Intradermal Booster Research Articles

One-dose intradermal rabies booster enhances rabies antibody production and avidity maturation

The incidence of rabies in Thailand reached its peak in 2018 with 18 human deaths. Preexposure prophylaxis (PrEP) vaccination is thus recommended for high-risk populations. WHO has recently recommended that patients who are exposed to a suspected rabid animal and have already been immunized against rabies should receive a 1-site intradermal (ID) injection of 0.1 mL on days 0 and 3 as postexposure prophylaxis (PEP). In Thailand, village health and livestock volunteers tasked with annual dog vaccination typically receive only a single lifetime PrEP dose and subsequent boosters solely upon confirmed animal bites. However, the adequacy of a single PrEP dose for priming and maintaining immunity in this high-risk group has not been evaluated. Therefore, our study was designed to address two key questions: (1) sufficiency of single-dose PrEP—to determine whether a single ID PrEP dose provides adequate long-term immune protection for high-risk individuals exposed to numerous dogs during their vaccination duties. (2) Booster efficacy for immune maturation—to investigate whether one or two additional ID booster doses effectively stimulate a mature and sustained antibody response in this population. The level and persistence of the rabies antibody were determined by comparing the immunogenicity and booster efficacy among the vaccination groups. Our study demonstrated that rabies antibodies persisted for more than 180 days after cost-effective ID PrEP or the 1st or the 2nd single ID booster dose, and adequate antibody levels were detected in more than 95% of participants by CEE-cELISA and 100% by indirect ELISA. Moreover, the avidity maturation of rabies-specific antibodies occurred after the 1st single ID booster dose. This smaller ID booster regimen was sufficient for producing a sufficient immune response and enhancing the maturation of anti-rabies antibodies. This safe and effective PrEP regimen and a single visit involving a one-dose ID booster are recommended, and at least one one-dose ID booster regimen could be equitably implemented in at-risk people in Thailand and other developing countries. However, an adequate antibody level should be monitored before the booster is administered.

Intradermal delivery of the third dose of the mRNA-1273 SARS-CoV-2 vaccine: safety and immunogenicity of a fractional booster dose

ObjectivesThe aim of this study was to assess the safety and immunogenicity of a dose-sparing fractional intradermal (ID) booster strategy with the mRNA-1273 COVID-19 vaccine. MethodsCOVID-19 naive adults aged 18–30 years were recruited from a previous study on primary vaccination regimens that compared 20 μg ID vaccinations with 100 μg intramuscular (IM) vaccinations with mRNA-1273 as the primary vaccination series. Participants previously immunized with ID regimens were randomly assigned (1:1) to receive a fractional ID booster dose (20 μg) or the standard-of-care intramuscular (IM) booster dose (50 μg) of the mRNA-1273 vaccine, 6 months after completing their primary series (ID-ID and ID-IM group, respectively). Participants that had received a full dose IM regimen as the primary series, received the IM standard-of-care booster dose (IM-IM group). In addition, COVID-19 naive individuals aged 18–40 years who had received an IM mRNA vaccine as the primary series were recruited from the general population to receive a fractional ID booster dose (IM-ID group). Immunogenicity was assessed using IgG anti-spike antibody responses and neutralizing capacity against SARS-CoV-2. Cellular immune responses were measured in a sub-group. Safety and tolerability were monitored. ResultsIn January 2022, 129 participants were included in the study. Fractional ID boosting was safe and well tolerated, with fewer systemic adverse events compared with IM boosting. At day 28 post-booster, anti-spike S1 IgG geometric mean concentrations were 9106 (95% CI, 7150–11 597) binding antibody units (BAU)/mL in the IM-IM group and 4357 (3003–6322) BAU/mL; 6629 (4913–8946) BAU/mL; and 5264 (4032–6873) BAU/mL in the ID-IM, ID-ID, and IM-ID groups, respectively. DiscussionIntradermal boosting provides robust immune responses and is a viable dose-sparing strategy for mRNA COVID-19 vaccines. The favourable side-effect profile supports its potential to reduce vaccine hesitancy. Fractional dosing strategies should be considered early in the clinical development of future mRNA vaccines to enhance vaccine availability and pandemic preparedness.

Immunogenicity and reactogenicity of repeated intradermal mRNA COVID-19 vaccines administered as a second booster dose in a Thai geriatric population.

Geriatric populations are at an increased risk of severe presentations, hospitalization, and loss of life from COVID-19. Few studies have explored vaccination regimens in adults >65 years old. Repeated booster vaccination is required for high-risk populations as COVID-19 vaccine efficacy is short-lived. We compared the immunogenicity and reactogenicity of second intradermal (ID) COVID-19 booster vaccination with second intramuscular (IM) vaccination in older adults. This single-center, open-labeled, prospective, cohort study conducted at Siriraj Hospital enrolled older adults ≥65 years old who previously received a first booster (third dose) mRNA vaccine (mRNA-1273 or BNT162b2) via ID or IM administration. Participants were allocated to receive a second booster of the same vaccine type and route as their first booster 16-17 weeks thereafter. Anti-SARS-CoV-2 receptor binding domain IgG and neutralizing antibody titers against Wuhan and Omicron subvariants (BA.1, BA.2, and BA.4/5) were measured 2 weeks after vaccination. Of 91 enrolled participants, 72.5% were women, with a median age of 75 years. Forty-nine participants (53.8%) received a second ID booster, and 42 (46.2%) received a second IM booster. Two weeks after the second booster, all groups generated anamnestic IgG antibody responses that were 5.41- to 10.00-fold higher than at baseline. Overall, higher antibody GMTs against Wuhan and Omicron subvariants were observed in IM compared with ID regimens. ID mRNA-1273 induced similar GMTs to IM BNT162b2 2 weeks after the second booster against Wuhan (486.77 [321.48, 737.05] vs. 472.63 [291.24, 767.01], respectively; p = 0.072). Higher GMTs against Omicron BA.1 (GMR [95% CI], 1.71 [1.39, 2.11]; p = 0.023), BA.2 (1.34 [1.11, 1.62]; p = 0.845), and BA.4/5 (1.10 [0.92, 1.33]; p = 0.531) were seen in all groups at 2 weeks after the second booster compared with 2-4 weeks after the first booster. Both local and systemic AEs were less frequent after the second than after the first booster, regardless of administrative route and vaccine type. Local AEs were significantly more frequent in ID mRNA-1273 arms than their respective BNT162b2 arms 2 weeks after the second booster (ID-mRNA-1273 vs. ID-BNT162b2: p ≤ 0.001). Repeated fractional ID vaccination may be an alternative booster vaccination strategy for geriatric populations.

Evaluation of the Safety and Immunogenicity of Fractional Intradermal COVID-19 Vaccines as a Booster: A Pilot Study.

Intradermal vaccination using fractional dosages of the standard vaccine dose is one strategy to improve access to COVID-19 immunization. We conducted a pilot study in healthy adults in Thailand to evaluate the safety and immunogenicity of intradermal administration of fractional doses of ChAdOx1 (1/5th of standard dosage) or BNT162b2 (1/6th of standard dosage) to individuals previously vaccinated (prime) with two-dose intramuscular CoronaVac, ChAdOx1 or BNT162b2. Following an initial immunogenicity exploratory phase for each vaccine combination group (n = 10), a total of 135 participants (n = 45 per group) were recruited to 3 groups (CoronaVac prime-intradermal BNT162b2 boost, CoronaVac prime-intradermal ChAdOx1 boost and ChAdOx1 prime-intradermal BNT162b2 boost) and their immunogenicity data were compared to a previous cohort who received the same vaccine intramuscularly. Two weeks following booster vaccination, neutralizing antibodies against the delta variant were similar between the participants who received intradermal and intramuscular vaccination. However, neutralizing antibodies against the omicron variant in the intradermal BNT162b2 boost groups were ~6-fold lower, while the levels in the ChAdOx1 boost group were similar compared to their respective vaccine regimen given intramuscularly. The intradermal booster significantly increased spike-specific T cell responses in all three groups from pre-booster levels. Local and systemic adverse reactions were milder in intradermal compared to intramuscular injections. Further studies are needed to evaluate the clinical relevance of these findings and the feasibility of administration of intradermal COVID-19 vaccines.

T-Cell Responses Induced by an Intradermal BNT162b2 mRNA Vaccine Booster Following Primary Vaccination with Inactivated SARS-CoV-2 Vaccine.

A practical booster vaccine is urgently needed to control the coronavirus disease (COVID-19) pandemic. We have previously reported the safety and immunogenicity of a fractional intradermal booster, using the BNT162b2 mRNA vaccine in healthy volunteers who had completed two doses of inactivated SARS-CoV-2 vaccine. In this study, an intramuscular booster at full dosage was used as a control, and a half-dose vaccination was included for reciprocal comparison. Detailed T-cell studies are essential to understand cellular responses to vaccination. T-cell immunity was examined using S1 peptide restimulation and flow cytometry. The fractional dose (1:5) of the BNT162b2 mRNA vaccine enhanced antigen-specific effector T-cells, but the responses were less remarkable compared to the intramuscular booster at full dosage. However, the intradermal regimen was not inferior to the intramuscular booster a month after boosting. An intradermal booster using only one-fifth of the standard dosage could provide comparable T-cell responses with the fractional intramuscular booster. This work confirms the efficacy of intradermal and fractional vaccination in terms of T-cell immunogenicity in previously immunised populations.

Immunogenicity and reactogenicity after booster dose with AZD1222 via intradermal route among adult who had received CoronaVac

BackgroundCurrently, booster dose is needed after 2 doses of non-live COVID-19 vaccine. With limited resources and shortage of COVID-19 vaccines, intradermal(ID) administration might be a potential dose-sparing strategy. ObjectiveTo determine immunologic response and reactogenicity of ID ChAdOx1 nCoV-19 vaccine (AZD1222,Oxford/AstraZeneca) as a booster dose after completion of 2-dose CoronaVac(SV) in healthy adult. MethodsThis is a prospective cohort study of adult aged 18–59 years who received 2-dose SV at 14–35 days apart for more than 2 months. Participants received ID AZD1222 at fractional low dose(1×1010 viral particles,0.1 ml). Antibody responses were evaluated by surrogate virus neutralization test(sVNT) against delta variant and wild type, and anti-spike-receptor-binding-domain immunoglobulin G(anti-S-RBD IgG) at prior, day14, 28, 90, and 180 post booster. Solicited reactogenicity was collected for 7 days post-booster. Primary endpoint was the differences of sVNT against delta strain ≥ 80% inhibition at day14 and 90 compared with the parallel cohort study of 0.5-ml intramuscular(IM) route. ResultsFrom August2021, 100 adults with median age of 46 years(IQR 41–52) participated. Prior to booster, geometric mean(GM) of sVNT against delta strain was 22.4% inhibition(95 %CI 18.7–26.9) and of anti-S-RBD IgG was 109.3 BAU/ml(95.4–125.1). Post ID booster, GMs of sVNT against delta strain were 95.5% inhibition (95%CI 94.2–96.8) at day14, 73.1% inhibition (66.7–80.2) at day90, and 22.7% inhibition (14.9–34.6) at day180. The differences of proportion of participants achieving sVNT against delta strain ≥ 80% inhibition in ID recipients versus IM were + 4.2% (95 %CI -2.0to10.5) at day14, and −37.3%(-54.2to-20.3) at day90. Anti-S-RBD IgG GMs were 2037.1 BAU/ml (95%CI 1770.9–2343.2) at day14 and 744.6 BAU/ml(650.1–852.9) at day90, respectively. Geometric mean ratios(GMRs) of anti-S-RBD IgG were 0.99(0.83–1.20) at day14, and 0.82(0.66–1.02) at day90. Only 18% reported feverish, compared with 37% of IM (p = 0.003). Common reactogenicity was erythema at injection site(53%) while 7% reported blister. ConclusionLow-dose ID AZD1222 booster enhanced lower neutralizing antibodies at 3 months compared with IM route. Less systemic reactogenicity occurred, but higher local reactogenicity.

Long-term persistence of antibodies and boostability after rabies intradermal pre-exposure prophylaxis.

Currently, there is limited data on long-term persistence of antibodies and boostability of intradermal (ID) rabies pre-exposure prophylaxis (PrEP) schedules. This study investigated travellers who received a primary ID PrEP schedule at least 5years previously to determine the persistence of antibodies and subsequent antibody response after one 0.1-ml ID booster dose. Adults (age ≥ 18years) who had previously received ID PrEP at a specialist travel medicine clinic in Brisbane, Australia were included. At Day 0, blood was collected for serology and one dose of 0.1-ml ID rabies vaccine (Verorab®) was administered. At Day 7, serology was repeated. At Day 14, participants were given results and enquired if they experienced adverse events following immunization (AEFIs). Antibodies were measured using Platelia Rabies II ELISA; levels ≥0.5 EU/mL were considered antibody-positive. 158 participants were included [64.6% female, median age at enrolment 56.4years, interquartile range (IQR) 42.4-65.2years], and median time since the primary ID PrEP was 8.5years (IQR 6.9-11.7years). The majority of participants (82.3%) were antibody-positive at Day 0. The proportion of participants who were antibody-positive at Day 0 was higher among those who were younger at primary vaccination (87.0% if aged<50years, 75.8% of aged ≥50years). The proportion of participants who were antibody-positive declined as median time since primary vaccination increased, though the trend was not statistically significant (p-trend = 0.187). All except one participant (99.4%) were antibody-positive after one ID booster dose. AEFIs were reported by 42.4% of participants and were mainly mild. Rabies antibodies persist for many years after ID PrEP and can be rapidly boosted with a single ID dose. Future studies are needed to confirm that ID PrEP primes the immune system sufficiently so that boosters are not routinely needed, and only given in the event of a rabies-prone exposure.

Immunogenicity and Safety of an Intradermal BNT162b2 mRNA Vaccine Booster after Two Doses of Inactivated SARS-CoV-2 Vaccine in Healthy Population.

Effective vaccine coverage is urgently needed to tackle the COVID-19 pandemic. Inactivated vaccines have been introduced in many countries for emergency usage, but have only provided limited protection. Heterologous vaccination is a promising strategy to maximise vaccine immunogenicity. Here, we conducted a phase I, randomised control trial to observe the safety and immunogenicity after an intradermal boost, using a fractional dosage (1:5) of BNT162b2 mRNA vaccine in healthy participants in Songkhla, Thailand. In total, 91 volunteers who had been administered with two doses of inactivated SARS-CoV-2 (CoronaVac) were recruited into the study, and then randomised (1:1:1) to received different regimens of the third dose. An intramuscular booster with a full dose of BNT162b2 was included as a conventional control, and a half dose group was included as reciprocal comparator. Both, immediate and delayed adverse events following immunisation (AEFI) were monitored. Humoral and cellular immune responses were examined to observe the booster effects. The intradermal booster provided significantly fewer systemic side effects, from 70% down to 19.4% (p < 0.001); however, they were comparable to local reactions with the conventional intramuscular booster. In the intradermal group after receiving only one fifth of the conventional dosage, serum Anti-RBD IgG was halved compared to the full dose of an intramuscular injection. However, the neutralising function against the Delta strain remained intact. T cell responses were also less effective in the intradermal group compared to the intramuscular booster. Together, the intradermal booster, using a fractional dose of BNT162b2, can reduce systemic reactions and provides a good level and function of antibody responses compared to the conventional booster. This favourable intradermal boosting strategy provides a suitable alternative for vaccines and effective vaccine management to increase the coverage during the vaccine shortage.

A randomized clinical trial to assess the immunogenicity of a single-visit four-dose intradermal booster rabies regimen with topical imiquimod

Background: Two-visit intradermal pre-exposure rabies vaccination schedules (PrEP) are now advised by the WHO. Moreover, a double-dose single-visit intradermal 12ID PrEP schedule showed robust immune responses following four-dose or double-dose single-visit intradermal post-exposure prophylaxis (14ID or 12ID PEP) (Soentjens P et al. Clin Infect Dis Aug 2019). Such accelerated 1-visit schedules for PrEP and PEP at very low cost are very practical. Methods and materials: Aim. To investigate the additional effect of the topical pre-administration of imiquimod (IMIQ) (during 1-visit intradermal PrEP) on the neutralizing antibody responses after a four-dose 1-visit intradermal booster schedule. Methods. Belgian soldiers (N = 268) were vaccinated with a 12ID PrEP schedule and boosted with a 14ID PEP schedule, using the Purified Chicken Embryo Cell Vaccine (PCECV). In this study (EudraCT 2017-002953-12), subjects were randomized (during PrEP) for the topical treatment with IMIQ versus placebo cream, as well as for the use of an intradermal device (VAX-ID™) versus routine intradermal syringe. We investigated the serological responses, by rabies fluorescent focus inhibition test (RFFIT) on day 7, after 14ID PrEP in the four treatment groups for 162 of the 268 subjects. A titer ≥3.0 IU/ml is considered to be a strong and adequate antibody response. Results: Median age was 23.5 (IQR 22.7–24.7). 83% were male. Timing between PrEP and PEP was 1.13 years (IQR 1.13–1.13). The GMT of RFFIT on day 7 after 14ID PEP was 19.42 IU/mL (CI 12.43–30.35). 92.3% of the 52 subjects had a RFFIT ≥0.5 IU/mL at day 7 of which 88,5% a level >3.0 IU/mL and 83% >10.0 IU/mL, following 12ID PrEP. The GMT (2 groups comparison) of RFFIT on day 7 after 14ID by intervention groups was 20.20 (10.58–38.57) and 18.66 (9.63–36.15) for the IMIQ versus placebo group respectively, and 18.09 (8.39–39.00) and 20.84 (12.47–34.85) for the VAX-ID versus needle group respectively. Conclusion: Good anamnestic booster responses following 14ID PEP, one year after 12ID PrEP, were recorded. This powered clinical data, in addition with the data of 12ID PrEP by Soentjens et al., proofs that the concept of single-visit priming and single-visit boosting (PrEP and PEP) is very promising and deserves more promotion.

Evaluation of a one week intradermal regimen for rabies post-exposure prophylaxis: Results of a randomized, open label, active-controlled trial in healthy adult volunteers in India

The currently recommended intradermal regimen for post-exposure prophylaxis spreads over a month period which many times lead to low compliance from the patients. There is a need to introduce and evaluate short course regimens to overcome this problem. This study was conducted to evaluate the immunogenicity and safety of a “new one week intradermal regimen” for rabies post-exposure prophylaxis. A total of 80 healthy adult volunteers were enrolled and allocated randomly either to purified chick embryo cell (PCECV) rabies vaccine or purified verocell rabies vaccine (PVRV), 40 in each group. Each subject received intradermally one of the vaccines, using the one week regimen (4–4-4). Blood samples were collected on Days 0, 7, 14, 28,180 and 365 for estimation of rabies virus neutralizing antibody (RVNA) concentration. The sera samples were analyzed by rapid fluorescent focus inhibition test (RFFIT). All subjects in both the groups had adequate RVNA concentration of ≥ 0.5 IU/mL from day 14 to till day 180 and the difference of geometric mean concentrations between the two groups was not significant (p > 0.606). Further to assess the immunological memory produced by this new regimen, a “single visit four site” intradermal booster vaccination was given to those who did not have adequate RVNA concentration on day 365. This resulted in a quick and enhanced RVNA concentration in these subjects thus denoting a successful anamnestic response. The incidence of adverse events was 8.3% in PCECV group and 1.6% in PVRV group (p = 0.001) and the regimen was well tolerated without any dropouts. In conclusion, the new “one week intradermal regimen” is immunogenic and safe for rabies post-exposure prophylaxis and needs to be further evaluated in persons exposed to rabies.

What are the consequences of having frequent rabies booster vaccinations

Background: Physicians, laboratory scientists, veterinarians and public health officers who have had several potential rabies exposures, are given repeated booster injections often over years. We have experienced that these groups occasionally have a decline in Rabies Neutralizing antibodies (NAbs) when given frequent booster injections. Objective: We compared the dynamics of NAb titers between volunteers following primary vaccination and volunteers who had received repeated booster injections after primary vaccination. Method: We studied subjects who had a previous post-exposure rabies vaccine series and then received an intradermal booster on days 0 and 3. Results: Subjects who had only the primary series and no prior boosters had higher geometric mean NAb titers than those who had received one or more prior boosters. Conclusion: We present hypotheses for this phenomenon and recommend further studies to elucidate mechanisms that might have clinical implications.

Immunogenicity and Safety of an Intradermal Boosting Strategy for Vaccination Against Influenza in Lung Transplant Recipients

The immunogenicity of influenza vaccine is suboptimal in lung transplant recipients. Use of a booster dose and vaccine delivery by the intradermal rather than intramuscular route may improve response. We prospectively evaluated the immunogenicity and safety of a 2-dose boosting strategy of influenza vaccine. Sixty lung transplant recipients received a standard intramuscular injection of the 2006-2007 inactivated influenza vaccine, followed 4 weeks later by an intradermal booster of the same vaccine. Immunogenicity was assessed by measurement of geometric mean titer of antibodies after both the intramuscular injection and the intradermal booster. Vaccine response was defined as 4-fold or higher increase of antibody titers to at least one vaccine antigen. Thirty-eight out of 60 patients (63%) had a response after intramuscular vaccination. Geometric mean titers increased for all three vaccine antigens following the first dose (p < 0.001). However, no significant increases in titer were observed after the booster dose for all three antigens. Among nonresponders, 3/22 (13.6%) additional patients responded after the intradermal booster (p = 0.14). The use of basiliximab was associated with a positive response (p = 0.024). After a single standard dose of influenza vaccine, a booster dose given by intradermal injection did not significantly improve vaccine immunogenicity in lung transplant recipients.

The effectiveness of intradermal pre-exposure rabies vaccination in an Australian travel medicine clinic.

The objective of the study was to assess the effectiveness of intradermal (ID) rabies vaccination and to determine whether any difference in response with age or gender exists. No published Australian data on the subject is available and controversy continues to surround the use of ID rabies vaccination for pre-exposure prophylaxis. Vaccinated travelers requiring postexposure treatment are sometimes considered unvaccinated. By confirming their immunity prior to travel, this problem may be avoided. The data was collected by retrospective analysis over 2 years at a specialized travel medicine clinic in Perth, Western Australia. The standard protocol is three ID injections of 0.1 mL, given on days 0, 7, and 28 with a booster after 12 months. The vaccine used was the Pasteur Merieux human diploid cell vaccine. Serology was performed 3 weeks after completion of the primary course or after a booster. Antibody levels were measured using the rapid fluorescent focus inhibition test, and levels of >0.5 IU/mL were considered protective. A total of 164 travelers were included in the study, of which 144 had completed the three primary ID doses, and 20 had received an ID booster after a previous primary ID course. The mean age was 34.75 years, and gender distribution was equal. The median time between vaccination and serology was 23 days. The antibody levels ranged from 0 to 50 IU/mL with a mean of 8.42 IU/mL. Three travelers had no detectable antibodies giving a seroconversion rate of 98.2%. No statistically significant correlation between age or gender and antibody levels was present. We have found that ID rabies vaccination is effective in a travel clinic with nurses experienced in the technique. The lower cost of ID rabies vaccination makes it accessible to a larger number of travelers. Further studies will be required to determine the duration of protection after ID vaccination and antibody response after postexposure boosters. We will continue to recommend ID rabies vaccination if there is sufficient time for serology to be performed and for results to be available prior to departure.

Three-year experience with 4-site intradermal booster vaccination with rabies vaccine for postexposure prophylaxis.

For booster vaccination of previously immunized persons with potential exposure to rabies, the World Health Organization recommends 2 doses of cell-culture vaccine administered intramuscularly or intradermally on days 0 and 3. We believe that four 0.1-mL intradermal booster doses given on a single day could be used at no risk to the recipient. We studied use of a single booster vaccination on day 0 followed by four 0.1-mL intradermal doses of cell-culture rabies vaccines, and we determined that this is a safe, convenient, and economical regimen for postexposure treatment of previously vaccinated individuals.

Immune response to rabies booster vaccination in subjects who had postexposure treatment more than 5 years previously.

Patients exposed to rabies, who had a history of having received a complete series of intramuscular or intradermal postexposure vaccine treatment 5 or more years previously, all developed an early anamnestic antibody response to two intradermal booster vaccine injections. I t is suggested that such subjects do not require a full five-dose postexposure series nor do they require administration of rabies immune globulin. These data confirm World Health Organization and US-CDC recommendations. Current World Health Organization (WHO) recommendations state that indi&duals,previously vaccinated against rabies with a potent tissue or avian culture vaccine, should be given two tissue or avian culture vaccine boosters on days 0 and 3 ifpostexposure vaccination is required. Boosters can be ahnis te red either intramuscularly as a full ampoule or i n t r a d e r d y as 0.1 mL if the ampoule is reconstituted in 0.5 mL solution or 0.2 mL. if the diluent provided with the vaccine is 1 .O mL.'** Previous studies supported this recommendation.' Investigators at this institution published a study of nerve tissue-derived vaccine recipients, reexposed to rabies up to 50 years after their original immunization, and found that most but not all had an accelerated immune response and thus showed immunological memory. This was not related to the time elapsed since the previous Semple or

Antibody response after a four-site intradermal booster vaccination with cell-culture rabies vaccine.

The current World Health Organization recommendation for booster vaccination of previously immunized individuals with potential exposure to rabies is two doses of vaccine intramuscularly or intradermally on days 0 and 3. We report responses to two types of postexposure treatment of healthy individuals who had received preexposure rabies vaccination 1 year previously. Group A individuals received four intradermal doses (one-fifth of the diluent volume of vaccine per dose) on day 0, and group B individuals received two intramuscular doses on days 0 and 3. Immunogenicity of the two booster regimens was assessed by titrating the amount of neutralizing antibody (Nab). We found that the booster doses of vaccine produced remarkable responses in all subjects. Nab titers of > or = 0.5 IU/mL (acceptable antibody level for protection against rabies) were detected in all subjects on day 14, and they were shown to be consistently high 1 year after the booster vaccination. We also found that the Nab titers for group A were significantly higher (two- to eightfold) than those for group B on days 5, 14, 150, and 360 after the initial booster vaccination (P < .05). Our study shows that the four-site intradermal booster regimen with use of one-fifth of the diluent volume of cell-culture rabies vaccine on day 0 is associated with a significantly higher antibody response than is the conventional booster regimen for subsequent postexposure rabies treatment of individuals who have received preexposure rabies vaccination with cell-culture rabies vaccine 1 year previously.

Mucosal and systemic antibody responses to a C4/V3 construct following DNA vaccination of rabbits via the Peyer's patch.

A plasmid encoding T1-SP10MN(A), a peptide derived from immunodominant regions of human immunodeficiency virus type 1 gp120, was delivered to rabbit Peyer's patches using a helium-driven gene gun. Six weeks thereafter, 2 of 5 animals were given an intradermal booster immunization. Blood, feces, and vaginal washes were collected weekly and assayed by ELISA. High titer T1-SP10MN(A)-specific fecal and vaginal secretory IgA responses were observed, and the response appeared to be augmented following dermal booster immunizations. Specific serum IgG was also detected within 1 week of immunization and remained elevated through week 20 in the 2 animals receiving dermal boosts (titers > or = 6400). This study establishes the Peyer's patch as a promising target tissue for DNA vaccination and demonstrates the efficacy of gene gun-mediated delivery of foreign DNA to a mucosal tissue for the induction of an immune response.

Intradermal hepatitis B vaccination in a 300-bed primary care hospital: Experience with a recombinant vaccine in a four-dose schedule

Background: All hepatitis B vaccination programs, regardless of route, must address such factors as primary response rate, additional booster injections for primary nonresponders, antibody persistence, the need for and timing of additional booster injections for primary responders, overall costs, and medical efficacy. A voluntary intradermal hepatitis B vaccination program with postvaccination testing was implemented in a 300-bed primary care hospital with a recombinant vaccine packaged in a concentration of 20 μg/ml (Engerix B; SmithKline and French Laboratories, Philadelphia, Pa.). Methods: After informed consent was obtained, 460 employees were vaccinated intradermally over the deltoid muscle by a single employee health nurse at months 0 (initial), 1, 2, and 6, followed by testing for serologic response 1 to 2 months after the final dose. Results: Of 411 employees who completed the entire protocol, 90.5% had seroconversion, as determined by enzyme immunoassay. Twelve of 29 primary nonresponders (41%) had seroconversion after an additional (fifth) intradermal booster injection. Of the primary responders, 84.5% remained seropositive when tested 18 months after the initial vaccination injection. These results are comparable to those of intramuscular vaccination and to the original studies of intradermal vaccination with plasma-derived vaccines that had shown excellent immunogenicity. Conclusions: Intradermal and intramuscular hepatitis B vaccination programs must be implemented in somewhat different ways, but both can provide excellent protection against hepatitis B viral infection. Even allowing for the additional expense of postvaccination testing and more frequent booster injections, intradermal vaccination greatly reduces the overall costs of hepatitis B vaccination and may therefore increase compliance in many different settings.

Enhancement of the immune response by intradermal vaccination in cattle with enterotoxigenic Escherichia coli (ETEC) vaccine without adjuvant

A comparison was made of the efficiency of intradermal and subcutaneous routes of vaccination in immunizing cattle with a killed vaccine of Escherichia coli K99+. In this study 135 heifers aged 8-18 months were included. The effect of the number of intradermal injection sites was examined, as well as the optimal time interval between the initial and booster intradermal vaccination. The intradermal route was found to be significantly superior to the subcutaneous route. The optimal time for intradermal booster was approximately 2 weeks. Increasing the number of intradermal injection sites up to 50 (using the same amount of antigen) did not result in an enhancement of the antibody level.

Hepatitis B vaccination in patients infected with Schistosoma mansoni: duration of immunity and immunogenicity of a low dose intradermal booster

Hepatitis B vaccination in patients infected with Schistosoma mansoni: duration of immunity and immunogenicity of a low dose intradermal booster