The “Cocooning Vaccination” Strategy as a Method of Preventing Infant Infection

The cocooning vaccination strategy involves vaccinating individuals in close contact with infants (up to 12 months of age) who cannot be vaccinated due to age restrictions, contraindications to vaccination, or precautions.

The goal is to minimize the risk of transmission of pathogens in the susceptible infant’s environment by reducing the likelihood of disease development in the immunized.

Epidemiology

About half of infants diagnosed with whooping cough require hospitalization. The most severe complications of whooping cough (pneumonia, apnea, atelectasis, emphysema, and encephalitis) are more common in newborns and infants; about 75% of whooping cough-related deaths occur in infants under 3 months of age.

Children under 6 months are at the highest risk of influenza infection and associated hospitalizations and fatalities (hospitalization rates for healthy infants are similar to those for high-risk adults).

Infants under 6 months and children with one or more comorbidities are at higher risk of severe COVID-19. Hospitalization rates for children in the first half of life are higher than in any other age group of children and are comparable to those among adults aged 65 and older.

Respiratory syncytial virus (RSV) is the main pathogen (about 68% of cases) of lower respiratory tract infections (LRTI) in infants and accounts for 2–3% of their hospitalizations.

Relevance

Difficulties in developing vaccines for newborns are due to ethical complexities of conducting clinical trials at this age and less effective immune responses to a number of vaccines compared to older children and adults.

The American Academy of Pediatrics, the American College of Obstetricians and Gynecologists, the World Health Organization, the Centers for Disease Control and Prevention (CDC), and the Advisory Committee on Immunization Practices (ACIP) in the USA recommend vaccination of pregnant women against tetanus, whooping cough, influenza, COVID-19, and RSV. The recommended vaccines significantly reduce the incidence of disease and related complications in infants.

Vaccination against whooping cough is allowed for children from the age of 6-8 weeks, with 3 doses of the vaccine necessary for adequate protection. Influenza and COVID-19 vaccinations are approved for children aged ≥6 months. The severity of flu seasons and COVID-19 is always unpredictable. The hospitalization rate for infants under 6 months for flu is 125–375 per 100,000 people, and the mortality rate is 0.73 per 100,000 cases. Chickenpox vaccines are approved from 9 months, while measles, rubella, and mumps vaccines are approved from 1 year of age. In resource-limited settings, neonatal tetanus mortality can reach 80–100%.

During the critical period before the start of primary immunization of infants, vaccination of pregnant women and close contacts is a safe and effective tool to reduce perinatal morbidity and mortality from vaccine-preventable infectious diseases.

Background

Studies have demonstrated high efficacy of vaccination of pregnant women in reducing the risk of severe infections in infants:

• Whooping cough: reduction in confirmed cases by up to 91% in infants under 3 months and up to 69% in those up to 1 year;
• Influenza: reduction in confirmed cases by 30–63% in children under 6 months;
• Respiratory syncytial viral infection (RSV): reduction in the risk of severe lower respiratory tract infections by 82% in infants up to 3 months;
• COVID-19: depending on the circulating strain, the effectiveness in reducing hospitalizations was up to 52% and ICU admissions by up to 70% in children under 6 months.
• Tetanus: reduction in neonatal tetanus cases and mortality worldwide by 88% and 94%, respectively.

Long-term studies on the safety of maternal vaccination consistently demonstrate no association with any increased risk of adverse pregnancy outcomes or neonatal complications.

Pregnancy testing before live vaccination is not required. Although live vaccine instructions (against measles, rubella, mumps, or chickenpox) recommend postponing pregnancy by 3 months post-vaccination, the CDC and ACIP recommend postponing attempts to conceive for 4 weeks. These recommendations are based on the exclusion of theoretical risk to the fetus, since no adverse pregnancy or fetal development outcomes have been registered to date as a result of vaccination against measles, rubella, mumps, chickenpox shortly before or early in pregnancy (such inadvertent vaccination is not grounds for termination of pregnancy).

Live vaccines can be administered at any time postpartum to susceptible mothers regardless of breastfeeding (including within the first 24 hours after delivery).

Immunization of the pregnant woman as part of the “cocooning vaccination” strategy

Transplacental transfer of antibodies

Vaccines administered during pregnancy induce the production of antigen-specific antibodies, which are transmitted transplacentally to the fetus. The predominant isotype is IgG.

Passive immunization through maternal antibody transmission provides the infant with a diverse range of antigen-specific antibodies during the critical postpartum period, with a half-life ranging from 28 to 35 days.

Please be aware that lysis of maternal antibodies occurs in many infants by the age of 3 months.

Factors influencing the level of transmitted antibodies

The concentration of maternal IgG transmitted to the fetus depends on several factors, including gestational age and birth weight.

Dynamics of IgG accumulation in cord blood:

• By 12–22 weeks — about 10% of the maternal level;
• By the end of the second trimester — about 50%;
• In the third trimester IgG levels increase significantly.

Vaccination after 32–34 weeks of pregnancy results in less antibody transmission due to insufficient time for their synthesis and transfer to the fetus.

Transmission of antibodies through breast milk

Vaccination during pregnancy and the postpartum period also provides transmission of antibodies (IgA is a predominant isotype) to the mucous membrane of the infant’s respiratory and gastrointestinal tracts via breast milk.

Maternal antibodies are endocytosed by mammary epithelial cells, followed by secretion into colostrum and breast milk.

Immune cocoon

Below are the main infectious diseases for which prevention is a key element of the immune cocoon strategy.

COVID-19

• Pregnant women: 1 dose of any vaccine appropriate for age and seasonal composition, at any gestational age. Those vaccinated in the current season before pregnancy do not require an additional dose.
• All contacts: with vaccines appropriate for age according to a clinical decision made jointly, emphasizing that the risk-benefit of vaccination is most favorable for those at high risk of severe COVID-19*, and least for those not at increased risk.

Explanations:

* Associated conditions and increased risk of severe course of COVID-19

Influenza

Age ≥6 months (including the pregnant woman): annual seasonal influenza vaccination with any age- and health status-appropriate vaccine.

Whooping cough

• Pregnant women: 1 dose of Tdap in each pregnancy, preferably at gestational ages 27–36 weeks (transferred maternal antibody concentration is highest when immunization is done within these terms, but it can be administered at any time during pregnancy).
• All unvaccinated or incompletely vaccinated contacts: complete a 3-dose primary series with recommended minimal intervals and a booster Tdap based on age.

Tdap = diphtheria (with reduced antigen content) and tetanus toxoids adsorbed, combined with an acellular pertussis component.

Respiratory syncytial virus

Pregnant women of any age regardless of RSV history at 32 weeks and 0 days to 36 weeks and 6 days of gestation : 1 dose of Abrysvo during the RSV season (often September to January in Northern Hemisphere countries, but it may vary regionally from year to year). Should not be administered at the 37th week of pregnancy and later, and less than 2 weeks before delivery. If gestational age meets the criteria, but there is a likelihood of delivery within 2 weeks, it is advisable to postpone vaccination and plan the immunization of the newborn with monoclonal antibodies against RSV.

Vaccination is not recommended for all other pregnant women. There is no data on whether vaccination is indicated in each pregnancy. Measles, rubella, mumps, chickenpox.

All contacts without evidence of immunity or partially immunized: complete primary series according to age and recommended minimal intervals.

Evidence of immunity:

• Presence of medical records confirming vaccination;
• Laboratory evidence of immunity;
• Laboratory evidence of measles, mumps, or rubella disease (diagnosis without laboratory confirmation is not evidence of immunity);
• A history of chickenpox or shingles.

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Conclusions

Based on clinical and epidemiological data, the following factors affecting the effectiveness of “cocooning vaccination” can be formulated:

• Universal vaccination of individuals in the immediate environment of the child (relatives and all caregivers) when there are no contraindications; optimal vaccination timing is at least 3-4 weeks before the anticipated contact with the child;
• Not limited only to families with children from risk groups;
• The strategy is a comprehensive approach rather than the sole element of infectious disease prevention.