Hubbry Logo
Passive immunityPassive immunityMain
Open search
Passive immunity
Community hub
Passive immunity
logo
7 pages, 0 posts
0 subscribers
Be the first to start a discussion here.
Be the first to start a discussion here.
Passive immunity
Passive immunity
Passive immunity
View on Wikipedia
from Wikipedia

In immunology, passive immunity is the transfer of active humoral immunity of ready-made antibodies. Passive immunity can occur naturally, when maternal antibodies are transferred to the fetus through the placenta, and it can also be induced artificially, when high levels of antibodies specific to a pathogen or toxin (obtained from humans, horses, or other animals) are transferred to non-immune persons through blood products that contain antibodies, such as in immunoglobulin therapy or antiserum therapy.[1] Passive immunization is used when there is a high risk of infection and insufficient time for the body to develop its own immune response, or to reduce the symptoms of ongoing or immunosuppressive diseases.[2] Passive immunization can be provided when people cannot synthesize antibodies, and when they have been exposed to a disease that they do not have immunity against.[3]

Naturally acquired

[edit]

Maternal passive immunity

[edit]

Maternal passive immunity is a type of naturally acquired passive immunity, and refers to antibody-mediated immunity conveyed to a fetus or infant by its mother. Naturally acquired passive immunity can be provided during pregnancy, and through breastfeeding.[4] In humans, maternal antibodies (MatAb) are passed through the placenta to the fetus by an FcRn receptor on placental cells. This occurs predominately during the third trimester of pregnancy, and thus is often reduced in babies born prematurely. Immunoglobulin G (IgG) is the only antibody isotype that can pass through the human placenta, and is the most common antibody of the five types of antibodies found in the body. IgG antibodies protects against bacterial and viral infections in fetuses. Immunization is often required shortly following birth to prevent diseases in newborns such as tuberculosis, hepatitis B, polio, and pertussis, however, maternal IgG can inhibit the induction of protective vaccine responses throughout the first year of life. This effect is usually overcome by secondary responses to booster immunization.[5] Maternal antibodies protect against some diseases, such as measles, rubella, and tetanus, more effectively than against others, such as polio and pertussis.[6] Maternal passive immunity offers immediate protection, though protection mediated by maternal IgG typically only lasts up to a year.[6]

Passive immunity is also provided through colostrum and breast milk, which contain IgA antibodies that are transferred to the gut of the infant, providing local protection against disease causing bacteria and viruses until the newborn can synthesize its own antibodies.[7] Protection mediated by IgA is dependent on the length of time that an infant is breastfed, which is one of the reasons the World Health Organization recommends breastfeeding for at least the first two years of life.[8]

Other species besides humans transfer maternal antibodies before birth, including primates and lagomorphs (which includes rabbits and hares).[9] In some of these species IgM can be transferred across the placenta as well as IgG. All other mammalian species predominantly or solely transfer maternal antibodies after birth through milk. In these species, the neonatal gut is able to absorb IgG for hours to days after birth. However, after a period of time the neonate can no longer absorb maternal IgG through their gut, an event that is referred to as "gut closure". If a neonatal animal does not receive adequate amounts of colostrum prior to gut closure, it does not have a sufficient amount of maternal IgG in its blood to fight off common diseases. This condition is referred to as failure of passive transfer. It can be diagnosed by measuring the amount of IgG in a newborn's blood, and is treated with intravenous administration of immunoglobulins. If not treated, it can be fatal.[citation needed]

Other

[edit]

A preprint suggested that (SARS-CoV-2) antibodies in or transmitted through the air are an unrecognized mechanism by which, transferred, passive immune protection occurs.[10][better source needed]

Antibodies from vaccination can be present in saliva and thereby may have utility in preventing infection.[11][better source needed]

Artificially acquired

[edit]
See also: Temporarily induced immunity

Artificially acquired passive immunity is a short-term immunization achieved by the transfer of antibodies, which can be administered in several forms; as human or animal blood plasma or serum, as pooled human immunoglobulin for intravenous (IVIG) or intramuscular (IG) use, as high-titer human IVIG or IG from immunized donors or from donors recovering from the disease, and as monoclonal antibodies (MAb). Passive transfer is used to prevent disease or used prophylactically in the case of immunodeficiency diseases, such as hypogammaglobulinemia.[12][13] It is also used in the treatment of several types of acute infection, and to treat poisoning.[2] Immunity derived from passive immunization lasts for a few weeks to three to four months.[14][15] There is also a potential risk for hypersensitivity reactions, and serum sickness, especially from gamma globulin of non-human origin.[7] Passive immunity provides immediate protection, but the body does not develop memory; therefore, the patient is at risk of being infected by the same pathogen later unless they acquire active immunity or vaccination.[7]

History and applications of artificial passive immunity

[edit]
A vial of diphtheria antitoxin, dated 1895

In 1888 Emile Roux and Alexandre Yersin showed that the clinical effects of diphtheria were caused by diphtheria toxin and, following the 1890 discovery of an antitoxin-based immunity to diphtheria and tetanus by Emil Adolf von Behring and Kitasato Shibasaburō, antitoxin became the first major success of modern therapeutic immunology.[16][17] Shibasaburo and von Behring immunized guinea pigs with the blood products from animals that had recovered from diphtheria and realized that the same process of heat treating blood products of other animals could treat humans with diphtheria.[18] By 1896, the introduction of diphtheria antitoxin was hailed as "the most important advance of the [19th] Century in the medical treatment of acute infective disease".[19]

Prior to the advent of vaccines and antibiotics, specific antitoxin was often the only treatment available for infections such as diphtheria and tetanus. Immunoglobulin therapy continued to be a first line therapy in the treatment of severe respiratory diseases until the 1930s, even after sulfonamides were introduced.[13]

This image is from the Historical Medical Library of The College of Physicians of Philadelphia. This displays the administration of diphtheria antitoxin from horse serum to young child, dated 1895.

In 1890 antibody therapy was used to treat tetanus, when serum from immunized horses was injected into patients with severe tetanus in an attempt to neutralize the tetanus toxin, and prevent the dissemination of the disease. Since the 1960s, human tetanus immune globulin (TIG) has been used in the United States in unimmunized, vaccine-naive or incompletely immunized patients who have sustained wounds consistent with the development of tetanus.[13] The administration of horse antitoxin remains the only specific pharmacologic treatment available for botulism.[20] Antitoxin also known as heterologous hyperimmune serum is often also given prophylactically to individuals known to have ingested contaminated food.[6] IVIG treatment was also used successfully to treat several patients with toxic shock syndrome, during the 1970s tampon scare.[citation needed]

Antibody therapy is also used to treat viral infections. In 1945, hepatitis A infections, epidemic in summer camps, were successfully prevented by immunoglobulin treatment. Similarly, hepatitis B immune globulin (HBIG) effectively prevents hepatitis B infection. Antibody prophylaxis of both hepatitis A and B has largely been supplanted by the introduction of vaccines; however, it is still indicated following exposure and prior to travel to areas of endemic infection.[21]

In 1953, human vaccinia immunoglobulin (VIG) was used to prevent the spread of smallpox during an outbreak in Madras, India, and continues to be used to treat complications arising from smallpox vaccination. Although the prevention of measles is typically induced through vaccination, it is often treated immuno-prophylactically upon exposure. Prevention of rabies infection still requires the use of both vaccine and immunoglobulin treatments.[13]

During a 1995 Ebola virus outbreak in the Democratic Republic of Congo, whole blood from recovering patients, and containing anti-Ebola antibodies, was used to treat eight patients, as there was no effective means of prevention, though a treatment was discovered recently in the 2013 Ebola epidemic in Africa. Only one of the eight infected patients died, compared to a typical 80% Ebola mortality, which suggested that antibody treatment may contribute to survival.[22] Immune globulin or immunoglobulin has been used to both prevent and treat reactivation of the herpes simplex virus (HSV), varicella zoster virus, Epstein-Barr virus (EBV), and cytomegalovirus (CMV).[13]

FDA licensed immunoglobulins

[edit]

The following immunoglobulins are the immunoglobulins currently approved for use for infectious disease prophylaxis and immunotherapy, in the United States.[23]

FDA approved products for passive immunization and immunotherapy
Disease Product[a] Source Use
Botulism Specific equine IgG horse Treatment of wound and food borne forms of botulism.
Despeciated equine IgG[24]
Human specific IgG[24] human Treatment of infant botulism types A and B; brand name "BabyBIG".
Cytomegalovirus (CMV) hyperimmune IVIG human Prophylaxis, used most often in kidney transplant patients.
Diphtheria Specific equine IgG horse Treatment of diphtheria infection.
Hepatitis B Hepatitis B Ig human Post-exposure prophylaxis, prevention in high-risk infants
(administered with Hepatitis B vaccine).
Hepatitis A, measles Pooled human Ig human serum Prevention of Hepatitis A and measles infection,
treatment of congenital or acquired immunodeficiency.
ITP, Kawasaki disease,
IgG deficiency		 Pooled human IgG human serum Treatment of ITP and Kawasaki disease,
prevention/treatment of opportunistic infection with IgG deficiency.
Rabies Rabies Ig human Post-exposure prophylaxis (administered with rabies vaccine).
Tetanus Tetanus Ig human Treatment of tetanus infection.
Vaccinia Vaccinia Ig human Treatment of progressive vaccinia infection
including eczema and ocular forms (usually resulting from
smallpox vaccination in immunocompromised individuals).
Varicella (chicken-pox) Varicella-zoster Ig human Post-exposure prophylaxis in high risk individuals.
Rh disease Rho(D) immune globulin human Prevention of RhD isoimmunization in Rh(D)-negative mothers[25]
  1. ^ Specific or not noted: hyperimmune globulin or antitoxin. Pooled: mixed Ig from ordinary sources, also known as normal human immunoglobulin.

Passive transfer of cell-mediated immunity

[edit]

The one exception to passive humoral immunity is the passive transfer of cell-mediated immunity, also called adoptive immunization which involves the transfer of mature circulating lymphocytes. It is rarely used in humans, and requires histocompatible (matched) donors, which are often difficult to find, and carries severe risks of graft-versus-host disease.[2] This technique has been used in humans to treat certain diseases including some types of cancer and immunodeficiency. However, this specialized form of passive immunity is most often used in a laboratory setting in the field of immunology, to transfer immunity between "congenic", or deliberately inbred mouse strains which are histocompatible.[citation needed]

Advantages and disadvantages

[edit]

Passive immunity starts working faster than vaccines do, as the patient's immune system does not need to make its own antibodies: B cells take time to activate and multiply after a vaccine is given. Passive immunity works even if an individual has a immune system disorder that prevents them from making antibodies in response to a vaccine.[18] In addition to conferring passive immunities, breastfeeding has other lasting beneficial effects on the baby's health, such as decreased risk of allergies and obesity.[26]

A disadvantage to passive immunity is that producing antibodies in a laboratory is expensive and difficult to do. In order to produce antibodies for infectious diseases, there is a need for possibly thousands of human donors to donate blood or immune animals' blood would be obtained for the antibodies. Patients who are immunized with the antibodies from animals may develop serum sickness due to the proteins from the immune animal and develop serious allergic reactions.[6] Antibody treatments can be time-consuming and are given through an intravenous injection or IV, while a vaccine shot or jab is less time-consuming and has less risk of complication than an antibody treatment. Passive immunity is effective, but only lasts a short amount of time.[18]

See also

[edit]

References

[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Passive immunity

View on Grokipedia
from Grokipedia
Passive immunity is a form of adaptive immunity in which pre-formed antibodies are transferred to an individual from another source, providing immediate but temporary protection against specific pathogens or toxins without activating the recipient's own to produce antibodies. This contrasts with active immunity, where the body generates its own long-lasting through exposure to antigens. Passive immunity typically lasts only a few weeks to several months, as the transferred antibodies are eventually degraded without replenishment. Passive immunity occurs naturally when maternal antibodies, primarily (IgG), cross the to protect the during , or when secretory (IgA) is provided through and to safeguard the infant's . These maternal antibodies can offer protection for 6 to 12 months after birth, depending on the and antibody levels. Artificially, passive immunity is induced by administering exogenous antibodies, such as through intravenous immunoglobulin (IVIG) derived from pooled human plasma or monoclonal antibodies produced in laboratories. The mechanisms of passive immunity primarily involve antibody-mediated effects, including neutralization of or toxins to prevent their attachment to host cells, opsonization to enhance by immune cells, and activation of the for destruction. Discovered in the late 19th century by and Shibasaburo Kitasato through experiments with antitoxins, passive immunization laid the foundation for modern therapies. Clinically, passive immunity is used for immediate prophylaxis or treatment in high-risk scenarios, such as administering after wound exposure, post-bite, or monoclonal antibodies such as or to prevent (RSV) in infants. It is particularly valuable for immunocompromised individuals or during outbreaks, including the , though it does not confer immunological memory and must often be combined with active for sustained protection. Advances in production have expanded its applications to combat emerging infections and antibiotic-resistant pathogens.

Overview and mechanisms

Definition and basic principles

Passive immunity is the process by which an individual acquires immediate but temporary protection against a through the direct transfer of pre-formed antibodies from an immunized donor, without stimulating the recipient's own to produce antibodies. This form of immunity primarily involves humoral components, such as antibodies, providing short-term defense until the transferred antibodies are naturally degraded or cleared. Key characteristics of passive immunity include its transient nature, typically lasting from several weeks to three or four months, depending on the type and dose of transferred antibodies like IgG or IgA, which have varying half-lives in the body. Unlike other immune responses, it does not generate immunological memory, meaning the recipient remains susceptible to the once the borrowed protection diminishes, as no endogenous memory cells are formed. The foundational observation of passive immunity occurred in 1890, when and Shibasaburo Kitasato demonstrated that serum containing antitoxins from animals immunized against and could confer protection to uninfected animals, marking the first experimental evidence of transfer for therapeutic purposes. In comparison, active immunity arises from the recipient's direct exposure to an , which triggers the endogenous production of antibodies and the development of long-lasting memory cells, providing prolonged protection. Passive immunity can be acquired through natural or artificial means, though its mechanisms and applications vary accordingly.

Biological mechanisms of antibody transfer

Passive immunity relies primarily on the transfer of immunoglobulins, particularly IgG and IgA, from a donor to a recipient, enabling immediate protection without stimulating the recipient's adaptive . IgG is the dominant class involved in systemic passive immunity due to its ability to cross biological barriers and its extended of approximately 21 days, which allows sustained circulation in the recipient. In contrast, IgA, especially in its secretory form (sIgA), plays a key role in mucosal passive immunity, providing localized protection at epithelial surfaces such as the . The transplacental transfer of IgG occurs through an active, receptor-mediated process in the . Maternal IgG binds to the neonatal (FcRn) on the apical surface of cells via its Fc region, followed by into endosomes where pH-dependent release facilitates to the . This mechanism ensures selective transport of IgG subclasses, with IgG1 and IgG4 exhibiting higher efficiency due to stronger FcRn affinity. For IgA transfer, maternal plasma cells in the mammary glands produce dimeric IgA, which is transported across epithelial cells into and via the polymeric immunoglobulin receptor (pIgR), forming sIgA that resists proteolytic degradation in the infant's gut. Once transferred, these antibodies exert effector functions to combat in the recipient. IgG facilitates neutralization by binding to viral or bacterial antigens, preventing their attachment to host cells, and promotes opsonization by coating to enhance via Fcγ receptors on immune cells. Additionally, IgG activates the , leading to pathogen lysis and further amplification of . Secretory IgA, meanwhile, neutralizes at mucosal sites through immune exclusion, agglutinating microbes and inhibiting their to epithelial cells without triggering . In newborns receiving transplacental IgG, antibody levels typically peak at birth, reflecting maternal concentrations, and follow an curve, declining to negligible levels over 6-12 months as the 's own production matures. This waning is governed by the IgG and catabolic rates, with faster clearance observed in the early postnatal period due to immature FcRn expression in the . The efficacy of transferred depends on several physiological factors. Higher maternal antibody doses correlate with greater peak levels and prolonged in the recipient, while antibody affinity to FcRn influences transfer efficiency, with suboptimal or subclass variations reducing uptake. Recipient age at transfer impacts duration, as preterm exhibit lower absolute IgG levels due to reduced gestational exposure time. Underlying health conditions, such as placental pathologies or infant , can further impair transfer or accelerate antibody clearance, diminishing overall protective outcomes.

Natural passive immunity

Maternal passive immunity

Maternal passive immunity primarily occurs through the transplacental transfer of immunoglobulin G (IgG) antibodies from the mother's bloodstream to the fetal circulation, a process that begins as early as 13 weeks of gestation and increases linearly thereafter. This transfer is mediated by the neonatal Fc receptor (FcRn) on syncytiotrophoblast cells in the placenta, which actively transports maternal IgG across the barrier. By 28–32 weeks of gestation, fetal IgG levels reach approximately 50% of maternal concentrations, with the majority of transfer occurring in the third trimester; at term birth, fetal levels often equal or exceed maternal IgG by 100–120%, providing robust humoral protection against systemic infections. This passive immunity shields the neonate from pathogens such as tetanus and measles during the initial months of life when their own antibody production is immature. In addition to transplacental transfer, breastfeeding delivers secretory immunoglobulin A (sIgA) via and mature milk, which coats the infant's gastrointestinal mucosa to prevent adhesion and invasion by enteric pathogens. , produced in the first few days postpartum, is particularly rich in sIgA, offering localized protection against viruses like and bacteria such as and . Unlike IgG, sIgA in breast milk is resistant to proteolytic degradation in the acidic infant gut, ensuring its stability and efficacy at mucosal surfaces for immune exclusion. The duration of maternal IgG-mediated protection typically wanes after 6 months as these antibodies are gradually catabolized, with estimates around 21–28 days, leaving infants vulnerable until takes effect. This transient immunity is especially critical in regions with low vaccination coverage, where it serves as the primary defense against vaccine-preventable diseases in early infancy. Transfer efficiency varies between term and preterm infants; term neonates receive higher absolute IgG levels due to longer exposure during , while preterm infants often have reduced concentrations, increasing their susceptibility to infections. Maternal vaccination, such as a pertussis booster in the third trimester, enhances IgG levels against specific pathogens, thereby augmenting neonatal protection.

Other natural transfers

In certain avian species, such as pigeons and doves, passive immunity is transferred naturally to through , a nutrient-rich secretion produced by the epithelial lining of the parents' crop. This milk contains immunoglobulins, including IgA and IgG, which provide newborns with immediate protection against pathogens during their vulnerable early stages. Studies have demonstrated that these antibodies in are absorbed by squabs within the first day of life, contributing to immune defense against infections like . This mechanism is particularly significant in columbiform birds, where both parents produce , enhancing the transfer of maternal and paternal antibodies to support chick survival. In veterinary contexts, passive immunity via ingestion plays a vital role in , especially in species like where newborns lack transplacental transfer. Neonatal calves must consume within the first few hours after birth to absorb immunoglobulins, primarily IgG, which confer protection against common enteric pathogens such as . Failure to achieve adequate passive transfer increases the risk of scours and mortality, with studies showing that colostrum-derived antibodies control E. coli in the gut and bolster innate immune responses. This process is time-sensitive, as the calf's closes to large-molecule absorption after approximately 24 hours, limiting efficiency if delayed. These natural transfers outside typical maternal contexts are often species-specific, relying on direct or absorption mechanisms that provide short-term immunity but require timely execution for effectiveness. In non-human animals, such as birds and ruminants, they highlight adaptive strategies for neonatal protection, though they are less reliable in humans due to the dominance of placental and lactational routes.

Artificial passive immunity

Historical development

The concept of artificial passive immunity emerged in the late through pioneering experiments demonstrating that serum from immunized animals could transfer protective antibodies to treat infectious diseases. In 1890, and Shibasaburo Kitasato reported the discovery of , showing that serum from animals immunized against neutralized the pathogen's effects in animal models, marking the first successful application of serum therapy. Their work built on earlier observations of natural antibody transfer but focused on harnessing animal-derived for therapeutic use. For this breakthrough in serum therapy, particularly against , Behring was awarded the first Nobel Prize in Physiology or Medicine in 1901. Early clinical applications followed rapidly, with the first human trials of conducted in 1894 at institutions in , where 220 children received injections, achieving a of 76% compared to historical mortality exceeding 50%. Serum therapy was extended to shortly after, with introduced in clinical practice by 1891, and to by 1900, when horse-derived serum developed in reduced case fatality rates from around 20-30% to lower levels during outbreaks. These treatments proved vital during epidemics, saving thousands of lives; for instance, dramatically lowered mortality in the United States from over 40% to under 10% by the early , transforming management of these bacterial infections. Despite these successes, challenges arose from adverse reactions to animal sera, particularly horse-derived products. In 1905, Clemens von Pirquet and Béla Schick identified , an immune complex-mediated reaction characterized by fever, rash, and occurring 7-14 days after injection, affecting up to 50% of recipients in early trials. This complication prompted efforts to mitigate risks, leading to a shift toward human-derived sera in through methods like to isolate immunoglobulins from pooled human plasma, reducing foreign protein exposure. Key milestones in the mid-20th century included the 1940s development of , a concentrated immunoglobulin fraction produced via ethanol of plasma, first used successfully by Charles Janeway for measles prophylaxis, preventing severe disease in exposed children with doses of 0.1-0.25 mL/kg. Post-World War II standardization efforts, including U.S. regulatory guidelines and large-scale production from donor plasma pools, ensured safer, more consistent preparations, paving the way for broader prophylactic use against viral infections like and .

Modern applications and therapies

Intravenous immunoglobulin (IVIG) and intramuscular immunoglobulin (IMIG) are key components of modern passive immunity therapies, primarily used to treat primary immunodeficiencies and provide prophylaxis against certain infections. For patients with primary immunodeficiency diseases, IVIG is administered at replacement doses of 400–600 mg/kg body weight every 3–4 weeks to maintain adequate antibody levels and prevent recurrent infections. In cases of hepatitis A exposure, IMIG is recommended for postexposure prophylaxis at a dose of 0.1 mL/kg intramuscularly, ideally within 2 weeks of exposure, to confer immediate protection in individuals for whom vaccination is contraindicated or unavailable. Monoclonal antibodies represent a significant advancement in targeted passive immunity, offering precise and potent neutralization of pathogens. (trade name Beyfortus), approved by the FDA in July 2023, is a long-acting for preventing (RSV) lower respiratory tract disease in infants. Administered as a single intramuscular dose—50 mg for infants weighing less than 5 kg or 100 mg for those 5 kg or more—it provides protection for at least five months, covering the typical RSV season. As of 2025, CDC recommends for all infants younger than 8 months entering their first RSV season, with expanding access programs in 2024–2025. Other established applications include for and treatment of . For , human rabies immune globulin (HRIG) is given at 20 IU/kg body weight on day 0 alongside the to provide immediate neutralizing antibodies against the in unvaccinated individuals. In cases, equine-derived heptavalent is administered intravenously to neutralize circulating , reducing mortality when given early in the course of illness. During the early , monoclonal antibodies like were authorized for emergency use in mild-to-moderate cases in high-risk patients, but their efficacy has been limited by variants, leading to revocation of authorization in regions with predominant resistant strains. Emerging therapies focus on broad-spectrum monoclonal antibodies to address evolving threats from viruses like and . For , clinical trials are evaluating broadly neutralizing antibodies that target conserved viral epitopes, aiming to provide universal protection across strains with single-dose administration. Similarly, antibody cocktails such as ZMapp, composed of three monoclonal antibodies against glycoprotein, have demonstrated efficacy in preclinical and early clinical studies for and treatment, highlighting the potential for rapid deployment in outbreaks. As of 2025, new long-acting RSV monoclonal antibodies like clesrovimab are in advanced clinical trials, potentially offering alternatives to for infant prophylaxis.

Cell-mediated passive immunity

Mechanisms of T-cell transfer

Passive cell-mediated immunity is achieved through the adoptive transfer of primed T lymphocytes or cytokine-activated immune cells from a donor to a recipient, conferring immediate effector functions without requiring the recipient's own immune priming. This process, first conceptualized in the mid-20th century, enables the recipient to mount a targeted response against intracellular threats such as viruses or tumors by leveraging the transferred cells' pre-existing specificity and activation state. Donor-derived T cells for transfer are typically sourced from peripheral blood, , draining lymph nodes, or as passenger cells in allogeneic grafts. These cells are often isolated and expanded using cytokines like interleukin-2 (IL-2) to generate sufficient numbers for , ensuring they retain specificity and effector potential prior to administration. Upon transfer, the T cells home to target tissues via gradients, such as those mediated by and receptors, allowing migration to sites of or . Once at the site, transferred T cells recognize antigens presented on (MHC) molecules via their T cell receptors (TCRs), triggering activation and downstream effector responses. This includes the release of cytokines such as interferon-gamma (IFN-γ), which activates macrophages and enhances , as well as cytotoxic molecules like perforin and granzymes that directly lyse infected or malignant cells. Unlike humoral passive immunity, which relies on neutralization of extracellular pathogens, T-cell transfer primarily targets intracellular antigens through cell-mediated cytotoxicity, providing protection against threats inaccessible to antibodies. The persistence of these transferred T cells is generally short-term, lasting days to weeks, due to their effector and lack of recipient-generated , though strategies like lymphodepletion can extend this duration.

Clinical examples and limitations

One prominent clinical example of cell-mediated passive immunity is the graft-versus-tumor (GVT) effect observed in allogeneic transplants for treatment, where donor T cells transferred via recognize and eliminate residual leukemic cells. This GVT effect contributes to improved relapse-free survival in patients post-transplant, particularly when T-cell depletion is minimized to preserve donor immunity. Chimeric antigen receptor (CAR) T-cell therapy represents another key application, involving the infusion of patient-derived or donor-engineered T cells that passively confer antitumor immunity against hematologic malignancies. For instance, , approved by the FDA in 2017 for relapsed or refractory B-cell acute lymphoblastic leukemia, delivers pre-engineered CD19-targeted T cells that persist and exert cytotoxic effects without requiring active host . Clinical trials have demonstrated complete remission rates exceeding 80% in pediatric and young adult patients, highlighting its efficacy as a passive transfer mechanism. In infectious diseases, experimental T-cell transfers have been employed to combat (CMV) reactivation in transplant recipients, where donor-derived CMV-specific T cells are adoptively infused to provide immediate antiviral protection. Studies in transplant patients have shown that such transfers can resolve refractory CMV viremia with response rates up to 70%, though routine use remains limited due to logistical complexities in cell isolation and expansion. A 2025 review confirms ongoing evaluation primarily in high-risk adult cohorts, with prophylactic applications still investigational. Despite these advances, cell-mediated passive immunity faces significant limitations, including the risk of (GVHD) in allogeneic transfers, where donor T cells attack host tissues, occurring in 30-50% of cases and necessitating immunosuppressive management.31829-3/fulltext) Transferred T cells often exhibit short persistence, typically lasting weeks to months, which may require repeated dosing to maintain efficacy against persistent threats like tumors or chronic infections. High manufacturing costs, exceeding $400,000 per CAR-T infusion, restrict accessibility, compounded by the need for specialized facilities. Ethical concerns also arise in donor sourcing, such as mobilization protocols that could pose health risks to healthy volunteers. As of 2025, cell-mediated passive immunity primarily serves as an adjunct in multimodal immunotherapy regimens, such as combining CAR-T with checkpoint inhibitors for enhanced antitumor responses, rather than a standalone prophylactic strategy comparable to antibody-based approaches.

Advantages and disadvantages

Advantages

Passive immunity offers immediate protection upon antibody transfer, typically within hours, making it particularly valuable for individuals recently exposed to pathogens or those unable to mount a rapid immune response. This rapid onset contrasts with active immunity, which requires days to weeks for antibody production, allowing passive approaches to serve as an urgent intervention in high-risk scenarios. For immunocompromised patients, such as those with HIV, passive immunization provides essential short-term defense when endogenous immunity is impaired. Newborns, who receive maternal antibodies transplacentally, exemplify this benefit, gaining protection against infections before their own immune systems mature. In outbreak settings, passive immunity acts as a bridge to active immunization, delivering prompt coverage while vaccines take effect. For instance, intramuscular immunoglobulin (IG) administered within six days of measles exposure prevents or modifies disease in unvaccinated individuals, buying time for vaccination to confer long-term protection. This strategy is especially useful during epidemics, where immediate intervention can curb transmission among susceptible populations. Monoclonal antibodies (mAbs) used in passive therapy provide highly targeted protection, binding specific epitopes to neutralize threats with minimal impact on the host's normal flora. This specificity results in lower and fewer side effects compared to broad-spectrum antimicrobials, which can disrupt beneficial microbes and lead to resistance or secondary infections. For example, RSV mAbs like and, as of June 2025, clesrovimab offer precise, immediate shielding for high-risk infants without the broader disruptions of antibiotics. Passive immunity is particularly safe for vulnerable groups, such as infants and the elderly, as it involves pre-formed antibodies rather than live or attenuated pathogens, eliminating the risk of -induced disease. In infants, whose immature immune systems may not tolerate live , this approach avoids potential adverse reactions while providing critical early protection. Similarly, for elderly individuals with waning immunity, passive transfer circumvents the challenges of vaccine responsiveness without introducing risks.

Disadvantages

Passive immunity provides only temporary protection, as transferred antibodies are eventually catabolized without inducing the recipient's own or memory cells. The of (), the primary class used in passive , averages in humans, leading to a gradual decline in antibody levels and protection that typically lasts only a few weeks to months. For extended mAbs like , real-world data as of November 2025 suggest protection may extend up to 1 year, though repeat dosing may still be needed in high-risk areas. This short duration necessitates repeated administrations or boosters to maintain efficacy, unlike active immunity which establishes long-term defense. A significant drawback involves potential adverse effects, particularly from the use of (non-human) sera in early passive therapies. These can trigger allergic reactions or immune complex diseases such as , a response characterized by fever, , joint pain, and occurring 7-14 days post-administration. Although modern monoclonal antibodies (mAbs) derived from human or engineered sources have reduced these risks, remains a concern in some recipients. The high cost of producing monoclonal antibodies limits accessibility, especially in resource-constrained settings. For instance, a single dose of , a long-acting mAb for prevention in infants, costs approximately $500 in the United States, contributing to economic barriers for widespread use. While supply chain disruptions exacerbated shortages during the , for RSV mAbs, initial shortages in 2023-2024 have been addressed, with no shortages expected for 2025-2026 due to increased production and the approval of additional therapies. Passive immunity is often strain-specific, offering limited protection against viral variants due to the narrow targeting of transferred antibodies. This was evident in the , where several authorized mAbs, such as and Evusheld, lost efficacy against the variant and its sublineages, prompting the FDA to revoke or limit their emergency use authorizations.

References

  1. https://www.cdc.gov/vaccines/basics/immunity-types.html
  2. https://www.chop.edu/vaccine-education-center/human-immune-system/types-immunity
  3. https://medlineplus.gov/ency/article/000821.htm
  4. https://pmc.ncbi.nlm.nih.gov/articles/PMC7150278/
  5. https://www.ncbi.nlm.nih.gov/books/NBK539801/
  6. https://embryo.asu.edu/pages/emil-von-behring-1854-1917
  7. https://www.ncbi.nlm.nih.gov/books/NBK27162/
  8. https://www.sciencedirect.com/science/article/pii/S0092867421002208
  9. https://pmc.ncbi.nlm.nih.gov/articles/PMC8230140/
  10. https://pmc.ncbi.nlm.nih.gov/articles/PMC3251916/
  11. https://pmc.ncbi.nlm.nih.gov/articles/PMC5671757/
  12. https://pmc.ncbi.nlm.nih.gov/articles/PMC3939878/
  13. https://pmc.ncbi.nlm.nih.gov/articles/PMC6369690/
  14. https://pmc.ncbi.nlm.nih.gov/articles/PMC4159104/
  15. https://pmc.ncbi.nlm.nih.gov/articles/PMC9382412/
  16. https://pmc.ncbi.nlm.nih.gov/articles/PMC4165321/
  17. https://pmc.ncbi.nlm.nih.gov/articles/PMC5812294/
  18. https://pmc.ncbi.nlm.nih.gov/articles/PMC7098569/
  19. https://www.pnas.org/doi/10.1073/pnas.2004325117
  20. https://ascpt.onlinelibrary.wiley.com/doi/10.1111/cts.70049
  21. https://pubmed.ncbi.nlm.nih.gov/12850343/
  22. https://pmc.ncbi.nlm.nih.gov/articles/PMC11290967/
  23. https://pmc.ncbi.nlm.nih.gov/articles/PMC9463492/
  24. https://pmc.ncbi.nlm.nih.gov/articles/PMC8113393/
  25. https://www.chop.edu/vaccine-education-center/human-immune-system/development-immune-system
  26. https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247%2822%2900332-9/fulltext
  27. https://pmc.ncbi.nlm.nih.gov/articles/PMC3482181/
  28. https://journals.asm.org/doi/10.1128/CDLI.12.5.665-667.2005
  29. https://besjournals.onlinelibrary.wiley.com/doi/10.1111/j.1365-2435.2012.01988.x
  30. https://pubmed.ncbi.nlm.nih.gov/8199914/
  31. https://www.sciencedirect.com/science/article/pii/S2772694023000018
  32. https://extension.psu.edu/passive-transfer-of-immunity-and-its-impact-on-calf-health/
  33. https://pmc.ncbi.nlm.nih.gov/articles/PMC7127230/
  34. https://www.si.edu/spotlight/antibody-initiative/diphtheria
  35. https://pmc.ncbi.nlm.nih.gov/articles/PMC5347343/
  36. https://www.nobelprize.org/prizes/medicine/1901/behring/facts/
  37. https://pmc.ncbi.nlm.nih.gov/articles/PMC11752783/
  38. https://www.nobelprize.org/prizes/medicine/1901/behring/article/
  39. https://www.nytimes.com/1902/11/03/archives/a-scarlet-fever-serum.html
  40. https://academic.oup.com/ije/article/42/3/662/908858
  41. https://www.statnews.com/2017/04/26/diphtheria-new-treatment/
  42. https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%2819910915%2968:6%252B%253C1415::AID-CNCR2820681402%253E3.0.CO%3B2-0
  43. https://pmc.ncbi.nlm.nih.gov/articles/PMC4437582/
  44. https://www.jacionline.org/article/S0091-6749%2805%2901710-0/fulltext
  45. https://pmc.ncbi.nlm.nih.gov/articles/PMC1809480/
  46. https://www.cdc.gov/mmwr/volumes/66/wr/mm6636a5.htm
  47. https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-prevent-rsv-babies-and-toddlers
  48. https://www.cdc.gov/rsv/hcp/vaccine-clinical-guidance/infants-young-children.html
  49. https://www.cdc.gov/rabies/hcp/clinical-care/biologics.html
  50. https://wwwnc.cdc.gov/eid/article/8/8/01-0516_article
  51. https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-sotrovimab-emergency-use-authorization
  52. https://pmc.ncbi.nlm.nih.gov/articles/PMC12549568/
  53. https://pmc.ncbi.nlm.nih.gov/articles/PMC5568563/
  54. https://pmc.ncbi.nlm.nih.gov/articles/PMC12393692/
  55. https://www.sciencedirect.com/topics/immunology-and-microbiology/adoptive-immunity
  56. https://pmc.ncbi.nlm.nih.gov/articles/PMC6292222/
  57. https://www.jci.org/articles/view/31446
  58. https://www.nature.com/articles/s41577-020-0306-5
  59. https://www.technologynetworks.com/immunology/articles/humoral-vs-cell-mediated-immunity-344829
  60. https://pmc.ncbi.nlm.nih.gov/articles/PMC6877747/
  61. https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.00496/full
  62. https://www.cancer.gov/about-cancer/treatment/research/car-t-cells
  63. https://pmc.ncbi.nlm.nih.gov/articles/PMC8104120/
  64. https://academic.oup.com/cid/article/81/4/e218/8125789
  65. https://www.bloodresearch.or.kr/journal/view.html?uid=2590&vmd=Full
  66. https://www.mdpi.com/2076-3271/13/3/190
  67. https://www.who.int/teams/immunization-vaccines-and-biologicals/product-and-delivery-research/monoclonal-antibodies-%28mabs%29-for-infectious-diseases
  68. https://clinicalinfo.hiv.gov/en/glossary/passive-immunity
  69. https://www.cdc.gov/measles/hcp/vaccine-considerations/index.html
  70. https://www.cdc.gov/pinkbook/hcp/table-of-contents/chapter-13-measles.html
  71. https://pmc.ncbi.nlm.nih.gov/articles/PMC11858734/
  72. https://www.merck.com/news/u-s-fda-approves-mercks-enflonsia-clesrovimab-cfor-for-prevention-of-respiratory-syncytial-virus-rsv-lower-respiratory-tract-disease-in-infants-born-during-or-entering-their-fir/
  73. https://pubmed.ncbi.nlm.nih.gov/27079929/
  74. https://pmc.ncbi.nlm.nih.gov/articles/PMC7879001/
  75. https://pmc.ncbi.nlm.nih.gov/articles/PMC10537287/
  76. https://www.nature.com/articles/s41467-024-46321-9
  77. https://www.sciencedirect.com/topics/immunology-and-microbiology/passive-immunity
  78. https://www.cidrap.umn.edu/respiratory-syncytial-virus-rsv/nirsevimab-prevents-rsv-cases-young-kids-1-year-maybe-not-beyond
  79. https://historyofvaccines.org/vaccines-101/what-do-vaccines-do/passive-immunization/
  80. https://www.ncbi.nlm.nih.gov/books/NBK538312/
  81. https://emedicine.medscape.com/article/332032-overview
  82. https://medlineplus.gov/ency/article/000820.htm
  83. https://publications.aap.org/pediatrics/article/154/6/e2024068261/199958/RSV-Prevention-in-Infants-Promising-Products-But
  84. https://pmc.ncbi.nlm.nih.gov/articles/PMC7276808/
  85. https://www.aap.org/en/patient-care/respiratory-syncytial-virus-rsv-prevention/rsv-frequently-asked-questions/
  86. https://www.fda.gov/drugs/drug-safety-and-availability/fda-announces-evusheld-not-currently-authorized-emergency-use-us
  87. https://www.sciencedirect.com/science/article/pii/S1201971223006458
Add your contribution
Related Hubs
User Avatar
No comments yet.