the vaccine of the Chumakov Institute of Poliomyelitis and Viral Encephalitides RAMSci (Russia), in 100% and 94.1%; with EnceVir vaccine (Russia), in 88.2% and 83.9%; and after combined vaccination, in 100% and 92.7%. The dynamics of the decrease in IgG avidity index correlated with the changes of antibody titers determined by neutralization test. After the primary vaccination course, the titers of virus-neutralizing antibodies were high (6.3–7.4 log 2) when the avidity index of IgG antibodies were 31% and more; thus, this level can be considered immunologically significant. Two years after the primary vaccination course, the IgG avidity indexes of 60% and more can be regarded as significant on the background of the GMT decrease of virus-neutralizing antibodies. These results allow us to recommend all four vaccines for mass vaccination and an assay of IgG avidity, along with neutralization test, for a more adequate assessment of the level of postvaccination immune response.

Alum with Interleukin-12 Augments Immunity to a Melanoma Peptide Vaccine: Correlation with Time to Relapse in Patients with Resected High-Risk Disease

We attempted to augment immunity to melanoma antigens using interleukin-12 (IL-12) with aluminum hydroxide (alum) for sustained release or granulocyte macrophage colony-stimulating factor (GM-CSF) added to a multipeptide vaccine. Sixty patients with high-risk resected melanoma were randomized to receive melanoma peptides gp100(209-217) (210M), MART-1(26-35) (27L), and tyrosinase(368-376) (370D) with adjuvant Montanide ISA 51 and either IL-12 at 30 ng/kg with alum (group A), IL-12 at 100 ng/kg with alum (group B), or IL-12 at 30 ng/kg with 250 mug GM-CSF (group C). Three patients had stage IIC (5%), 50 had stage III (83%), and 7 had stage IV (12%) melanoma. Most toxicities were grade 1/2 and resolved rapidly. Significant toxicity included grade 3 colitis and visual changes and grade 3 headache resolving after stopping IL-12 but continuing peptide vaccine. A higher rate of post-vaccine 6-month immune response to gp100 and MART-1 was observed in group A (15 of 19) or B (19 of 20) that received IL-12 plus alum versus group C with IL-12/GM-CSF (4 of 21; P < 0.001). Post-vaccine enzyme-linked immunospot response rates to peptide analogues in group B were higher than group A (P = 0.031 for gp100 and P = 0.010 for MART-1); both were higher than group C (P < 0.001 for gp100 and P < 0.026 for MART-1). With a median of 24 months of follow-up, 23 patients have relapsed. Post-vaccine immune response to MART-1 was associated with relapse-free survival (P = 0.012). IL-12 with alum augmented an immune response to melanoma antigens compared with IL-12 with GM-CSF. Immune response was associated with time to relapse.

Measles Virus–Specific IgG4 Antibody Titer as a Serologic Marker of Post-vaccinal Immune Response

In previous research, we concluded that measles virus specific IgG4 antibody titer could be used to differentiate between natural [IgG4 GMT 80 (95% CI, 33 to 191)] and vaccinal source of measles infection [IgG4 GMT 13 (95% CI, 7 to 26)]. The aim of this paper is to show that this new serologic marker (IgG4 measles antibody titer) can be applied to help interpret rare but well documented cases of measles Ig M-positive results in vaccinated individuals who, 1-2 months after vaccination, developed rash and fever and therefore do not meet the criteria for post-vaccinal measles infection. Six measles IgM-positive serum samples obtained from measles vaccinated individuals who developed rash/fever 1 to 2 months post-vaccination were studied by Immunofluorescence assay for the quantification of IgG4 measles specific antibody. IgG4 antibody titers from all these samples were between 1:10-1:20, consequently, the IgM positive results from the study cases could be ascribed to post-vaccinal immune response. Thus, measles virus specific IgG4 antibody titer could be used as a serologic marker of post-vaccinal immune response.

The influence of marginal zinc deficient diet on post-vaccination immune response against hepatitis B in rats

To evaluate in vitro T lymphocyte proliferation and specific antibody response to hepatitis B vaccination in two groups of rats fed with normal and marginal zinc content. Twenty-two Wistar-Albino rats were randomly assigned into two groups and were fed with constant diet. Zinc was suplemented 10mg/kg dry weight in group I (marginal zinc content) (n=14) and 30mg/kg dry weight in group II (n=8). Hepatitis B vaccine (Engerix B, 4mug) was administered intramuscularly after 8 weeks on feeding and a booster dose was applied 4 weeks after the first injection. Rats were killed 3 weeks after the second injection. Peripheral blood mononuclear cells were stimulated in vitro by PHA (2.5mug/ml) and hepatitis B surface antigen (2.5, 5, 10mug/ml). Proliferation was evaluated by ELISA (celltiter-96 aqueous one solution cell proliferation assay). Serum zinc, anti-HBs titer and zinc per dry liver weight were also measured. Two groups were compared with respect to antigen specific antibody and lymphocyte proliferation responses. Proliferation response to HbsAg were expressed as net percent increase (pci) in lymphocyte proliferation from the baseline activity. Rats' mean body weight and weight gain per month were similar. Median serum zinc was 39 (23-75) and 76(64-115)mug/dl of groups I and II rats, respectively (p<0.05), while there was no difference in liver zinc content between the two groups (37mug/g dry weight versus 32mug/g dry weight). Median anti-HBs levels of groups I and II were 741 (0-10,000)IU/l, 5791 (558-10,000)IU/l, respectively (p<0.05). In lymphocyte proliferation assays, mean net pci with HbsAg of 5 and 10mug/ml were 9.4% and 11.3% in group I rats; while they were 25.3% and 26.1% in group II rats (p<0.01 and p<0.01, respectively). In vitro cell-mediated immune response and in vivo specific antibody response to hepatitis B vaccine was decreased in rats fed a diet with marginal zinc content. These observations have shown that marginal Zn deficiency might influence the efficacy of hepatitis B vaccination in humans.

Helminthiasis: new medical significance

Dan Colley et al. [1xMedical helminthology in the 21st Century. Colley, D.G. et al. Science. 2001; 293: 1437–1438Crossref | PubMed | Scopus (72)See all References[1] suggested that an ‘Affirmative Action for Worms’ research-funding program should be established. Their idea is aimed at reversing ‘the current downward spiral of research’ in the field of medical helminthology. In supporting this proposal, Paul Hagan accurately comments: ‘The essential shift of focus to HIV/AIDS…tuberculosis and malaria could be responsible for the decline in helminth research’ [2xThis wormless world. Hagan, P. Trends Parasitol. 2001; 17: 569Abstract | Full Text | Full Text PDFSee all References[2].I wish to make a tongue-in-cheek observation that research on HIV/AIDS, TB, malaria and allergy should become part of research on helminthiasis. Worm infestations diminish the efficacy of certain types of vaccine against various diseases, including TB [3xWorms and tuberculosis vaccines. Markus, M.B. Trends Microbiol. 2001; 9: 474Abstract | Full Text | Full Text PDF | PubMed | Scopus (2)See all References[3] and, perhaps, HIV/AIDS and malaria [4.xHelminthic infection and HIV vaccine trials. Markus, M.B. and Fincham, J.E. Science. 2001; 291: 46–47Crossref | PubMed | Scopus (9)See all References, 5.xHelminthiasis and HIV vaccine efficacy. Markus, M.B. and Fincham, J.E. Lancet. 2001; 357: 1799Abstract | Full Text | Full Text PDF | PubMedSee all References, 6.xMalaria vaccine trials in a wormy world. Nacher, M. Trends Parasitol. 2001; 17: 563–565Abstract | Full Text | Full Text PDF | PubMed | Scopus (36)See all References]. Deworming before vaccination has been shown (for vaccines against more than one non-helminthic disease) to enhance the post-vaccination immune response, but additional studies are urgently needed [3.xWorms and tuberculosis vaccines. Markus, M.B. Trends Microbiol. 2001; 9: 474Abstract | Full Text | Full Text PDF | PubMed | Scopus (2)See all References, 5.xHelminthiasis and HIV vaccine efficacy. Markus, M.B. and Fincham, J.E. Lancet. 2001; 357: 1799Abstract | Full Text | Full Text PDF | PubMedSee all References]. Moreover, it has been suggested that ascariasis is associated with protection from cerebral malaria [6xMalaria vaccine trials in a wormy world. Nacher, M. Trends Parasitol. 2001; 17: 563–565Abstract | Full Text | Full Text PDF | PubMed | Scopus (36)See all References[6]; and Bentwich's hypothesis [7.xGood worms or bad worms: do worm infections affect the epidemiological patterns of other diseases?. Bundy, D. et al. Parasitol. Today. 2000; 16: 273–274Abstract | Full Text | Full Text PDF | PubMed | Scopus (59)See all References, 8.xMbeki and AIDS in Africa. Markus, M.B. and Fincham, J.E. Science. 2000; 288: 2131Crossref | PubMedSee all References] is that the immunological consequences of various helminthic infestations are likely to predispose individuals to infection with HIV and Mycobacterium tuberculosis and/or accelerate progression of clinical illness caused by these two organisms. Lastly, there appear to be important, interesting and puzzling interactions between atopy and helminthiasis, which are only now starting to be investigated properly [9.xTh2 responses without atopy: immunoregulation in chronic helminth infections and reduced allergic disease. Yazdanbakhsh, M. et al. Trends Immunol. 2001; 22: 372–377Abstract | Full Text | Full Text PDF | PubMed | Scopus (209)See all References, 10.xWorms and allergy. Markus, M.B. Trends Immunol. 2001; 22: 598–599Abstract | Full Text | Full Text PDF | PubMedSee all References].The considerable public health significance of all these possible correlations and new findings is self-evident and provides support for the program suggested by Colley et al. [1.xMedical helminthology in the 21st Century. Colley, D.G. et al. Science. 2001; 293: 1437–1438Crossref | PubMed | Scopus (72)See all References, 2.xThis wormless world. Hagan, P. Trends Parasitol. 2001; 17: 569Abstract | Full Text | Full Text PDFSee all References].