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2024-2025 BNT162b2 KP.2 COVID-19 full season vaccine effectiveness from vaccine registries linked to administrative claims in two states: A cohort study in non-immunocompromised adults.

BACKGROUND: Data on effectiveness of COVID-19 vaccinations during the 2024-2025 respiratory season are limited, particularly among those with underlying medical conditions (UMC). We estimated BNT162b2 KP.2 vaccine effectiveness (VE) against COVID-19-associated hospital admission, emergency department (ED), and urgent care (UC) visits in two U.S. states. METHODS: Retrospective cohort study of non-immunocompromised adults living in Louisiana or California, with ≥1 year prior continuous enrollment in insurance plans contributing to the HealthVerity claims database beginning August 22, 2024. The effectiveness of BNT162b2 KP.2 vaccine (2024-2025 formulation, hereafter referred to as BNT162b2), measured as a time-varying exposure against hospital admission, ED, or UC encounters with International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) code U07.1 was calculated as 1 - adjusted hazard ratio using Cox proportional hazard models adjusted for age group, sex, state, insurance payor, presence or absence of UMCs, and pre-index healthcare utilization. Stratifications included those aged 65 years and older, those aged 18-64 years with UMCs, and those aged 18-64 years without UMCs. RESULTS: The cohort included 6,256,421 individuals (93% California, 7% Louisiana); 330,565 (5%) received the BNT162b2 vaccine. Vaccinated individuals were older and had more comorbidities, wellness visits, and prior influenza vaccination. Overall, 66% of the study population had ≥1 UMC; the most prevalent conditions were obesity (25%), history of immunocompromised conditions (23%), and mental health conditions (19%). COVID-19-related encounter rates for ED, UC or hospitalization were lower among vaccinated compared to unvaccinated persons (25.1 vs 36.3 per 100,000 person-months). Among all adults, VE was 37% against hospitalization, 12% against ED/UC encounters, and 16% against ED/UC/hospitalization encounters. Results were similar across age groups and UMCs. CONCLUSIONS: BNT162b2 provided protection against COVID-19-associated outcomes of ED, UC or hospitalization among non-immunocompromised U.S. adults, including those with UMCs, over the course of the 2024-2025 respiratory virus season, supporting continued vaccine recommendations. REGISTRATION: This study was posted on clinicaltrials.gov prior to analyses (NCT06923137).

Adolescent

Oral polio vaccine. Effect of booster vaccination one to 14 years after primary series.

We studied the persistence of antibody after vaccination and the response to booster revaccination with trivalent oral polio vaccine (TOPV) administered at varied intervals after the primary series in a large group of children. Decline in antibody was related to intervals since last vaccination, and not to sex, age, age at primary vaccination, or type and number of previous administrations. Geometric mean titers of neutralizing antibody were 11.3 for type 1 and 8.0 for types 2 and 3 poliovirus when vaccine had been given within the previous year, declining to 3.2, 3.0, and 2.1 for types 1, 2, and 3 after nine years. Most children with an initial titer of 4 or less responded to revaccination with a fourfold or greater increase in titer of IgG. Geometric mean titers for all three types of polio dropped to this level when last TOPV administration had been five to six years or more.

Adolescent

Dynamic case-control sampling for rapid estimation of vaccine effectiveness against an emerging infectious disease variant.

New SARS-CoV-2 variants arise frequently with different viral properties that can impact the effectiveness of the vaccines. Updating estimates of vaccine effectiveness (VE) in public health surveillance can be limited by the necessity of conducting a distinct study that entails analysis of prospective cohort data or using a test-negative design. We introduce a method for dynamically updating estimates of VE using data that accumulate in real time. Our method uses dynamic case-control sampling to estimate VE against a newly emerging variant relative to a previous variant. Dynamic case-control sampling is a technique that continuously updates VE estimates by comparing individuals infected with a newly emerging variant (defined as "cases") to those infected with a previously circulating variant (defined as "controls"). We use this estimate in combination with information about VE from the previous variant (these estimates are typically available from larger, traditional studies) to infer VE against the emerging variant. We demonstrate the utility of this method on the BA.1 and BA.2 sub-lineages of the Omicron variant. The method produces estimates of VE comparable to those produced using traditional methods, although with increased SE. The increase in error, however, is reasonable given a much smaller sample size than other studies, and error ranges of the estimates could be significantly improved by sequencing a larger proportion of identified cases. Our method, which assumes only a fraction of the new cases are being sequenced, can be applied by health departments using routinely collected data to produce timely, rigorous VE estimates to rapidly identify potential changes in VE.

Humans

Rotavirus vaccine effectiveness against rotavirus and acute gastroenteritis mortality: an analysis of pooled case-control studies from the MNSSTER-V dataset.

BACKGROUND: Rotavirus accounts for an estimated 25% of diarrhoea deaths in children under 5 years globally, and more than 140 countries have included rotavirus vaccines in their routine national infant vaccination programmes. We aimed to calculate rotavirus vaccine effectiveness against rotavirus-positive and all-cause acute gastroenteritis deaths. METHODS: The Multi-National Subpopulations Study to Evaluate Rotavirus Vaccines (MNSSTER-V) dataset combines child-level data from test-negative case-control studies of rotavirus vaccine effectiveness that enrolled children under 5 years of age seeking care for acute gastroenteritis at hospitals or emergency departments in 24 countries between July 1, 2007, and Aug 24, 2023. Children were included in this study if they were: younger than 5 years, met the acute gastroenteritis case definition (had at least three episodes of diarrhoea in a 24-h period, had non-bloody and non-chronic diarrhoea, and were enrolled within 7 days of diarrhoea onset), met vaccine card quality metrics, had vaccine delivery dates if the child was reported to have received a rotavirus vaccine, and had a reported outcome of death or discharge. In-hospital acute gastroenteritis deaths were characterised, and rotavirus vaccine effectiveness against all-cause and rotavirus-positive acute gastroenteritis mortality was calculated using an unconditional logistic regression model with adjustment for national under-5 mortality strata and child's age. Vaccine effectiveness analyses against all-cause and rotavirus-positive acute gastroenteritis mortality were restricted to children aged at least 3 months who received any routine vaccines from countries reporting at least one acute gastroenteritis death. FINDINGS: From the MNSSTER-V dataset, we included 27 252 children younger than 5 years enrolled from 22 countries; outcomes of patients were not available for two countries. At least one in-hospital acute gastroenteritis death was reported from 16 countries including 21 522 children; in total, 183 all-cause acute gastroenteritis deaths and 25 rotavirus-positive deaths were reported. Among children aged at least 3 months who had received any routine vaccines, receiving at least one dose of a rotavirus vaccine had an adjusted vaccine effectiveness of 75·8% (95% CI 28·4 to 91·8; n=13 630) against rotavirus-positive acute gastroenteritis mortality and 20·8% (-47·0 to 57·3; n=20 005) against all-cause acute gastroenteritis mortality. INTERPRETATION: Rotavirus vaccines are effective in preventing rotavirus-positive acute gastroenteritis mortality. Continued efforts to improve vaccine delivery could help to reduce acute gastroenteritis mortality due to rotavirus worldwide. FUNDING: None.

Humans

Measles vaccination. VIII. The occurrence of antibodies against virus envelope components after immunization with inactivated vaccine. Effects of revaccination with live measles vaccine.

Children immunized with 4 doses of formalin-inactivated vaccine and/or purified hemagglutinin prepared from Tween 80-ether (TE) treated material were subjected to a follow-up 8-9 years after the last dose of vaccine. 11 out of 27 children had clinical and/or serological signs of infections with wild measles virus during the 8 to 9 years post-booster period. 10 out of the 11 children with infections had non-hemagglutinating-inhibiting (HI) hemolysis-inhibiting (HLI) antibodies demonstrable in their sera after removal of HI antibodies by absorption with TE antigen. In contrast 13 out of 16 vaccinees without detectable signs of infection lacked non-HI HLI antibodies. 10 out of these 13 children were vaccinated with further attenuated live measles virus. There were no clinical reactions to faccination. 4 vaccinees with low pre-vaccination HI antibody titers showed significant rises of antibody titers including non-HI HLI antibodies. In the remaining children no take of the live vaccine could be demonstrated. Thus HI antibodies of a certain minimal concentration can block the replication of vaccine virus even in the absence of non-HI HLI antibodies. However, since it will be difficult to establish these conditions by sue of available inactivated vaccines it is recommended that future vaccine products should include both major virus envelope surface components, the hemagglutinin and the hemolysin.

Antibodies, Viral

Influenza vaccine effectiveness in preventing hospitalization for pneumonia in the elderly.

During the winter of 1989-1990, influenza type A(H3N2) circulated widely, causing excess morbidity and mortality nationwide. From November through April, 1989-1990, hospitalized cases of pneumonia and influenza occurring among noninstitutionalized individuals 65 or more years of age were identified by 20 acute care hospitals in southern lower Michigan. These cases were group matched on age, sex, race, and zip code to randomly sampled, community-based controls from a comprehensive listing of Medicare beneficiaries residing in the study area. Self-reported data were collected from cases and controls on influenza vaccine status for the 1989-1990 season and on a number of other factors which could have influenced vaccination status or outcome. Questionnaires were completed by 1,907 individuals, 449 of whom were cases, resulting in an overall response rate of 76%. A community-based influenza surveillance system was implemented to determine the timing and intensity of viral activity and influenza-like illness. Vaccine effectiveness in preventing overall pneumonia and influenza hospitalizations was estimated by logistic regression. During the 3-month period of surveillance-confirmed peak influenza type A(H3N2) circulation, vaccine effectiveness was 45% (95% confidence interval 14-64, p = 0.009). However, during the 3-month period of low or absent virus activity, identical methodology and model specification resulted in an effectiveness estimate of 21% that was not statistically different from zero (p = 0.36). The effectiveness determined during the peak period of virus circulation is felt to be a conservative estimate, since agents other than influenza are responsible for pneumonia and influenza hospitalizations, even during times of peak influenza activity.

Aged

Impediments, imponderables and alternatives in the attempt to develop an effective vaccine against AIDS.

A personal view is presented that current successful vaccines against 'ordinary' viruses do not provide the guidelines needed for development of effective vaccines against the 'extraordinary' viruses that cause AIDS. Present 'candidate' AIDS vaccines fail to recognize the special attributes that are needed to make them successful. There is an urgent need for intensive studies of pathogenesis to seek and find the clues needed for vaccine attack that are at present unknown. Also needed is a targeted Research and Development organization comprising a cadre of capable scientists of requisite disciplines in adequate facilities, dedicated solely to the development of a vaccine against AIDS. The urgency imposed by the AIDS pandemic merits a new dedication to targeted basic research discovery and an effectively concentrated and coordinated applied research initiative.

AIDS Vaccines

Modulation of delayed-type hypersensitivity and cellular immunity to microbial vaccines: effects of cyclophosphamide on the immune response to tularemia vaccine.

Treatment of guinea pigs with cyclophosphamide before immunization with killed tularemia vaccine in Freund incomplete adjuvant produced a prolongation and intensification of delayed-type hypersensitivity and in vitro lymphocyte transformation reactions to tularemia antigen. Such reactions resemble those ordinarily associated with the administration of live tularemia vaccine, killed vaccine in Freund complete adjuvant, or recovery from natural infection. The immunopotentiation lasted longer than that seen previously in other antigenic systems with this drug and was dependent on the dose of vaccine used. More intense delayed skin reactivity could be transferred into normal controls by cells from immunized donors pretreated with cyclophosphamide than by cells from immunized donors that were not pretreated.

Animals

Malaria immunization in Rhesus monkeys. A vaccine effective against both the sexual and asexual stages of Plasmodium knowlesi.

Rhesus monkeys were immunized with a preparation of Plasmodium knowlesi parasites containing principally microgametes with lesser numbers of macrogametes and asexual trophozoites. The antigen mixture was emulsified in Freund's complete adjuvant (FCA) and administered intramuscularly. After one or two inoculations of from 10(5) to 10(7) microgametes in FCA, monkeys showed high levels of circulating anti-gamete antibodies as demonstrated by various in vitro microgamete immobilization or transmission blocking tests. After challenge with P. knowlesi, immunized monkeys developed low level asexual parasitemias and were not infectious to feeding mosquitoes as measured by growth of the parasite on the mosquito gut. Control monkeys developed rapidly rising, usually fatal infections and were highly infectious to mosquitoes. Anti-gamete antibodies appear to neutralize the sexual parasites and prevent mosquito infection within the gut of the recently fed mosquito vector. Suppression of asexual parasitemia in immunized monkeys may be due to the presence of asexual trophozoites in the antigen mixture or to antigens common to both sexual and asexual stages of the parasite. A vaccine effective as a single injection capable of interrupting malaria transmission from man to man whereas reducing the severity of the disease in infected individuals offers a new approach to the control of one of the major diseases affecting man.

Animals

Vaccine effect of intact metacestodes of Taenia crassiceps against T. taeniaeformis infection in rats.

Wistar rats inoculated intraperitoneally with 10 viable metacestodes of Taenia crassiceps without adjuvant once on day 0 showed strong resistance to challenge with 200 eggs of T. taeniaeformis on day 30. When rats were killed one month after challenge, there were 80.4% and 46.1% reductions in the number of cystic and total metacestodes of T. taeniaeformis in the liver, respectively. When five rats were killed 16 months after challenge, they showed almost complete immunity against the challenge, with 99.4% and 91.1% reductions in the number of cystic and total metacestodes, respectively. There were only a few degenerated, pin-point metacestodes of T. taeniaeformis in the liver of all five rats; one harbored one cystic metacestode as well. However, there were no such reductions in rats injected initially with cyst fluid antigens of T. crassiceps with Freund's complete adjuvant. An additional experiment was carried out using 500 eggs of T. taeniaeformis in order to confirm the vaccine effect against higher egg dose. There were 96.6%, 87.9%, 83.9%, and 79.3% reductions in the number of cystic metacestodes in rats initially inoculated with 10 viable, 10 formalized, and 10 frozen metacestodes, and injected with sodium deoxycholate-solubilized metacestode antigens, respectively. It is strongly suggested that rats singly dosed with 10 viable or non-viable, intact metacestodes of T. crassiceps without adjuvant became highly resistant to challenge infection with eggs of T. taeniaeformis, which resulted in almost no cystic metacestode establishment.

Animals

Q-fever soluble vaccine effects in Coxiella burneti sensitized humans.

A Q-fever soluble vaccine (phase I C. burnetitrichloro-acetic acid extract) was administered in a single dose to 28 persons formerly immunized with the same soluble vaccine one year before and to other 28 persons which had naturally been infected with C. burneti one or two years ago. All these persons were skin-tested with the same but diluted vaccine 48 hrs before vaccination. Mild local and general reactions were found only in the C. burneti previously infected vaccinees (local reactions in 9 cases and general reactions in 6 cases). Serological conversion was obtained in 92.8% (complement fixation test) and in 89.3% (mouse protection test) of the previously immunized individuals and in 96.4% (CF test) of the formerly Q-fever infected persons.

Antibodies, Bacterial

[Parotiditis in postvaccination period. Epidemiologic pattern and vaccine effectiveness in an epidemic outbreak].

BACKGROUND: Upon the detection of an excess number of cases of parotiditis in La Almolda (Zaragoza) a descriptive study of the epidemic was carried out with vaccination efficacy being quantified. METHODS: The definition and system of detection of the cases was established. To calculate the rate of infection the available demographic data were used as denominators. A study of retrospective groups was designed to calculate the vaccination efficacy including one group of vaccinated subjects and another of non vaccinated subjects. Age and viral contact were considered as inclusion criteria. RESULTS: Fifty-two cases of parotiditis were detected. The rate of infection in a population of under 30 years of age was 18.9%. The most affected age group corresponded to the interval of between 10-14 years of age with a specific rate of 46.5%. The risk of infection was greatest amongst public school students (RR = 5; p = 0.00015). Vaccination efficacy was 74.68%. CONCLUSIONS: This study confirms the tendency that parotiditis affects older subjects during the prevaccination period. The vaccination efficacy found to be 74.68% was lower the efficacy determined from seroconversion studies.

Adolescent

Effective vaccination against papilloma development by immunization with L1 or L2 structural protein of cottontail rabbit papillomavirus.

Immunization of rabbits with either L1, the major structural protein, or L2, a minor structural protein of cottontail rabbit papillomavirus (CRPV), protected against challenge with the virus. Neutralizing antibodies were elicited by both the L1 and L2 trpE fusion proteins. Neutralization with anti-L1 serum, however, was more efficient than with anti-L2 serum. In contrast, when tested on Western blots the immune response to L2 was stronger than to L1. Rabbits were also protected against CRPV infection by immunization with L1 expressing recombinant vaccinia virus. Sera from two of three rabbits immunized with recombinant vaccinia virus were negative on Western blots but all three were positive in ELISA's with nondenatured fusion protein or in immunoprecipitations. The results suggest that both the viral structural proteins, L1 and L2, merit consideration in the development of a vaccine against papillomavirus.

Animals

Improbability of effective vaccination against human immunodeficiency virus because of its intracellular transmission and rectal portal of entry.

The worldwide effort to produce a vaccine against AIDS continues to disregard the fact that even human immunodeficiency virus (HIV)-specific neutralizing antibodies and cell-mediated immunity are ineffective against virus within cells without viral antigens on the cell membrane--and that much of HIV infection is transmitted in this manner. According to a recent report, a simian immunodeficiency virus vaccine that protected monkeys against an intravenous challenge with cell-free virus was, as predicted, ineffective against an intravenous challenge with the same amount of virus in infected cells. Moreover, antibody and HIV have been found to coexist in cell-free plasma from asymptomatic and symptomatic patients. Excluding direct introduction of HIV into the blood-stream, the most common and efficient form of transmission of HIV infection is by receptive anal intercourse, and semen contains large numbers of infected cells per milliliter. Recent reports showing that colorectal cells can be persistently infected by HIV and that HIV RNA and cDNA are present in the cells of the colon of dead AIDS patients indicate that either cell-free or intracellular HIV has the capacity to multiply at the portal of entry in the colorectal area without interference from neutralizing antibodies. The available data provide no basis for testing any HIV vaccine in human beings either before or after infection. The main challenge is to find a way to kill cells with chromosomally integrated HIV cDNA without harming normal cells, perhaps by identifying repressor proteins that might be produced by the cells with integrated HIV cDNA and thus could become specific targets for cell-killing drugs.

HIV Antibodies