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Immunisation during pregnancy is a relatively new strategy, and is currently limited to tetanus, pertussis, and influenza vaccines. None of these vaccines were developed specifically for use in pregnancy, but they provide an effective method of protecting mothers and young infants. In response to increases in pertussis morbidity and mortality among young infants, several countries have recommended universal tetanus, diphtheria, and acellular pertussis immunisation during pregnancy. Similarly, many countries recommend influenza immunisation during pregnancy to reduce the risk of disease for mother and infant. Although scientific evidence to support maternal immunisation against pertussis and influenza is rapidly accumulating, important knowledge gaps remain that need to be addressed by future research, which we have highlighted in this Series paper.

The risk and severity of specific infections are increased during pregnancy due to a combination of physiological and immunological changes. Characterizing the maternal immune system during pregnancy is important to understand how the maternal immune system maintains tolerance towards the allogeneic fetus. This may also inform strategies to prevent maternal fatalities due to infections and optimize maternal vaccination to best protect the mother-fetus dyad and the infant after birth. In this review, we describe what is known about the immunological changes that occur during a normal pregnancy.

Respiratory syncytial virus (RSV) causes a spectrum of respiratory illnesses in infants and young children that may lead to hospitalizations and a substantial number of outpatient visits, which result in a huge economic and healthcare burden. Most hospitalizations happen in otherwise healthy infants, highlighting the need to protect all infants against RSV. Moreover, there is evidence on the association between early-life RSV respiratory illness and recurrent wheezing/asthma-like symptoms As such, RSV is considered a global health priority. However, despite this, the only prevention strategy currently available is palivizumab, a monoclonal antibody (mAb) indicated in a subset of preterm infants or those with comorbidities, hence leaving the majority of the infant population unprotected against this virus. Therefore, development of prevention strategies against RSV for all infants entering their first RSV season constitutes a large unmet medical need. The aim of this review is to explore different immunization approaches to protect all infants against RSV. Prevention strategies include maternal immunization, immunization of infants with vaccines, immunization of infants with licensed mAbs (palivizumab), and immunization of infants with long-acting mAbs (e.g., nirsevimab, MK-1654). Of these, palivizumab use is restricted to a small population of infants and does not offer a solution for all-infant protection, whereas vaccine development in infants has encountered various challenges, including the immaturity of the infant immune system, highlighting that future pediatric vaccines will most likely be used in older infants (>6 months of age) and children. Consequently, maternal immunization and immunization of infants with long-acting mAbs represent the two feasible strategies for protection of all infants against RSV. Here, we present considerations regarding these two strategies covering key areas which include mechanism of action, “consistency” of protection, RSV variability, duration of protection, flexibility and optimal timing of immunization, benefit for the mother, programmatic implementation, and acceptance of each strategy by key stakeholders. We conclude that, based on current data, immunization of infants with long-acting mAbs might represent the most effective approach for protecting all infants entering their first RSV season.

As placental mammals, the pregnant women and the fetus have intense and prolonged interactions during gestation. There is increasing evidence that multiple molecular as well as cellular components originating in pregnant women are transferred to the fetus. The transfer of maternal antibodies has long been recognized as a central component of newborn immunity against pathogens. More recent studies indicate that inflammatory mediators, micronutrients, microbial products and maternal cells are transferred in utero and influence the fetal immune system. Together, these multiple signals are likely to form a complex network of interactions that program the neonatal immune system and tune its homeostatic regulation. Maternal disorders, in particular infectious diseases, modify these signals and may thereby alter immunity in early life. Understanding maternal programming of the newborn immune system could provide a basis for interventions promoting child health.

An effective vaccine against SARS-CoV-2 will reduce morbidity and mortality and allow substantial relaxation of physical distancing policies. However, the ability of a vaccine to prevent infection or disease depends critically on protecting older individuals, who are at highest risk of severe disease. We quantitatively estimated the relative benefits of COVID-19 vaccines, in terms of preventing infection and death, with a particular focus on effectiveness in elderly people. We applied compartmental mathematical modelling to determine the relative effects of vaccines that block infection and onward transmission, and those that prevent severe disease. We assumed that vaccines showing high efficacy in adults would be deployed, and examined the effects of lower vaccine efficacy among the elderly population. Our mathematical model was calibrated to simulate the course of an epidemic among the entire population of British Columbia, Canada. Within our model, the population was structured by age and levels of contact. We assessed the effectiveness of possible vaccines in terms of the predicted number of infections within the entire population, and deaths among people aged 65 years and over. In order to reduce the overall rate of infections in the population, high rates of deployment to all age groups will be critical. However, to substantially reduce mortality among people aged 65 years and over, a vaccine must directly protect a high proportion of people in that group. Effective vaccines deployed to a large fraction of the population are projected to substantially reduce infection in an otherwise susceptible population. However, even if transmission were blocked highly effectively by vaccination of children and younger adults, overall mortality would not be substantially reduced unless the vaccine is also directly protective in elderly people. We strongly recommend: (i) the inclusion of people aged 65 years and over in future trials of COVID-19 vaccine candidates; (ii) careful monitoring of vaccine efficacy in older age groups following vaccination.

Infants born to human immunodeficiency virus (HIV) infected women are HIV-exposed but the majority remains uninfected [i.e., HIV-exposed uninfected (HEU)]. HEU infants suffer greater morbidity and mortality from infections compared to HIV-unexposed (HU) peers. The reason(s) for these worse outcomes are uncertain, but could be related to an altered immune system state. This review comprehensively summarizes the current literature investigating the adaptive and innate immune system of HEU infants. HEU infants have altered cell-mediated immunity, including impaired T-cell maturation with documented hypo- as well as hyper-responsiveness to T-cell activation. And although prevaccination vaccine-specific antibody levels are often lower in HEU than HU, most HEU infants mount adequate humoral immune response following primary vaccination with diphtheria toxoid, type b, whole cell pertussis, measles, hepatitis B, tetanus toxoid, and pneumococcal conjugate vaccines. However, HEU infants are often found to have lower absolute neutrophil counts as compared to HU infants. On the other hand, an increase of innate immune cytokine production and expression of co-stimulatory markers has been noted in HEU infants, but this increase appears to be restricted to the first few weeks of life. The immune system of HEU children beyond infancy remains largely unexplored.

•Timing of gestational Tdap immunization might optimize pertussis control.•Tdap immunization at 27–30+6 weeks gestation provides the newborns highest PT IgG.•Tdap immunization at 27–30+6 weeks gestation provides the newborns highest FHA IgG.•Tdap immunization 8–12 weeks prior to delivery provides the newborns highest PT IgG.•Tdap immunization 8–12 weeks prior to delivery provides the newborns highest FHA IgG. The Centers for Disease Control and Prevention recommend Tdap immunization during pregnancy, preferably at 27–36 weeks. To ascertain whether there is a preferential period of maternal Tdap immunization during pregnancy that provides the highest concentration of pertussis-specific antibodies to the newborn. This prospective study measured pertussis-specific antibodies in paired maternal-cord sera of women immunized with Tdap after the 20th week of their pregnancy (n=61). The geometric mean concentrations (GMCs) of Immunoglobulin G (IgG) to pertussis toxin (PT) were higher in the newborns’ cord sera when women were immunized at 27–30+6 weeks (n=21) compared with 31–36 weeks (n=30) and >36 weeks (n=7), 46.04 international units/milliliter (IU/mL) (95% CI, 24.29–87.30) vs. 8.69IU/mL (95% CI, 3.66–20.63) and 21.12IU/mL (95% CI, 7.93–56.22), p<0.02, respectively. The umbilical cord GMCs of IgG to filamentous hemagglutinin (FHA) were higher in the newborns’ cord sera when women were immunized at 27–30+6 weeks compared with 31–36 weeks and >36 weeks, 225.86IU/mL (95% CI, 182.34–279.76) vs. 178.31IU/mL (95% CI, 134.59–237.03) and 138.03IU/mL (95% CI, 97.61–195.16), p<0.02, respectively. Immunization of pregnant women with Tdap between 27–30+6 weeks was associated with the highest umbilical cord GMCs of IgG to PT and FHA compared with immunization beyond 31 weeks gestation. Further research should be conducted to reaffirm these finding in order to promote an optimal pertussis controlling policy.

Respiratory syncytial virus (RSV) is a common virus that can cause serious infections in newborns and infants, especially those with certain risk factors. Until recently, the only intervention available to prevent RSV in infants was palivizumab, but its use has been limited. However, a new intervention called nirsevimab has been approved in Canada. Nirsevimab is a long-acting monoclonal antibody that prevents RSV infection by blocking the virus's entry. It has been shown to be highly effective in reducing the risk of RSV infection, hospital admissions, and severe RSV disease. Nirsevimab is safe and well-tolerated, with minimal side effects. It is recommended for infants up to 24 months of age, particularly those at high risk. Nirsevimab programs are being implemented in various countries, and its use is expected to replace palivizumab for high-risk infants. However, the availability and implementation of nirsevimab programs vary across different regions.

Maternal vaccination against respiratory syncytial virus (RSV) during pregnancy can protect infants from RSV infection. The RSVpreF vaccine, given to pregnant women, boosts maternal RSV antibodies that are transferred to the baby, providing protection for up to 6 months after birth. In a randomized controlled trial, RSVpreF significantly reduced severe lower respiratory tract infections, RSV infections requiring healthcare visits, and hospital admissions for RSV in infants. Health Canada has authorized RSVpreF vaccination between 32-36 weeks gestation to mitigate the risk of preterm delivery. The overall safety of RSV vaccination in pregnancy has been supported by studies, with rates of serious adverse events similar between vaccinated and placebo groups. RSVpreF is considered an acceptable alternative to nirsevimab, a monoclonal antibody recommended for infants at birth. Maternal vaccination offers a promising strategy to protect infants from RSV infection.