Passive Immunity

Introduction

Immunization is the process of inducing immunity against a specific disease. Immunity can be acquired actively or passively. Passive immunity is achieved by the administration of preformed antibodies, rather than stimulating the host's immune system to produce its own antibodies (active immunity).

The key characteristics of passive immunity are:

• Immediate Protection: It provides immediate protection upon administration, which is critical in post-exposure scenarios or for pathogens with rapid disease progression.
• Transient Nature: Unlike active immunity, passive immunity does not generate immunologic memory. Protection is temporary, lasting only weeks to months as the transferred antibodies are catabolized.

Types of Passive Immunity

1. Natural Passive Immunity:

   • Transplacental: Transfer of maternal IgG antibodies to the fetus, providing protection during the first few months of life.
   • Breastfeeding: Transfer of secretory IgA and other factors to the infant via breast milk, protecting mucosal surfaces.

2. Artificial Passive Immunity:

   • Achieved through the administration of antibody-containing preparations derived from humans, animals, or recombinant technology.

Preparations Used for Passive Immunization

Clinical products available for passive immunization fall into four main categories:

1. Standard Human Immunoglobulins (IG): Derived from pooled human plasma.
   • Intramuscular (IMIG)
   • Intravenous (IVIG)
   • Subcutaneous (SCIG)
2. Hyperimmune Globulins: Preparations with high antibody titers against specific pathogens, derived from donors with high levels of specific antibodies.
3. Animal Antisera (Heterologous): Derived from animals (usually horses). Requires caution due to the risk of serum sickness and anaphylaxis.
4. Monoclonal Antibodies (mAbs): Produced by recombinant DNA technology against a single antigen.

Clinical Applications in Pediatrics

The clinical applications of passive immunity in pediatrics are broad, categorized primarily into replacement therapy, prophylaxis (pre- and post-exposure), and treatment of specific diseases.

1. Replacement Therapy for Immunodeficiencies

For children with defects in antibody production (e.g., X-linked Agammaglobulinemia, Common Variable Immunodeficiency), passive immunization is life-saving.

• IVIG or SCIG: Used to maintain adequate serum IgG levels to prevent recurrent bacterial infections.
• Secondary Immunodeficiencies: IVIG is also indicated for hypogammaglobulinemia associated with pediatric HIV infection or B-cell malignancies (e.g., CLL).

2. Prophylaxis Against Infectious Diseases

Passive immunity is crucial for preventing infection after exposure (Post-Exposure Prophylaxis - PEP) or before exposure in high-risk infants.

• Respiratory Syncytial Virus (RSV):
  • Palivizumab: A monoclonal antibody used for prophylaxis in high-risk infants (prematurity, chronic lung disease, congenital heart disease).
  • Nirsevimab: A newer long-acting monoclonal antibody recommended for all infants entering their first RSV season.
• Hepatitis B:
  • HBIG: Administered to neonates born to HBsAg-positive mothers (along with the Hep B vaccine) within 12 hours of birth to prevent perinatal transmission.
• Varicella (Chickenpox):
  • VariZIG: Indicated for high-risk susceptible individuals exposed to varicella (e.g., immunocompromised children, pregnant women, newborns whose mothers developed varicella 5 days before to 2 days after delivery, and hospitalized preterms <28 weeks).
• Measles:
  • IMIG/IVIG: Administered to susceptible contacts (especially infants <6 months and immunocompromised children) within 6 days of exposure to prevent or modify the disease.
• Tetanus and Rabies:
  • Tetanus IG (TIG) and Rabies IG (RIG) are essential components of wound management and PEP, respectively, to neutralize toxins or virus before they enter the nervous system.

3. Treatment of Infectious and Inflammatory Diseases

Passive immunity is used therapeutically to neutralize toxins or modulate the immune response.

• Kawasaki Disease & MIS-C: High-dose IVIG is the standard of care to reduce systemic inflammation and prevent coronary artery aneurysms in Kawasaki disease and Multisystem Inflammatory Syndrome in Children (MIS-C).
• Botulism:
  • BabyBIG (Human Botulism IG): Used specifically for the treatment of infant botulism to neutralize circulating neurotoxin.
  • Heptavalent Botulinum Antitoxin: Equine-derived, used for non-infant botulism.
• Diphtheria: Equine Diphtheria Antitoxin is used to neutralize the exotoxin in suspected cases.
• Immune Thrombocytopenia (ITP): IVIG is used to rapidly increase platelet counts in acute ITP by blocking Fc receptors on macrophages.

Precautions and Limitations

• Interference with Live Vaccines: Passively acquired antibodies can neutralize live-attenuated vaccines (e.g., Measles, Varicella). Vaccination should generally be delayed for 3–11 months after IG administration, depending on the dose.
• Hypersensitivity: Anaphylactic reactions may occur, particularly in patients with IgA deficiency receiving products containing IgA.
• Serum Sickness: A risk associated with the use of animal-derived antisera (e.g., diphtheria antitoxin).