Working group consultation: alloimmunity as a vaccine approach against HIV/AIDS: National Institutes of Health Meeting Report, May 24, 2012.

Alloimmunization vaccine strategies propose to avoid the problem of the extreme antigenic variability of human immunodeficiency virus (HIV) by instead focusing on the cellular antigens incorporated into HIV virions as they bud from infected cells. This report summarizes a Consultation meeting convened by the National Institute of Allergy and Infectious Diseases, National Institutes of Health on May 24, 2012. The objectives of the meeting were to (1) reach a consensus on the essential questions surrounding alloimmunization as a strategy for vaccine design against HIV, and (2) determine the experimental elements that might be needed for addressing these questions in an optimized pilot framework nonhuman primate (NHP) protocol for allogeneic immunization.

Rationally-designed vaccine adjuvants: separating efficacy from toxicity.

Adjuvants, substances included in many vaccines in order to improve immune responses, are challenging to develop and license because adjuvant compounds that stimulate strong protective immunity also frequently induce significant toxicity. Adjuvant design and development has until recently been largely empirical; but with the current knowledge that most adjuvants act via receptors of the innate immune system, molecular-based approaches are rapidly advancing the field. Data support the concept that proinflammatory pathways induced by innate immune receptor triggering underlie many of the observed toxic effects.

Immunology research: challenges and opportunities in a time of budgetary constraint.

There have been enormous advances in the field of immunology over the past 3 decades, and those advances have had a positive effect on many subspecialties of medicine. Opportunities for even more notable advances remain. However, present and projected budget constraints for the National Institutes of Health have created formidable challenges.

Innate immune activation as a broad-spectrum biodefense strategy: prospects and research challenges.

Biodefense strategies require protection against a broad and largely unforeseen spectrum of pathogens--the forte of innate immune system defenses--that have evolved over millennia to function within moments of encountering either ancient or newly emerging pathogens. Although constitutive, the innate immune system is activated by the presence of microbes or their products, providing a rationale for a potential biodefense strategy. Both prophylactic and postexposure strategies involving innate immune stimulation have been shown to be plausible to prevent or ameliorate infections in animal models.

Addressing parents' concerns: do vaccines cause allergic or autoimmune diseases?

Anecdotal case reports and uncontrolled observational studies in the medical literature claim that vaccines cause chronic diseases such as asthma, multiple sclerosis, chronic arthritis, and diabetes. Several biological mechanisms have been proposed to explain how vaccines might cause allergic or autoimmune diseases. For example, allergic diseases might be caused by prevention of early childhood infections (the "hygiene hypothesis"), causing a prolongation of immunoglobulin E-promoting T-helper cell type 2-type responses.

Addressing parents' concerns: do multiple vaccines overwhelm or weaken the infant's immune system?

Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines. Implicit in this concern is that the infant's immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system. In this review, we will examine the following: 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines; 2) the theoretic capacity of an infant's immune system; 3) data that demonstrate that mild or moderate illness does not interfere with an infant's ability to generate protective immune responses to vaccines; 4) how infants respond to vaccines given in combination compared with the same vaccines given separately; 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children; and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago.