Fluwatchers A Crowdsourcing Approach: Summary of the National Advisory Committee on Immunization (NACI) Seasonal Influenza Vaccine Statement for 2021–2022

BackgroundSeveral influenza vaccines are authorized in Canada and the evidence on influenza immunization is continually evolving. The National Advisory Committee on Immunization (NACI) provides recommendations regarding the use of seasonal influenza vaccines annually to the Public Health Agency of Canada (PHAC).ObjectiveTo summarize NACI recommendations regarding the use of seasonal influenza vaccines for 2021–2022 and to highlight new recommendations.MethodsAnnual influenza vaccine recommendations are developed by NACI''s Influenza Working Group for consideration and approval by NACI. The development of the recommendations is based on the NACI evidence-based process.ResultsThe following new recommendations were made: 1) Influvac^® Tetra may be considered as an option among the standard dose quadrivalent inactivated influenza vaccines (IIV4-SD) offered to adults and children three years of age and older; 2) Fluzone High Dose Quadrivalent (IIV4-HD) may be considered an option for individuals 65 years of age and older who are currently recommended to receive Fluzone^® High Dose (trivalent); and 3) Flucelvax^® Quad may be considered amongst the quadrivalent influenza vaccines offered to adults and children nine years of age and older for annual influenza immunization. Guidance for use of influenza immunizations during the coronavirus disease 2019 pandemic is also highlighted.ConclusionNACI continues to recommend that an age-appropriate influenza vaccine should be offered annually to anyone six months of age and older who does not have contraindications to the vaccine. Vaccination should be offered as a priority to people at high risk of influenza-related complications or hospitalization, people capable of transmitting influenza to those at high risk of complications, and others as indicated.     

Immunogenicity and safety of Southern Hemisphere inactivated quadrivalent influenza vaccine: a Phase III,open-label study of adults in Brazil

The World Health Organization influenza forecast now includes an influenza B strain from each of the influenza B lineages (B/Yamagata and B/Victoria) for inclusion in seasonal influenza vaccines. Traditional trivalent influenza vaccines include an influenza B strain from one lineage, but because two influenza B lineages frequently co-circulate, the effectiveness of trivalent vaccines may be reduced in seasons of influenza B vaccine-mismatch. Thus, quadrivalent vaccines may potentially reduce the burden of influenza compared with trivalent vaccines.In this Phase III, open-label study, we assessed the immunogenicity and safety of Southern Hemisphere inactivated quadrivalent influenza vaccine (Fluarix? Tetra) in Brazilian adults (NCT02369341). The primary objective was to assess hemagglutination-inhibition antibody responses against each vaccine strain 21 days after vaccination in adults (aged ≥18–60 years) and older adults (aged >60 years). Solicited adverse events for four days post-vaccination, and unsolicited adverse events and serious adverse events for 21 days post-vaccination were also assessed.A total of 63 adults and 57 older adults received one dose of inactivated quadrivalent influenza vaccine at the beginning of the 2015 Southern Hemisphere influenza season. After vaccination, in adults and older adults, the hemagglutination-inhibition titers fulfilled the European licensure criteria for immunogenicity. In adults, the seroprotection rates with HI titer ≥1:40 were 100% (A/H1N1), 98.4% (A/H3N2), 100% (B/Yamagata), and 100% (B/Victoria); in older adults were 94.7% (A/H1N1), 96.5% (A/H3N2), 100% (B/Yamagata), and 100% (B/Victoria). Pain was the most common solicited local adverse events in adults (27/62) and in older adults (13/57), and the most common solicited general adverse events in adults was myalgia (9/62), and in older adults were myalgia and arthralgia (both 2/57). Unsolicited adverse events were reported by 11/63 adults and 10/57 older adults.The study showed that inactivated quadrivalent influenza vaccine was immunogenic and well-tolerated in Brazilian adults and older adults.     

Comparative immunogenicity and cross-clade protective efficacy of mammalian cell-grown inactivated and live attenuated H5N1 reassortant vaccines in ferrets

Continued H5N1 virus infection in humans highlights the need for vaccine strategies that provide cross-clade protection against this rapidly evolving virus. We report a comparative evaluation in ferrets of the immunogenicity and cross-protective efficacy of isogenic mammalian cell-grown, live attenuated influenza vaccine (LAIV) and adjuvanted, whole-virus, inactivated influenza vaccine (IIV), produced from a clade 1 H5N1 6:2 reassortant vaccine candidate (caVN1203-Len17rg) based on the cold-adapted A/Leningrad/134/17/57 (H2N2) master donor virus. Two doses of LAIV or IIV provided complete protection against lethal homologous H5N1 virus challenge and a reduction in virus shedding and disease severity after heterologous clade 2.2.1 H5N1 virus challenge and increased virus-specific serum and nasal wash antibody levels. Although both vaccines demonstrated cross-protective efficacy, LAIV induced higher levels of nasal wash IgA and reduction of heterologous virus shedding, compared with IIV. Thus, enhanced respiratory tract antibody responses elicited by LAIV were associated with improved cross-clade protection.     

Immunogenicity and Safety of Varying Dosages of a Monovalent 2009 H1N1 Influenza Vaccine Given With and Without AS03 Adjuvant System in Healthy Adults and Older Persons

Background.?Adjuvanted vaccines have the potential to improve influenza pandemic response. AS03 adjuvant has been shown to enhance the immune response to inactivated influenza vaccines. Methods.?This trial was designed to evaluate the immunogenicity and safety of an inactivated 2009 H1N1 influenza vaccine at varying dosages of hemagglutinin with and without extemporaneously mixed AS03 adjuvant system in adults ≥18 years of age. Adults were randomized to receive 2 doses of 1 of 5 vaccine formulations (3.75?μg, 7.5?μg, or 15?μg with AS03 or 7.5?μg or 15?μg without adjuvant). Results.?The study population included 544 persons <65 years of age and 245 persons ≥65 years of age. Local adverse events tended to be more frequent in the adjuvanted vaccine groups, but severe reactions were uncommon. In both age groups, hemagglutination inhibition antibody geometric mean titers after dose one were higher in the adjuvanted groups, compared with the 15?μg unadjuvanted group, and this difference was statistically significant for the comparison of the 15?μg adjuvanted group with the 15?μg unadjuvanted group. Conclusions.?AS03 adjuvant system improves the immune response to inactivated 2009 H1N1 influenza vaccine in both younger and older adults and is generally well tolerated. ClinicalTrials.gov NCT00963157.     

Absence of cross-reactive antibodies to influenza A (H1N1) 2009 before and after vaccination with 2009 Southern Hemisphere seasonal trivalent influenza vaccine in children aged 6 months-9 years: a prospective study

Please cite this paper as: McVernon et al. (2010) Absence of cross‐reactive antibodies to influenza A (H1N1) 2009 before and after vaccination with 2009 Southern Hemisphere seasonal trivalent influenza vaccine in children aged 6 months–9 years: a prospective study. Influenza and Other Respiratory Viruses 5(1), 7–11. Background Early outbreaks of the pandemic influenza A (H1N1) 2009 virus predominantly involved young children, who fuelled transmission through spread in homes and schools. Seroprevalence studies conducted on stored serum collections indicated low levels of antibody to the novel strain in this age group, leading many to recommend priority immunisation of paediatric populations. Objectives In a prospective study, we sought evidence of cross‐reactive antibodies to the pandemic virus in children who were naïve to seasonal influenza vaccines, at baseline and following two doses of the 2009 Southern Hemisphere trivalent influenza vaccine (TIV). Patients/Methods Twenty children were recruited, with a median age of 4 years (interquartile range 3–5 years); all received two age appropriate doses of TIV. Paired sera were collected pre‐ and post‐vaccination for the assessment of vaccine immunogenicity, using haemagglutination inhibition and microneutralisation assays against vaccine‐related viruses and influenza A (H1N1) 2009. Results Robust responses to H3N2 were observed regardless of age or pre‐vaccination titre, with 100% seroconversion. Fewer seroconverted to the seasonal H1N1 component. Only two children were weakly seropositive (HI titre 40) to the pandemic H1N1 strain at study entry, and none showed evidence of seroconversion by HI assay following TIV administration. Conclusions Administration of 2009 Southern Hemisphere TIV did little to elicit cross‐reactive antibodies to the pandemic H1N1 virus in children, in keeping with assay results on stored sera from studies of previous seasonal vaccines. Our findings support the recommendations for influenza A (H1N1) 2009 vaccination of children in preparation for the 2010 winter season.     

The relative efficacy of trivalent live attenuated and inactivated influenza vaccines in children and adults

In the United States, two types of vaccines are recommended for the prevention of influenza: an intranasal live attenuated influenza vaccine (LAIV) for eligible individuals aged 2-49 years and unadjuvanted injectable trivalent inactivated vaccines (TIV) for eligible individuals aged ≥ 6 months. Several recent studies have compared the efficacy of the 2 vaccines in children and adults. In children 6 months to 18 years of age, each of the four comparative studies of LAIV and TIV demonstrated that LAIV was more protective. In individuals 17-49 years of age, most comparative studies have demonstrated that LAIV and TIV were similarly efficacious or that TIV was more efficacious. However, LAIV was shown to be more protective than TIV in new military recruits of all ages, and placebo-controlled studies in adults in 1997-1998 suggested that LAIV was more protective against the mismatched A/H3N2 strain. The relative efficacy of LAIV and TIV among young adults may vary depending on the specific population and the antigenic match between the vaccines and circulating strains. In adults 60 years of age and older, limited data suggest that the two vaccines are similarly effective. In children and adults, studies also suggest that the relative efficacy of LAIV versus TIV may increase when measured against more severe illness. Additional research comparing LAIV and TIV is needed in adults and would also be valuable in older children and adolescents. Studies should examine the role of pre-existing immunity as well as vaccine impact on influenza illness of varying severity.     

MF59®‐adjuvanted vaccines for seasonal and pandemic influenza prophylaxis

Abstract Influenza is a major cause of worldwide morbidity and mortality through frequent seasonal epidemics and infrequent pandemics. Morbidity and mortality rates from seasonal influenza are highest in the most frail, such as the elderly, those with underlying chronic conditions and very young children. Antigenic mismatch between strains recommended for vaccine formulation and circulating viruses can further reduce vaccine efficacy in these populations. Seasonal influenza vaccines with enhanced, cross‐reactive immunogenicity are needed to address these problems and can confer a better immune protection, particularly in seasons were antigenic mismatch occurs. A related issue for vaccine development is the growing threat of pandemic influenza caused by H5N1 avian strains. Vaccines against strains with pandemic potential offer the best approach for reducing the potential impact of a pandemic. However, current non‐adjuvanted pre‐pandemic vaccines offer suboptimal immunogenicity against H5N1. For both seasonal and pre‐pandemic vaccines, the addition of adjuvants may be the best approach for providing enhanced cross‐reactive immunogenicity. MF59^®, the first oil‐in‐water emulsion licensed as an adjuvant for human use, can enhance vaccine immune responses through multiple mechanisms. A trivalent MF59‐adjuvanted seasonal influenza vaccine (Fluad^®) has shown to induce significantly higher immune responses to influenza vaccination in the elderly, compared with non‐adjuvanted vaccines, and to provide cross‐reactive immunity against divergent influenza strains. Similar results have been generated with a MF59‐adjuvanted H5N1 pre‐pandemic vaccine, which showed higher and broader immunogenicity compared with non‐adjuvanted pre‐pandemic vaccines.     

Influenza A and B in a cohort of outpatient children and adolescent with influenza like-illness during two consecutive influenza seasons

IntroductionInfluenza is an important cause of morbimortality worldwide. Although people at the extremes of age have a greater risk of complications, influenza has been more frequently investigated in the elderly than in children, and inpatients than outpatients. Yearly vaccination with trivalent or quadrivalent vaccines is the main strategy to control influenza.ObjectivesDetermine the clinical and molecular characteristics of influenza A and B infections in children and adolescents with influenza-like illness (ILI).MethodsA cohort of outpatient children and adolescents with ILI was followed for 20 months. Influenza was diagnosed with commercial multiplex PCR platforms.Results179 patients had 277 episodes of ILI, being 79 episodes of influenza A and 20 episodes of influenza B. Influenza A and B cases were mild and had similar presentation. Phylogenetic tree of influenza B viruses showed that 91.6% belonged to the B/Yamagata lineage, which is not included in trivalent vaccines.ConclusionsInfluenza A and B are often detected in children and adolescents with ILI episodes, with similar and mild presentation in outpatients. The mismatch between the circulating influenza viruses and the trivalent vaccine offered in Brazil may have contributed to the high frequency of influenza A and B in this population.     

Temporal surveillance of the humoral immunity against influenza vaccine in the elderly over 9 consecutive years

BACKGROUND: The effect of age on declining immunity is well established, but its influence on humoral responses to influenza vaccines is still debated. OBJECTIVE: To compare prospectively the immunogenicity of an influenza vaccine in elderly and healthy control subjects and to search for correlations between this specific humoral protection and clinical and virological parameters. METHODS: A prospective study of the humoral response to influenza vaccine was conducted over 9 consecutive years in the long-term care units of the Saint-Etienne University Hospital, France. Antibodies directed against the vaccinal strains in an inactivated trivalent vaccine were tested by radial haemolysis before and 1 month after 477 and 242 cumulative annual vaccinations in elderly people and in healthy controls, respectively. During the last 6 years of the study, clinical samples from patients with fever > or =38 degrees C were tested systematically for the diagnosis of an influenza infection. RESULTS: A significant rise in anti-A/H3N2 antibody titres was observed in 49.3% of the elderly subjects and in 48.3% of the controls (not significant). The rises for the A/H1N1 and B strains were 31.4 and 39.2% (p < 0.001) and 30.6 and 40.5 (p < 0.001), respectively. When control subjects under 31 years old were excluded, no significant difference was recorded for any strain. Only 3.9% of the vaccinated elderly experienced any clinical influenza infection as defined by fever >/=38 degrees C and virological proof. CONCLUSIONS: The humoral response to influenza immunization is not impaired in the elderly compared with middle-aged controls, and the incidence of febrile episodes due to influenza is low in this vaccinated elderly population. These findings provide further evidence supporting the recommendation for annual influenza vaccination in the elderly.     

Influenza bei Kindern und Jugendlichen

Seasonal influenza is a cause of major morbidity in chronically ill and also healthy individuals. Besides exacerbation of chronic obstructive airway diseases there are also severe airway and extrapulmonary manifestations in otherwise healthy individuals. There is growing evidence that children are not only important transmitters of viral influenza, endangering immunodeficient individuals at risk but are also a risk group themselves. Despite clear recommendations of scientific societies, influenza immunization rates are worryingly low even in children with underlying disease conditions. Immunological features of influenza require protection at the front line. While conventional trivalent intramuscular influenza vaccines are of limited immunogenicity especially in younger children, live attenuated mucosal influenza vaccine is not only effective also in young children but the nasal application mode additionally facilitates the acceptance and performance of immunization programs. In older schoolchildren and adolescents the tetravalent intramuscular influenza vaccine is a suitable alternative with the second influenza B component considering current epidemiological aspects. It should go without saying that high immunization rates are mandatory for risk groups and health care providers as well. An additional influenza immunization of all children is a valuable contribution to the public health also encompassing those who cannot be immunized.     

Safety,efficacy, and immunogenicity of an inactivated influenza vaccine in healthy adults: a randomized,placebo-controlled trial over two influenza seasons

Background  

Seasonal influenza imposes a substantial personal morbidity and societal cost burden. Vaccination is the major strategy for influenza prevention; however, because antigenically drifted influenza A and B viruses circulate annually, influenza vaccines must be updated to provide protection against the predicted prevalent strains for the next influenza season. The aim of this study was to assess the efficacy, safety, reactogenicity, and immunogenicity of a trivalent inactivated split virion influenza vaccine (TIV) in healthy adults over two influenza seasons in the US.     

Virus-Vectored Influenza Virus Vaccines

Despite the availability of an inactivated vaccine that has been licensed for >50 years, the influenza virus continues to cause morbidity and mortality worldwide. Constant evolution of circulating influenza virus strains and the emergence of new strains diminishes the effectiveness of annual vaccines that rely on a match with circulating influenza strains. Thus, there is a continued need for new, efficacious vaccines conferring cross-clade protection to avoid the need for biannual reformulation of seasonal influenza vaccines. Recombinant virus-vectored vaccines are an appealing alternative to classical inactivated vaccines because virus vectors enable native expression of influenza antigens, even from virulent influenza viruses, while expressed in the context of the vector that can improve immunogenicity. In addition, a vectored vaccine often enables delivery of the vaccine to sites of inductive immunity such as the respiratory tract enabling protection from influenza virus infection. Moreover, the ability to readily manipulate virus vectors to produce novel influenza vaccines may provide the quickest path toward a universal vaccine protecting against all influenza viruses. This review will discuss experimental virus-vectored vaccines for use in humans, comparing them to licensed vaccines and the hurdles faced for licensure of these next-generation influenza virus vaccines.     

Superiority of live attenuated compared with inactivated influenza A virus vaccines in older, chronically ill adults

Forty-eight older adults with chronic diseases were vaccinated intranasally with live attenuated influenza A/Korea/1/82 (H3N2), CR59 virus. Forty-two (88 percent) CR59 virus recipients became infected with vaccine virus without adverse effects or change in mean pulmonary function even among the 29 infected recipients with moderate to severe chronic obstructive pulmonary disease. Among control groups who received either monovalent or trivalent inactivated influenza virus vaccines intramuscularly, the rates of fourfold rises in serum antibody titer to hemagglutinin (HA) were not different from the rate following CR59 virus inoculation. However, CR59 virus was superior to inactivated virus vaccine at stimulating secretory antibody to HA. Vaccinees age 65 years and older were more likely to shed CR59 virus in nasal secretions than were younger vaccinees, but antibody responses were not different. CR59 virus vaccine was safe and immunogenic in this population and more often induced a nasal wash IgA antibody response than the inactivated virus vaccines.     

Immunity to influenza in older adults with chronic obstructive pulmonary disease

BACKGROUND: Chronically ill older adults constitute a population vulnerable for complications associated with influenza. Study of their immunity to influenza virus may help design better strategies to stimulate protective immune responses. METHODS: Immunogenicity of influenza vaccines and immune protection from natural influenza were assessed in older adults with chronic obstructive pulmonary disease as part of a vaccine efficacy trial. Subjects received either trivalent inactivated influenza virus vaccine (TVV) intramuscularly and trivalent live cold-adapted influenza virus vaccine (CAIV-T; n=1107) intranasally (inl) or TVV and placebo inl (P; n=1108). RESULTS: In the subsets of study subjects assessed, serum hemagglutination inhibition (HAI) and nasal-wash antihemagglutinin (HA) immunoglobulin (Ig) A and IgG antibody levels and anti-influenza virus CD8(+) cytotoxic T lymphocyte activity increased after immunization. Mean postimmunization nasal-wash IgA antibody levels to influenza A H3/HA and B HA were statistically higher in the TVV+CAIV-T group (n=957) than in the TVV+P group (n=951). Postimmunization serum HAI and nasal-wash IgA antibodies to influenza A/H3N2 and B viruses were associated with a reduced relative risk for natural influenza infection. CONCLUSIONS: TVV+CAIV-T appeared more immunogenic than TVV+P, but the observed difference may be clinically unimportant. Anti-influenza serum and nasal-wash antibodies were associated with immune protection.     

Influenzaschutzimpfung

Influenza vaccination is recommended by the Standing Vaccination Committee (STIKO) at the Robert Koch Institute (RKI) for a broad range of population groups. Besides the classical inactivated trivalent split vaccine, a number of other vaccines are currently available (e.g. live attenuated vaccine, quadrivalent inactivated split vaccines, vaccines with adjuvant formulations, virosomal vaccines and intradermal injectable vaccines). The safety and tolerability of all available vaccines is generally good and serious side effects are extremely rare. The efficacy of influenza vaccination against influenza infections has been demonstrated for the majority of persons. However, effectiveness data for clinically relevant endpoints (e.g. pneumonia, hospitalization and death) are still needed.     

Influenza: epidemiology, clinical features, therapy, and prevention

Influenza A and B are important causes of respiratory illness in all age groups. Influenza causes seasonal outbreaks globally and, less commonly, pandemics. In the United States, seasonal influenza epidemics account for >200,000 hospitalizations and >30,000 deaths annually. More than 90% of deaths occur in the elderly population. Interestingly, in the novel 2009 H1N1 influenza pandemic, attack rates were highest among children and young adults. Fewer than 10% of cases occurred in adults >60 years old, likely because preexisting antibodies against other H1N1 viruses afforded protection. Despite concerns about a high lethality rate with the novel 2009 H1N1 strain, most illnesses caused by the 2009 H1N1 viruses were mild (overall case fatality rate <0.5%). Clinical features of influenza infection overlap with other respiratory pathogens (particularly viruses). The diagnosis is often delayed due to low suspicion and the limited use of specific diagnostic tests. Rapid diagnostic tests are widely available and allow detection of influenza antigen in respiratory secretions within 1 hour; however, sensitivity ranges from 50 to 90%. Neuraminidase inhibitors (NAIs) (eg, oseltamivir and zanamivir) are effective for treating influenza A or B and for prophylaxis in selected adults and children. Resistance to NAIs is rare, but influenza strains resistant to oseltamivir have been detected. Vaccines are the cornerstone of influenza control. Currently, trivalent inactivated vaccine (TIV) and live attenuated influenza vaccine (LAIV) are available. These agents reduce mortality and morbidity in high-risk patients (i.e., the elderly or patients with comorbidities), and expanding the use of vaccines to healthy children and adults reduces the incidence of influenza, pneumonia, and hospitalizations due to respiratory illnesses in the community.     

Dose-related safety and immunogenicity of a trivalent baculovirus-expressed influenza-virus hemagglutinin vaccine in elderly adults

BACKGROUND: Influenza-virus hemagglutinin (HA) protein expressed in insect cells by recombinant baculovirus is a candidate influenza vaccine. METHODS: In a randomized, double-blind trial conducted in 399 adults > or = 65 years of age, the efficacy of trivalent inactivated influenza vaccine (TIV) licensed for intramuscular injection was compared with that of trivalent baculovirus-expressed HA vaccine administered at doses of 15 microg, 45 microg, or 135 microg of each HA. RESULTS: Compared with TIV, baculovirus-expressed HA vaccine was safe and induced better serum antibody responses to the H3 component when administered at doses of 45 microg or 135 microg of each HA. CONCLUSIONS: Baculovirus-expressed HA is a safe and immunogenic influenza vaccine in elderly adults.     

Safety and immunogenicity of Sinovac’s prototype pandemic influenza H5N1 vaccines: a review on clinical trials

Abstract  Sinovac Biotech started to develop prototype pandemic influenza H5N1 vaccines in March 2004. On 2 April 2008, Sinovac’s inactivated, aluminium‐adjuvanted, whole‐virion prototype pandemic influenza A (H5N1) vaccine (PanFlu™) was granted production licensure by the China regulatory authority State Food and Drug Administration. The whole‐virion H5N1 vaccine was manufactured in embryonated hens’ eggs using the reassortant strain NIBRG‐14 (A/Vietnam/1194/2004‐A/PR/8/34) as vaccine virus. It showed good safety, immunogenicity and cross‐reactivity in immunologically naïve adults. In primed adults, the vaccine induced a strong booster response. Plasma from a vaccinated individual showed a beneficial effect following passive immunotherapy of an H5N1 human infection case. This article reviews the process, status and results of clinical evaluation of Sinovac’s whole‐ and split‐virion H5N1 vaccines by focusing on the whole‐virion vaccine.     

Current status of live attenuated influenza vaccine in the United States for seasonal and pandemic influenza

Abstract A live attenuated influenza vaccine (LAIV) is currently approved in the United States for the prevention of influenza in individuals 2–49 years of age. This article summarizes the available data describing the safety and efficacy of LAIV for the prevention of influenza in both children and adults. LAIV is administered as an intranasal spray and has been shown to provide high levels of efficacy against influenza illness caused by both matched and mismatched strains in children and adults. In studies comparing LAIV and inactivated influenza vaccine in children, LAIV recipients experienced 35–53% fewer cases of culture‐confirmed influenza illness caused by antigenically matched strains. Protection through a second influenza season against antigenically matched strains has also been seen in children. In adults, definitive comparative studies of LAIV and inactivated vaccine have not been conducted and no statistically significant differences in efficacy have been demonstrated. The most common adverse reactions with LAIV include runny nose/nasal congestion in all age groups, fever >100°F in children, and sore throat in adults. Formulations of LAIV against pandemic influenza strains, including H5N1, H9N2, and H7N3, are currently being tested in preclinical and phase I clinical studies.     

Comparison of live, attenuated H1N1 and H3N2 cold-adapted and avian-human influenza A reassortant viruses and inactivated virus vaccine in adults

The infectivity, immunogenicity, and efficacy of live, attenuated influenza A/Texas/1/85 (H1N1) and A/Bethesda/1/85 (H3N2) avian-human (ah) and cold-adapted (ca) reassortant vaccines were compared in 252 seronegative adult volunteers. The immunogenicity and efficacy of the H1N1 reassortant vaccine were also compared with those of the trivalent inactivated virus vaccine. Each reassortant vaccine was satisfactorily attenuated. The 50% human infectious dose was 10(4.9) for ca H1N1, 10(5.4) for ah H1N1, 10(6.4) for ca H3N2, and 10(6.5) TCID50 for ah H3N2 reassortant virus. Within a subtype, the immunogenicities of ah and ca vaccines were comparable. Five to seven weeks after vaccination, volunteers were challenged with homologous wild-type influenza A virus. The magnitude of shedding of virus after challenge was greater than 100-fold less in H1N1 vaccinees and greater than 10-fold less in H3N2 vaccinees compared with unimmunized controls. The vaccines were equally efficacious, as indicated by an 86%-100% reduction in illness. Thus, the ah A/Mallard/New York/6750/78 and the ca A/Ann Arbor/6/60 reassortant viruses are comparable.