Two-dose Vaccine Regimen Research Articles

Impact of the two-dose rubella vaccination regimen on incidence of rubella seronegativity in gravidae aged 25 years and younger.

ObjectiveThis study compared the incidence of rubella seronegativity among gravidae of 25 year-old and younger, between those born in Hong Kong after 1983 when the two-dose rubella vaccination was implemented, versus gravidae born before, to examine the impact of the two-dose regimen.MethodsIn this retrospective cohort study, the incidence of antenatal rubella seronegativity in our parturients managed in1997-2015 was analysed by their age from ≤16 to 25 years, and the effect of year of birth was determined adjusting for confounding factors including teenage status, obstetric history, anthropometric factors, and health parameters including anaemia, thalassaemia trait and hepatitis B carrier status.ResultsAmong the 12743 gravidae, the 6103 gravidae born after 1983 had overall higher rubella seronegativity (9.1% versus 4.4%, OR 2.061, 95% CI 1.797–2.364), with significant difference (p = 0.006) and inverse correlation (p<0.001) with age, in contrast to the 6640 gravidae born in/before 1983 whom there was significant difference (p = 0.027) but a positive correlation (p = 0.008) with age. For each year of age, the former had significantly higher incidence of rubella seronegativity except for those of ≤16 years. Regression analysis confirmed that birth after 1983 was independently associated with rubella seronegativity (aOR 2.207, 95% CI 1.902–2.562).ConclusionThere was a significant trend between rubella seronegativity with age in young gravidae, but the pattern was opposite between gravidae born after versus in/before 1983, with the former having a higher incidence of seronegativity at all ages. Young women covered by the two-dose rubella immunisation programme have a paradoxically higher incidence of rubella seronegativity.

Current situation of measles in Japan, 2017

A large-scale national measles epidemic occurred among mainly in teenagers and young adults in 2007. MHLW announced ''Special infectious disease prevention guidelines for measles'' (issued on 28 December 2007; Revised issued on 30 March 2013), and Japan decided the elimination target year was fiscal year (FY) 2015. In 2008, it continued to be a large-scale nation epidemic exceeding 10,000 cases, and a large number of 0 to 1 year old infants, teenagers and young adults were suffering. Many cases were unvaccinated, single dose vaccination or unknown vaccination history. The number of measles cases has declined dramatically since 2009, and the measles virus of genotype D5, which was the indigenous strain in Japan, was not detected at the end of May 2010. Regional epidemics were approved in 2011 and 2014, starting from imported cases from overseas, but it ended early. Since 2006, a two-dose routine vaccination regimen of measles rubella combined (MR) vaccine has started, moreover in the 5 years from fiscal 2008, the second dose of MR vaccine for junior high school students and high school students was periodically inoculated and immunization strengthened for teens was done. As a result, antibody positive rate of 95% or more is maintained in all age groups over 2 years old. In March 2015, Japan's measles elimination was certified by the WHO Western Pacific Regional Office. In 2017, outbreaks occurred in adults originating from imported cases from Asia or Europe, but early termination declarations have been made by aggressive measures by local public health centers/institutes. The annual number of reported cases after measles elimination certification is less than 200 cases.

A prospective study on the efficacy of two-dose influenza vaccinations in cancer patients receiving chemotherapy.

Cancer patients receiving chemotherapy are at risk of acquiring influenza infections. Two-dose vaccination is a proposed strategy for increasing vaccination efficacy; however, this has yet to be confirmed in this population. The purpose of this study was to clarify the efficacy and safety of this strategy. We conducted a multicentre prospective study on a two-dose vaccination regimen in cancer patients receiving chemotherapy. Second vaccinations were performed in patients who did not respond to all three viral strains after the first vaccination. Serum haemagglutination inhibition titres were measured to determine the patients' immunological response, 2 weeks prior to the first vaccination, 3-5 weeks after each vaccination, and at the end of the influenza season. We enrolled 109 patients, including 70 with solid tumours, 36 with haematological malignancies, and 3 with both cancer types. Among the total patients, the proportion of patients with protective titres against the three viral strains increased significantly from 3 to 27% (P < 0.01) following vaccination. Among the 79 patients who received a second vaccination, the proportion of those with protective titres against the individual strains increased by 10% (H1N1), 8% (H3N2), and 3% (B) compared with after the first vaccination. Serious adverse events were not observed. We recommend influenza vaccinations for cancer patients, including those receiving chemotherapy. Also, the additional benefit of the second vaccination may be limited.

Using Mobile Health (mHealth) and geospatial mapping technology in a mass campaign for reactive oral cholera vaccination in rural Haiti.

BackgroundIn mass vaccination campaigns, large volumes of data must be managed efficiently and accurately. In a reactive oral cholera vaccination (OCV) campaign in rural Haiti during an ongoing epidemic, we used a mobile health (mHealth) system to manage data on 50,000 participants in two isolated communities.MethodsData were collected using 7-inch tablets. Teams pre-registered and distributed vaccine cards with unique barcodes to vaccine-eligible residents during a census in February 2012. First stored on devices, data were uploaded nightly via Wi-fi to a web-hosted database. During the vaccination campaign between April and June 2012, residents presented their cards at vaccination posts and their barcodes were scanned. Vaccinee data from the census were pre-loaded on tablets to autopopulate the electronic form. Nightly analysis of the day's community coverage informed the following day's vaccination strategy. We generated case-finding reports allowing us to identify those who had not yet been vaccinated.ResultsDuring 40 days of vaccination, we collected approximately 1.9 million pieces of data. A total of 45,417 people received at least one OCV dose; of those, 90.8% were documented to have received 2 doses. Though mHealth required up-front financial investment and training, it reduced the need for paper registries and manual data entry, which would have been costly, time-consuming, and is known to increase error. Using Global Positioning System coordinates, we mapped vaccine posts, population size, and vaccine coverage to understand the reach of the campaign. The hardware and software were usable by high school-educated staff.ConclusionThe use of mHealth technology in an OCV campaign in rural Haiti allowed timely creation of an electronic registry with population-level census data, and a targeted vaccination strategy in a dispersed rural population receiving a two-dose vaccine regimen. The use of mHealth should be strongly considered in mass vaccination campaigns in future initiatives.

A/H5N1 Prepandemic Influenza Vaccine (Whole Virion, Vero Cell-Derived, Inactivated) [Vepacel®

The influenza A subtype H5N1 virus is a likely causative agent for the next human influenza pandemic. Pandemic influenza vaccine production can begin only after a novel pandemic virus emerges. Cell-based vaccine production has advantages over conventional egg-based methods, allowing more rapid large-scale vaccine production. A reliable Vero cell culture system is available for pandemic and prepandemic influenza vaccine production. Prepandemic influenza vaccines are an important component of influenza pandemic preparedness plans, as their targeted use in the pandemic alert period or early in a pandemic is likely to mitigate the consequences of an influenza outbreak. Vepacel® is a prepandemic influenza vaccine (whole virion, Vero cell-derived, inactivated) containing antigen of H5N1 strain A/Vietnam/1203/2004 and is approved for use in the EU. Clinical immunogenicity studies with the vaccine have demonstrated good rates of functional neutralizing antibody responses against the vaccine strain (A/Vietnam/1203/2004), meeting established immunogenicity criteria for seasonal influenza vaccines, and cross-reactivity against H5N1 strains from other clades. In phase I/II and III studies, a heterologous (A/Indonesia/05/2005) booster vaccine administered to healthy adult and elderly volunteers 6-24 months after the two-dose priming vaccine (A/Vietnam/1203/2004) regimen induced good immunogenic responses against both H5N1 strains, demonstrating strong immunological memory. Broadly similar, albeit less robust, responses were observed in two special risk cohorts of immunocompromised and chronically ill patients. In general, adverse events observed in clinical immunogenicity studies with H5N1 vaccine (A/Vietnam/1203/2004) were similar to those reported with non-adjuvanted, inactivated, seasonal influenza vaccines.

Update on Available Vaccines in India: Report of the APPA VU 2010: I

The Asia Pacific Pediatric Association Vaccinology Update 2010 was held in Mumbai on November 13-14, 2010 to discuss the latest information on burden of infectious diseases, recent developments in vaccines and their impact on immunization practices against infectious diseases occurring in Indian children. During the conference the importance of including conjugate Haemophilus influenzae type b vaccine and anti-rabies vaccines in routine immunization was stressed. Also, the need for giving a second dose of measles mumps rubella vaccine at school entry; and the need for a two-dose varicella vaccine regimen (first dose at 12-15 months of age and a second dose at age 4-6 years) was elucidated. Information related to vaccines which have become available in India in recent years, namely, inactivated poliovirus vaccine; diphtheria, tetanus, acellular pertussis (DTaP) vaccine; conjugate pneumococcal vaccine; rotavirus vaccines; H1N1 vaccines; live attenuated hepatitis A virus vaccine; oral cholera vaccine; tetanus, reduced-dose diphtheria, acellular pertussis (Tdap) vaccine; and human papillomavirus vaccines were discussed.

Predicted 30‐year protection after vaccination with an aluminum‐free virosomal hepatitis A vaccine

Few studies have examined the duration of protection following vaccination against hepatitis A virus (HAV) with currently licensed HAV vaccines. This study explored the long-term immunogenicity in individuals vaccinated with the virosomal hepatitis A virus, Epaxal. Adult volunteers (N = 130) previously enrolled into four different studies between 1992 and 1994 and who had completed a 0/12-month immunization regimen (primary and booster dose) were asked to participate in this follow-up study. Yearly anti-HAV titers up to 6 years following booster vaccination, and then once 9-11 years after booster were measured using two assays, Enzygnost and AxSYM HAVAB 2.0. Based on the Enzygnost assay, the seroprotection rate 9-11 years after booster was 100%, with a geometric mean concentration (GMC) of anti-HAV antibodies of 526 mIU/ml. Females had markedly higher GMCs than males (741 mIU/ml vs. 332 mIU/ml). Using an anti-HAV cut-off titer of >or=10 mIU/ml, a linear mixed mathematical model predicted a median duration of protection of 52.1 years. A duration of protection >or= 35.7 years was predicted for 95% of subjects. A more stringent cut-off of >or=20 mIU/ml shortened the median predicted duration of protection to 45.0 years. In conclusion, a two-dose Epaxal vaccination regimen confers in healthy adults a real-time protection of at least 9-11 years; this protection is predicted to last at least 30 years in over 95% of individuals. Further studies are necessary to assess the real duration of seroprotection and whether an additional booster is necessary later.

Strategies for mitigating an influenza pandemic with pre-pandemic H5N1 vaccines

The recent worldwide spread of the swine-origin H1N1 2009 influenza outbreak has resulted in its designation as a pandemic by the World Health Organization. While it appears to result in mild symptoms, concern still exists that a more severe influenza pandemic with a high case fatality ratio might arise by reassortment or mutation of the currently circulating avian influenza (H5N1) virus. Given that recently developed candidate pre-pandemic H5N1 vaccines have shown potential for cross-strain protection, we investigated alternative vaccination strategies that exploit such vaccines using an agent-based simulation model of an actual community of approximately 30 000 people in a developed country. Assuming that a two-dose vaccination regimen would be required, we examined three vaccination strategies: pre-emptive, with vaccination applied prior to emergence of human-transmissible H5N1 influenza; reactive, where vaccination was initiated immediately after the first cases in the community were diagnosed; and a 'split' strategy where the first dose was administered pre-emptively during the pre-pandemic phase, with the second dose administered reactively. We showed that by effectively moving the delay between first and second doses into the pre-pandemic period, the split vaccination strategy achieved a substantially better attack rate reduction than the reactive strategy. Our results for an influenza strain with a reproduction number of 1.5 suggest reactive vaccination strategies that may be applicable to the current H1N1 2009 pandemic.

A Randomized Longitudinal Trial to Test the Effect of Regional Vaccination Within a Cattle Feedyard on Escherichia coli O157:H7 Rectal Colonization, Fecal Shedding, and Hide Contamination

We tested the efficacy of vaccinating all cattle within a region of a cattle feedlot using a two-dose regimen of a vaccine against type III secreted proteins of Escherichia coli O157:H7. Cattle (n = 504) were randomly assigned to 63 pens (8 steers/pen) within 3 treatment regions of the feedyard. All pens within each region were assigned: (1) two doses of vaccine (ALLVAC), (2) two doses of adjuvant as placebo (NOVAC), or (3) commingled vaccination (HALFVAC), four of eight cattle in each pen receiving two doses of vaccine, and the others adjuvant. Binary outcomes were (1) fecal shedding of E. coli O157:H7 42, 63, and 84 days postvaccination (dpv), (2) hide contamination 42, 63, and 84 dpv, and at the abattoir 85 dpv, and (3) colonization of the terminal rectal mucosa at the abattoir 85 dpv. For each outcome, multilevel logistic regression tested the effect of regional vaccination (ALLVAC vs. NOVAC), and compared commingled vaccinated versus placebo-treated cattle within HALFVAC pens. For fecal shedding, regional vaccine efficacy of ALLVAC compared to NOVAC pens was 63% (OR = 0.34, p = 0.0009), similar to vaccine efficacy of 52% for vaccinated cattle compared to placebo-treated cattle within HALFVAC pens (OR = 0.48, p = 0.014). For hide contamination, vaccine efficacy was 55% for regional vaccination of cattle in ALLVAC pens compared to NOVAC pens (OR = 0.43, p = 0.014). However, commingling vaccinated and placebo-treated cattle was not protective of hide contamination (OR = 0.67, p = 0.33). Colonization of cattle at the abattoir was not different among vaccinated and placebo-treated cattle (p = 0.63). We concluded that the two-dose vaccine regimen effectively reduced E. coli O157:H7 fecal shedding and hide contamination, and that vaccination of cattle within regions of the feedyard provided greater protection against hide contamination than commingling vaccinates and nonvaccinates.

A Two-Dose Regimen of a Vaccine Against Type III Secreted Proteins ReducedEscherichia coliO157:H7 Colonization of the Terminal Rectum in Beef Cattle in Commercial Feedlots

A large-scale clinical vaccine trial of commercially fed cattle was conducted to test the efficacy of a two-dose regimen of a vaccine product against type III secreted proteins of enterohemorrhagic Escherichia coli O157:H7 on the probability to detect the same organism from terminal rectal mucosa (TRM) as a measure of gut colonization. Vaccine was administered to all cattle within treated pens at arrival processing and at reimplant processing. At harvest, TRM was collected from a sample of cattle from within vaccinated and nonvaccinated pens. The TRM were collected by scraping the mucosa of the terminal rectum 3-5 cm proximal to the rectoanal juncture. E. coli O157:H7 was isolated and identified from TRM using standard culture methods involving selective enrichment, immunomagnetic separation, and PCR confirmation. The probability to detect E. coli O157:H7 from TRM was modeled using a generalized linear mixed model with a logit link function and accounting for random effects of pen within feedlot. Seven hundred eighteen cattle were tested from within 21 pens of cattle (11 vaccinated and 10 not vaccinated) representing 3683 cattle. E. coli O157:H7 was cultured from 68 of 718 (9.5%) TRM samples. Eleven of 382 (2.9%) vaccinated cattle and 57 of 336 (17.0%) nonvaccinated cattle were TRM culture positive. From the multilevel logistic model, vaccinated cattle were 92% less likely to be colonized with E. coli O157:H7 than nonvaccinated cattle (odds ratio [OR] = 0.07, p = 0.0008). Additional explanatory variables were region of the state (OR = 7.4, p = 0.04), and pens with fewer cattle (OR = 0.22, p = 0.05). We concluded that the two-dose vaccine regimen effectively reduced the probability for E. coli O157:H7 colonization of the terminal rectum of commercially fed cattle at harvest.

A Two-Dose Regimen of a Vaccine AgainstEscherichia coliO157:H7 Type III Secreted Proteins Reduced Environmental Transmission of the Agent in a Large-Scale Commercial Beef Feedlot Clinical Trial

A clinical vaccine trial of commercially fed cattle tested the effect of a two-dose regimen of a vaccine product against type III secreted proteins of enterohemorrhagic Escherichia coli O157:H7 on the probability of detecting the organism on environmental sampling devices. Within commercial feedlots, pens of vaccinated and unvaccinated cattle were matched by reprocessing schedule and time of sampling. Vaccine was administered to all cattle within treated pens at arrival processing and again at re-implant processing. Pens of cattle were sampled 1 week after the second dose of vaccine and every 3 weeks for four test periods. Pair-matched pens of cattle were sampled concurrently. Test samples were seven ropes per pen hung overnight from the feed-bunk neck-rail (ROPES). Recovery of E. coli O157:H7 from at least one rope classified pens ROPES-positive. E. coli O157:H7 isolates were identified by standard biochemical methods and multiplex polymerase chain reaction. The probability for pens of cattle to test ROPES-positive was modeled using multilevel logistic regression with variance adjustment for clustering by matched pens and repeated measures. We studied 140 pens of cattle representing 20,556 cattle in 19 feedlots February through October 2004. Vaccinated pens of cattle were less likely to test ROPES-positive (OR = 0.59, p = 0.004). Because ROPES testing identifies organisms in the mouth of cattle, and the outcome is both associated with presence of the organism in the pen environment and correlated with the prevalence of fecal shedding, we conclude the two-dose vaccine regimen reduces the probability for environmental transmission of E. coli O157:H7 within commercial cattle feeding systems.

Reply

We agree with Dr. Tabor that our findings1 cannot be extrapolated to recipients of other hepatitis B (HB) vaccines, and hence more data are needed to issue a recommendation of routine booster vaccination for recombinant HB vaccine recipients. Although a qualitative difference does exist between plasma-derived and genetically engineered HB vaccine, the durability of antibodies produced by them may not differ from each other. Studies to understand long-term outcome of recipients of recombinant HB vaccine are the priority data that we need. We also appreciate the comments by Dr. Chan and colleagues on our report. HB vaccine is indeed a reliable vaccine that has prevented chronic infections in most of vaccinees. Many previous reports, including one by ourselves2 showed a routine booster vaccination may not be required to provide protection against chronic HB virus infection before age 15 years. However, most of the studies were confined to subjects in early ages of life. The real threat may emerge when the vaccinated subjects become older and begin to both engage in sexual activity and get along with older generations who still have a high HB surface antigen (HBSAg) carrier rate. Encouragement of safe sex, of course, is certainly an option in preventing not only HB infection but also other sexually transmitted diseases. However, if safe sex practice could be easily executed, diseases such as AIDS would not spread so rampantly. Maintaining and prolonging the protection by vaccination may be a more reliable choice. Nevertheless, we agree that cost-effectiveness analyses are needed. Our data1 showed that 2.7% of children whose postvaccination anti-HBs had been documented did not respond to one dose of HB vaccine booster at the age of 15 years. Besides, a blunted serological response was noted in approximately 20% of the patients. Furthermore, a breakthrough infection was found in a child whose anti-HBs had been documented after primary immunization and persisted to age 7 years. All the findings imply the immune memory, either humoral or cellular immunity, has waned significantly. A booster dose given prior to age 15 years or a two-dose HB vaccine regimen would have been needed for the children to maintain a protective level of antibody. Although Dr. Chan stated the percentage of patients that became HBsAg-positive was low (1/26, 4%), we are concerned with the possibility that this number will increase as the immune memory continues to decay and due to any possible increased risk of exposure in life after the teenage years. Generally speaking, a booster dose is needed to maintain the protection conferred by a killed vaccine. From the perspective of public health, if a booster vaccination program is to be implemented, it is imperative to set booster vaccination at an age when all the children are still easily accessible and one-dose regimen is universally effective in inducing a protective antibody. Although we are not yet ready to recommend routine booster vaccination for all HB vaccines, our study on plasma-derived vaccine provided an important observation that for sure will invite more elegant studies to elucidate this issue. Chun-Yi Lu*, Yen-Hsuan Ni*, Mei-Hwei Chang*, Chin-Yun Lee*, Li-Min Huang*, * Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.

Protective killed Leptospira borgpetersenii vaccine induces potent Th1 immunity comprising responses by CD4 and gammadelta T lymphocytes.

Leptospira borgpetersenii serovar hardjo is the most common cause of bovine leptospirosis and also causes zoonotic infections of humans. A protective killed vaccine against serovar hardjo was shown to induce strong antigen-specific proliferative responses by peripheral blood mononuclear cells (PBMC) from vaccinated cattle by 2 months after the first dose of vaccine. This response was absent from nonvaccinated control cattle. The mean response peaked by 2 months after completion of the two-dose vaccination regimen, and substantial proliferation was measured in in vitro cultures throughout the 7 months of the study period. Variations in magnitude of the response occurred among the vaccinated animals, but by 7 months postvaccination there was a substantial antigen-specific response with PBMC from all vaccinated animals. Up to one-third of the PBMC from vaccinated animals produced gamma interferon (IFN-gamma) after 7 days in culture with antigen, as ascertained by flow cytometric analysis, and significant levels of IFN-gamma were measured in culture supernatants by enzyme-linked immunosorbent assay. Two-color immunofluorescence revealed that one-third of the IFN-gamma-producing cells were gammadelta T cells, with the remaining cells being CD4(+) T cells. The significance of this study is the very potent Th1-type immune response induced and sustained following vaccination with a killed bacterial vaccine adjuvanted with aluminum hydroxide and the involvement of gammadelta T cells in the response. Moreover, induction of this Th1-type cellular immune response is associated with the protection afforded by the bovine leptospiral vaccine against L. borgpetersenii serovar hardjo.

Efficacy of influenza vaccination in adult liver transplant recipients

To assess the efficacy of influenza vaccination in immunocompromised adult liver transplant (LTx) recipients, the serum antibody responses of 61 of these patients and 35 liver cirrhosis patients with those of 45 of their healthy spouses were compared, after one and two vaccinations with a commercial trivalent subunit influenza vaccine. In addition, virus-specific proliferative T-cell responses were measured in LTx recipients and their healthy spouses. In all three study groups, significant rises in geometric mean antibody titers were observed for all three antigens after one vaccination. These titers did not continue to increase significantly after the second vaccination in patients with cirrhosis and control subjects but did rise for LTx recipients. The overall antibody response to all three influenza virus strains proved to be significantly lower in the LTx recipients than in the group of healthy subjects after both one and two vaccinations. More than 68% of the LTx recipients developed hemagglutination-inhibiting serum antibody titers >/=40 against all three vaccine strains after the first vaccination and more than 80% after the second vaccination. These findings correlated with the T-cell responses determined for the group of LTx recipients and healthy control individuals. Testing of the respective serum samples against influenza virus A/Sydney/5/97, which circulated in the 1997-1998 influenza season and showed a considerable mismatch with the vaccine strain A/Nanchang/933/95, indicated that such a mismatch may have significant consequences for vaccine efficacy, especially for LTx recipients. Collectively the data show that LTx recipients can be vaccinated effectively against influenza despite immunosuppressive therapy. A two-dose vaccination regimen improved vaccination efficacy in LTx recipients. Whether transplant patients generally benefit from a two-dose vaccination regimen should be evaluated further.

Field trial of a locally produced, killed, oral cholera vaccine in Vietnam

Several studies have shown that orally administered killed cholera vaccines are safe and protective in populations at risk of cholera in developing countries. However, these vaccines have not been adopted for use in developing countries because of their expense and limited efficacy in young children. We have tested an inexpensive, killed whole-cell cholera vaccine developed and produced in Vietnam. The efficacy of the vaccine was assessed in a large-scale, open field trial in people at least 1 year old residing in 22,653 households in the central coastal city of Hue. Alternate households were assigned vaccine (67,395 people; two doses per person) or no vaccine (67,058 people). Surveillance for cholera was conducted in all Ministry of Health facilities serving this population. Analysis was by intention to treat. During an outbreak of El Tor cholera 8-10 months after vaccination, 37 cases of cholera requiring inpatient care occurred among age-eligible people allocated to the vaccine group, and 92 cases among age-eligible people allocated to the no-vaccine group (protective impact 60% [95% CI 40-73]). Among the 51,975 people who received the complete two-dose vaccine regimen, the protective efficacy was 66% (46-79): in this subset, the protective efficacy was similar for children aged 1-5 years (68%) and for older people (66%). These findings suggest that oral killed whole-cell vaccines can confer substantial protection against El Tor cholera in young children, who are at highest risk of cholera in endemic settings. An inexpensive, locally produced, and effective oral cholera vaccine may be within reach of the limited health-care budgets of poor countries with endemic cholera, if our findings can be replicated in a randomised double-blind trial.

Testing for Antibody to Hepatitis A to Decrease the Cost of Hepatitis A Prophylaxis With Immune Globulin or Hepatitis A Vaccines

The introduction of new vaccines to prevent hepatitis A infection raises the question of the cost of these vaccines relative to immune globulin when short-term protection against hepatitis A is required. Since the prevalence of hepatitis A antibodies (anti-HAV) in the US population increases rapidly with age, testing for anti-HAV may decrease the cost of vaccination programs. A cost-analysis model was developed that incorporates the cost of immune globulin or hepatitis A vaccine, the number of doses of vaccine, the cost of testing for anti-HAV in either commercial or public-sector laboratories, and the prevalence of anti-HAV in the general population by age. In comparison with hepatitis A vaccines, with expected costs between $10 and $25 per dose, use of immune globulin for postexposure prophylaxis or preexposure short-term (< or = 6 months) prophylaxis is much less expensive for all age groups. Testing for anti-HAV does not significantly diminish the cost of immune globulin regimens. In contrast, if anti-HAV testing is performed in a public-sector laboratory at $10 per test, and hepatitis A vaccine costs $10 per dose, testing reduces vaccination costs in those 40 years of age or older for a two-dose vaccine regimen and in those 30 years of age or older for a three-dose regimen. At the other end of the spectrum, if vaccine costs $35 per dose, commercial testing for anti-HAV at $25 per person reduces the costs in those 30 years of age or older if either a two- or three-dose regimen is elected. However, vaccine savings are realized in those 10 years and older if public-sector testing is performed and three doses of vaccine at $35 per dose are utilized. In an intermediate scenario of public-sector testing and vaccines costing $25 per dose, the cost would also be reduced in those 30 years old or older. Testing for anti-HAV in frequent travelers, international government, business, and volunteer workers, military personnel, etc, may be an effective means of decreasing costs of hepatitis A prevention.

Formulation of inactivated influenza vaccines for providing effective cross-protection by intranasal vaccination in mice

Attempts were made to formulate an inactivated influenza vaccine to provide effective cross-protection by intranasal vaccination in mice. Mice were immunized with a nasal site-restricted volume of various HA vaccines (split-product virus vaccines), prepared from some of the H1N1 subtype viruses which circulated in humans from 1934 to 1986, together with cholera toxin B subunit (CTB) as an adjuvant. Four weeks later, they were challenged intranasally with a lethal dose of the earliest H1N1 virus strain, A/PR/8/34 (PR8) or the latest virus strain, A/Yamagata/120/86 (Yamagata/86). The adjuvant-combined vaccines, prepared from drift H1N1 viruses, A/Kumamoto/37/79 and A/Bangkok/10/83, provided a higher degree of cross-protection against a challenge with Yamagata/86 than with PR8. A booster with another drift virus vaccine given 4 weeks after the primary vaccination increased the protection against Yamagata/86; the effect was higher when mice were vaccinated with a later strain as the second antigen than when boosted with PR8. These results suggest that vaccination with a later virus strain followed by another later strain in a two-dose nasal vaccination regimen gives effective cross-protection against the current epidemic virus strains.

Antibody response to a two-dose influenza vaccine regimen in adult lymphoma patients on chemotherapy.

A study was conducted to determine if a two-dose regimen of influenza vaccine would enhance the immunologic response of 41 patients with lymphoma receiving chemotherapy. Hemagglutinin-inhibiting antibody responses to influenza A/H1N1, A/H3N2 and B virus occurred in 32%, 24% and 20% of patients following one dose, and in 49%, 41% and 46% of patients following two doses, respectively. Responses to one or more vaccine components occurred in 42% of patients after one dose and in 71% after two doses. Fifty percent of the patients who did not respond after one dose responded after two doses. A two-dose regimen of influenza immunization may significantly enhance the response rate of cancer patients receiving chemotherapy.

Vaccination to protect calves against infectious bovine rhinotracheitis.

A commercially available inactivated vaccine against infectious bovine rhinotracheitis (BHV1) was tested to assess its ability to immunise young seronegative calves and protect them against challenge with a virulent strain of BHV1. Calves showed seroconversion after one or two doses of vaccine. A two-dose and three-dose vaccination regimen each afforded calves significant protection against challenge as judged by the development of clinical symptoms. Vaccinated calves were on average 7 to 10 kg heavier than control calves 24 days after challenge, a statistically significant difference. Vaccination had no significant effect on the virus excretion pattern after challenge.