Post-vaccination Immune Response Research Articles

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].

Immunogenicity and tolerance of a 7-valent pneumococcal conjugate vaccine in nonresponders to the 23-valent pneumococcal vaccine.

There is still a lack of effective vaccination strategies for patients with a deficient antibody response to bacterial polysaccharide antigens. In an open trial, we evaluated the immunogenicity and tolerance of a new 7-valent pneumococcal conjugate vaccine in 22 infection-prone nonresponders to pneumococcal polysaccharide vaccine and 21 controls. In the patient group, nonresponsiveness was confirmed by repeated vaccination with a 23-valent pneumococcal polysaccharide vaccine. The study protocol provided two doses of the pneumococcal conjugate vaccine, given 4 to 6 weeks apart, for both groups. The antibody response was determined before each vaccination and on follow-up by an enzyme-linked immunosorbent assay and compared to the response in a functional opsonophagocytosis assay. Patients showed a significantly lower postvaccination immune response for all serotypes than did controls. The postvaccination response was serotype dependent. A median titer of >1 microgram/ml in patients was recorded only for serotypes 4, 9V, 14, and 19F, which are known to be more immunogenic than serotypes 6B, 18C, and 23F. In the patient group, 70% responded to serotype 19F (Pnc 19F), 65% responded to Pnc 14 and 4, 60% responded to Pnc 9V, 55% responded to Pnc 18C, 50% responded to Pnc 23F, and 25% responded to Pnc 6B. In the control group >95% of individuals showed a titer of >1 microgram/ml to every serotype. The vaccine was tolerated well, and no major side effects have been reported. The new pneumococcal conjugate vaccine is clearly more immunogenic in previous nonresponders than is the 23-valent pneumococcal vaccine. Immunization with a pneumococcal conjugate vaccine should be considered as a strategy to protect high-risk patients.

Cutaneous and subcutaneous granulomata formation in mice immunized and challenged with third-stage infective hookworm ( Ancylostoma caninum) larvae

To determine the inflammatory and immunological mechanisms associated with live third-stage (L 3) hookworm larval vaccines, mice were immunized either subcutaneously or orally with three doses of 500 L 3 of Ancylostoma caninum at 2-week intervals, and then challenged percutaneously (via abdominal skin) with 500 L 3. Non-immunized mice served as negative controls. Skin was excised from post-challenge mice at intervals between 6 h and 28 days, and then examined by light microscopy. In non-immunized mice the L 3 exhibited no structural damage and infiltrating inflammatory cells were absent from the surrounding tissues. There were no changes in the cutaneous architecture. In contrast, skin recovered from the immunized mice was edematous and exhibited marked inflammatory changes with resultant destruction of the challenge L 3. At 6 h post-challenge the L 3 exhibited cuticular swelling and damage; the surrounding tissue was infiltrated by polymorphonuclear inflammatory cells. By 24 h granulomata in the dermis, subcutaneous tissues and underlying abdominal muscles were first observed surrounding dead L 3. The number of granulomata peaked at 72 h, with the majority distributed in the subcutaneous tissues. Plasma cells predominated in the early granulomata, but by 3–7 days post-challenge foreign body giant cells began to appear. In some cases, intact and presumably living L 3 were noted in the abdominal muscles 14–28 days post-challenge, which suggested that protection against larval challenge was not absolute. Granuloma formation appears to be a major component of the post-vaccination murine host immune response against challenge larvae. The observation generates several hypotheses to investigate the mechanisms of protection afforded by living helminth vaccines.

Postvaccinal immune response to regimens of Newcastle disease vaccination by filter paper sampling technique.

Seven hundred and ten blood samples were collected at random from commercial layers in Tamil Nadu on Whatman filter paper No. 1 instead of the conventional method of serum collection. The birds were subjected to different Newcastle disease (ND) vaccination schedules and samples were collected to study the vaccinal response to ND at field level. Eluates were obtained from sample areas of filter paper using Brij-35 solution [detergent] and subjected to the micro haemagglutination inhibition (HI) test for ND antibodies. The HI titre ranged from less than 2(4) to 2(9). The possible causes of poor immune response to ND vaccinations are discussed.

BCG vaccination in low birth weight newborns: Analysis of lymphocyte proliferation, IL-2 generation and intradermal reaction to PPD

Objective: To study vaccinal scar formation and post-vaccinal immune response in newborns with birth weight ranging from 2000 to 2499 g vaccinated in the first week of life with intradermal bacille Calmette-Guérin (BCG) (Moreau-Rio de Janeiro strain). Method: Specific immune response to PPD was assessed in 30 low birth weight newborns (mean birth weight = 2311.7 ± 122.1 g; mean gestational age = 38.1 ± 1.8 weeks) in comparison to 56 control infants (mean birth weight = 3198.9 ± 267.2 g; mean gestational age = 38.5 ± 1.2 weeks). Results: Low birth weight infants have an efficient immune response to vaccinal stimulus when compared to control infants as judged by specific in vitro lymphocyte proliferation (mean SI = 9.7 ± 12.9 vs SI = 8.8 ± 10.0, P = 0.72) and IL-2 production (mean SI = 3.1 ± 3.4 vs SI = 2.6 ± 2.0, P = 0.38). Intradermal reaction to PPD was also comparable in both groups (mean induration diameter = 9.5 ± 5.1 mm vs 9.6 ± 5.0 mm, P = 0.94). Conclusion: These data suggest that low birth weight newborns show a good immune response to BCG, thus reinforcing the inclusion of such infants in regular vaccination programs with intradermal BCG.